Published papers

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).

A considerable number of patients with mild traumatic brain injury have been known to ‘‘talk and die.’’ Serial neurological examinations, however, have been the only method of determining the necessity of repeat computed tomography (CT), and no validated method has been available to predict early deterioration of minor head injury. This study aimed to evaluate the association between hypertension and bradycardia, a classic sign of raised intracranial pressure (Cushing reflex) on hospital arrival and determine the clinical consequences of minor head injury after blunt trauma. We created a new Cushing Index (CI) by dividing the systolic blood pressure by the heart rate (equaling the inverse number of the Shock Index, a score for hemodynamic stability) and hypothesized that a high CI would predict surgical intervention for deterioration and in-hospital death among patients with minor head injury. To test our hypothesis, a retrospective observational study was conducted using a nationwide trauma database. Accordingly, adult blunt trauma with minor head injury (defined as a Glasgow Coma Scale of 13–15 and Abbreviated Injury Scale score of ‡2 in the head) who were transported directly from the scene by ambulances were included. Among the 338,744 trauma patients identified in the database, 38,844 were eligible for inclusion. A restricted cubic spline regression curve for risks of in-hospital death was created using the CI. Thereafter, the thresholds were determined based on inflection points of the curve, and patients were divided into low-, intermediate-, and high-CI groups. Patients with high CI showed significantly higher in-hospital mortality rates compared with those with intermediate CI (351 [3.0%] vs. 373 [2.3%]; odds ratio [OR] = 1.32 [1.14–1.53]; p < 0.001). Patients with high index also had a higher incidence of emergency cranial surgery within 24h after arrival than those with an intermediate CI (746 [6.4%] vs. 879 [5.4%]; OR = 1.20 [1.08–1.33]; p < 0.001). In addition, patients with low CI (equal to high Shock Index, meaning hemodynamically unstable) showed higher in-hospital death compared with those with intermediate CI (360 [3.3%] vs. 373 [2.3%]; p < 0.001). In conclusion, a high CI (high systolic blood pressure and low heart rate) on hospital arrival would be helpful in identifying patients with minor head injury who might experience deterioration and need close observation.

Background: Some academic organizations recommended that physicians intubate patients with COVID-19 with a relatively lower threshold of oxygen usage particularly in the early phase of pandemic. We aimed to elucidate whether early intubation is associated with decreased in-hospital mortality among patients with novel coronavirus disease 2019 (COVID-19) who required intubation. Methods: A multicenter, retrospective, observational study was conducted at 66 hospitals in Japan where patients with moderate-to-severe COVID-19 were treated between January and September 2020. Patients who were diagnosed as COVID-19 with a positive reverse-transcription polymerase chain reaction test and intubated during admission were included. Early intubation was defined as intubation conducted in the setting of ≤ 6 L/min of oxygen usage. In-hospital mortality was compared between patients with early and non-early intubation. Inverse probability weighting analyses with propensity scores were performed to adjust patient demographics, comorbidities, hemodynamic status on admission and time at intubation, medications before intubation, severity of COVID-19, and institution characteristics. Subgroup analyses were conducted on the basis of age, severity of hypoxemia at intubation, and days from admission to intubation. Results: Among 412 patients eligible for the study, 110 underwent early intubation. In-hospital mortality was lower in patients with early intubation than those with non-early intubation (18 [16.4%] vs. 88 [29.1%]; odds ratio, 0.48 [95% confidence interval 0.27–0.84]; p = 0.009, and adjusted odds ratio, 0.28 [95% confidence interval 0.19–0.42]; p < 0.001). The beneficial effects of early intubation were observed regardless of age and severity of hypoxemia at time of intubation; however, early intubation was associated with lower in-hospital mortality only among patients who were intubated later than 2 days after admission. Conclusions: Early intubation in the setting of ≤ 6 L/min of oxygen usage was associated with decreased in-hospital mortality among patients with COVID-19 who required intubation. Trial Registration None.

Background: Intestinal microinflammation with immune dysfunction due to severe acute respiratory syndrome coronavirus 2 reportedly precipitates post-infectious irritable bowel syndrome. This study aimed to elucidate potential risk factors for subsequent development of irritable bowel syndrome, hypothesizing that it is associated with specific symptoms or patient backgrounds. Methods: This single-center retrospective observational study (2020–2021) included adults with confirmed coronavirus disease requiring hospital admission and was conducted using real-world data retrieved from a hospital information system. Patient characteristics and detailed gastrointestinal symptoms were obtained and compared between patients with and without coronavirus disease-induced irritable bowel syndrome. Multivariate logistic models were used to validate the risk of developing irritable bowel syndrome. Moreover, daily gastrointestinal symptoms during hospitalization were examined in patients with irritable bowel syndrome. Results: Among the 571 eligible patients, 12 (2.1%) were diagnosed with irritable bowel syndrome following coronavirus disease. While nausea and diarrhea during hospitalization, elevated white blood cell count on admission, and intensive care unit admission were associated with the development of irritable bowel syndrome, nausea and diarrhea were identified as risk factors for its development following coronavirus disease, as revealed by the adjusted analyses (odds ratio, 4.00 [1.01–15.84] and 5.64 [1.21–26.31], respectively). Half of the patients with irritable bowel syndrome had both diarrhea and constipation until discharge, and constipation was frequently followed by diarrhea. Conclusions: While irritable bowel syndrome was rarely diagnosed following coronavirus disease, nausea and diarrhea during hospitalization precede the early signs of irritable bowel syndrome following coronavirus disease.

STUDY OBJECTIVE: To elucidate the clinical utility of the Clinical Frailty Scale score for predicting poor neurologic functions in patients resuscitated from out-of-hospital cardiac arrest (OHCA). METHODS: This was a prospective, multicenter, observational study conducted between 2019 and 2021. The study included adults with nontraumatic OHCA admitted to the intensive care unit after return of spontaneous circulation (ROSC). Pre-arrest high Clinical Frailty Scale score was defined as 5 or more. Favorable neurologic outcomes defined as a Cerebral Performance Category score of 2 or less at 30 days after admission were compared between patients with and without high Clinical Frailty Scale scores. Multivariable logistic regression analyses fitted with generalized estimating equations were performed to adjust for patient characteristics, out-of-hospital information, and resuscitation content and account for within-institution clustering. RESULTS: Of 9,909 patients with OHCA during the study period, 1,216 were included, and 317 had a pre-arrest high Clinical Frailty Scale score. Favorable neurologic outcomes were fewer among patients with high Clinical Frailty Scale scores. The high Clinical Frailty Scale score group showed a lower percentage of favorable neurologic outcomes after OHCA than the low Clinical Frailty Scale score group (6.1% vs 24.4%; adjusted odds ratio, 0.45 [95% confidence interval 0.22 to 0.93]). This relationship remained in subgroups with cardiogenic OHCA, with ROSC after hospital arrival, and without a high risk of dying (Clinical Frailty Scale score of 7 or less), whereas the neurologic outcomes were comparable regardless of pre-arrest frailty in those with noncardiogenic OHCA and with ROSC before hospital arrival. CONCLUSIONS: Pre-arrest high Clinical Frailty Scale score was associated with unfavorable neurologic functions among patients resuscitated from OHCA. The Clinical Frailty Scale score would help predict clinical consequences following intensive care after ROSC.

Purpose: Vital signs are important for predicting clinical outcomes in patients with trauma. However, their accuracy can be affected in older adults because hemodynamic changes are less obvious. This study aimed to examine the usefulness of changes in vital signs during transportation in predicting the need for hemostatic treatments in older patients with trauma. Methods: This retrospective cohort study was conducted using data from the Japan Trauma Data Bank (2004–2019). Patients aged ≥ 65 years who were hemodynamically stable at the scene were included in this study. The incidence of emergency surgery within 12 h after hospital arrival was compared between patients with delta Shock Index (dSI) > 0.1 and those with dSI ≤ 0.1. Predicting ability was examined after adjusting for patient demographics, comorbidities, vital signs at the scene and on hospital arrival, Injury Severity Score, and abbreviated injury scale in each region. Results: Among the 139,242 patients eligible for the study, 3,701 underwent urgent hemostatic surgery within 12 h. Patients with dSI > 0.1 showed a significantly higher incidence of emergency surgery than those with dSI ≤ 0.1 (871/16,549 [5.3%] vs. 2,830/84,250 [3.4%]; odds ratio (OR), 1.60 [1.48–1.73]; adjusted OR, 1.22 [1.08–1.38]; p = 0.001). The relationship between high dSI and a higher incidence of intervention was observed in patients with hypertension and those with decreased consciousness on arrival. Conclusion: High dSI > 0.1 was significantly associated with a higher incidence of urgent hemostatic surgery in older patients.

Although patients who underwent night-time resuscitation for out-of-hospital cardiac arrest (OHCA) had worse clinical outcomes than those who underwent day-time resuscitation, the differences between the outcomes of patients with OHCA who underwent extracorporeal cardiopulmonary resuscitation (ECPR) in the day-time and night-time remain unclear. We analyzed data from the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan. Patients were categorized according to whether they received treatment during the day-time or night-time. The primary outcomes were survival to hospital discharge and favorable neurological outcome at discharge, and the secondary outcomes were estimated low-flow time, implementation time of ECPR, and complications due to ECPR. A multivariate logistic regression model adjusted for confounders was used for comparison. Among the 1644 patients, the night-time patients had a significantly longer ECMO implementation time and estimated low-flow time than the day-time patients, along with a significantly higher number of complications than the day-time patients. However, the survival and neurologically favorable survival rates did not differ significantly between the groups. Thus, although patients who underwent ECPR at night had an increased risk of longer implementation time and complications, their clinical outcomes did not differ from those who underwent day-time ECPR.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is an option for refractory cardiac arrest, and immediate initiation after indication is recommended. However, the practical goals of ECPR preparation (such as the door-to-needle time) remain unclear. This study aimed to elucidate the association between the door-to-needle time and neurological outcomes of out-of-hospital cardiac arrest. METHODS AND RESULTS: This is a post hoc analysis of a nationwide multicenter study on out-of-hospital cardiac arrest treated with ECPR at 36 institutions between 2013 and 2018 (SAVE-J [Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan] II study). Adult patients without hypothermia (≥32 °C) in whom circulation was not returned at ECPR initiation were included. The probability of favorable neurological function at 30 days (defined as Cerebral Performance Category ≤2) was estimated using a generalized estimating equations model, in which institutional, patient, and treatment char-acteristics were adjusted. Estimated probabilities were then calculated according to the door-to-needle time with 3-minute incre-ments, and a clinical threshold was assumed. Among 1298 patients eligible for this study, 136 (10.6%) had favorable neurological function. The estimated probability of favorable outcomes was highest in patients with 1 to 3 minutes of door-to-needle time (12.9% [11.4%–14.3%]) and remained at 9% to 10% until 27 to 30 minutes. Then, the probability dropped gradually with each 3-minute delay. A 30-minute threshold was assumed, and shorter door-to-extracorporeal membrane oxygenation/low-flow time and fewer adverse events related to cannulation were observed in patients with door-to-needle time <30 minutes. CONCLUSIONS: The probability of favorable functions after out-of-hospital cardiac arrest decreased as the door-to-needle time for ECPR was prolonged, with a rapid decline after 27 to 30 minutes. REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041577; Unique identifier: UMIN000036490.

INTRODUCTION: Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%-95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS. METHODS AND ANALYSIS: ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%-95% of the target SpO2) or the control (98%-100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1-2 at 90 days after ROSC, to be compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000046914).

Background &Aims: Thiamine is an essential micronutrient for energy metabolism. Thiamine deficiency is frequently observed in critically ill patients. However, the effect of thiamine administration is unclear in critically ill patients. Methods: We conducted a systematic review and meta-analysis. To identify randomized controlled trials on the effect of thiamine administration in critically ill patients, a literature search was conducted in MEDLINE, CENTRAL, and ICHUSHI databases from inception to April 2023. Pooled effect estimates were calculated about mortality as the primary outcome and shock duration, lactate level, Sequential Organ Failure Assessment (SOFA) score, delirium, length of mechanical ventilation, length of intensive care unit (ICU) stay, infection rate, all adverse events, and Short-Form Health Survey (SF-36) as the secondary outcomes. The certainty of evidence (CoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Overall, 35 studies (3494 patients) were included. Evidence suggested that thiamine administration resulted in little to no difference in mortality (risk ratio [RR], 0.89; 95% confidence interval [CI], 0.75 to 1.06; Low CoE); however, thiamine administration may reduce shock duration (mean difference [MD], −11.43 h; 95% CI, −20.16 to −2.69 h; Low CoE), lactate level (MD, −0.34 mmol/L; 95% CI, −0.63 to −0.05 mmol/L; Low CoE), and SOFA score (MD, −1.29; 95% CI, −1.91 to −0.66; Low CoE). Conversely, thiamine administration resulted in a slight increase in the length of ICU stay (MD, 0.40 days; 95% CI, 0.01–0.79 days; High CoE). Conclusions: Although thiamine administration may reduce shock state, it may not reduce mortality, and slightly increases the length of ICU stay.