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Purpose Sex-based differences in post-traumatic mortality have been widely discussed for quite some time. We hypothesized that age-related pathophysiologic changes would affect sex-based differences in post-traumatic mortality and aimed to verify the hypothesis using a nationwide trauma registry in Japan. Methods This was a retrospective analysis of trauma patients registered in The Japanese Trauma Data Bank. We stratified the study population into the following three subsets based on age: (1) pediatric subset (age ≤ 14), (2) adult subset (age 15–50) and (3) senior adult subset (age ≥ 51). We evaluated both sex-based differences in mortality in each subset separately using multivariate logistic regression analysis and the two-way interaction effect for predicted survival between the continuous increase of age and the sexes using a nonlinear multivariate regression model. Results We included 122,819 trauma patients who fulfilled the inclusion criteria and classified them into the 3 subsets according to age. Male patients were more likely to die compared to female patients only in the senior adult subset (adjusted odds ratio: 1.26; 95% confidence interval: 1.18–1.36), whereas there were no statistically significant differences in the other two subsets. Furthermore, non-linear logistic regression analysis revealed that predicted survival probability in male patients decreased more sharply in accordance with the increase of age compared to that in female patients (p for interaction: 0.051). Conclusion Age-related change in post-traumatic mortality was significantly different between males and females, and male patients had a relatively higher risk of death in the older population.

BACKGROUND The proportion of adult patients with return of spontaneous circulation (ROSC) following out-of-hospital cardiac arrest (OHCA) remains unchanged since 2012. A better resuscitation strategy is needed. This study evaluated the effectiveness of a regional cerebral oxygen saturation (rSO2)-guided resuscitation protocol without rhythm check based on our previous study. METHODS Because defibrillation is the definitive therapy that should be performed without delay for shockable rhythm, the study subjects were OHCA patients with non-shockable rhythm on hospital arrival at three emergency departments. They were divided into three groups based on their baseline rSO2 value (%): ≥50, ≥40 to

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00068-022-02144-1., Purpose: Understanding epidemiological patterns in patients with severe sports-related injuries between children and adults is important for injury prevention. We ought to describe the characteristics and outcomes of patients with severe sports-related injuries and compare the characteristics between children and adults. Methods: We conducted a retrospective analysis of the Japan Trauma Data Bank (JTDB). We included patients with sports-related injury and an ISS of at least 16, who were admitted between 2004 and 2018. We compared characteristics between children (< 18years) and adults (≥ 18years). We performed a multivariable logistic regression analysis to compare in-hospital mortality. Results: We identified 1369 eligible patients (children, n = 326; adults, n = 1043). The most common season was April–June and July–September in children (28.5% and 27.9%) and January–March in adults (42.1%). Injuries to the head/neck (58.9% vs. 40.8%, p < 0.001) and abdomen (16.0% vs. 8.3%, p < 0.001) were significantly more frequent in children than adults, while injuries to the thorax (8.0% vs. 27.2%, p < 0.001), pelvis/lower extremity (0.6% vs. 6.0%, p < 0.001), and spine (23.9% vs. 35.3%, p < 0.001) were less frequent in children. We did not observe a statistically significant difference in in-hospital mortality between children and adults. Conclusions: We conducted a comprehensive analysis of severe sports-related injuries using a nationwide trauma database and demonstrated different patterns of severe sports-related injuries in children and adults.

Background: Large-scale data on cranial nerve injuries are scarce. Methods: This study enrolled 361,706 patients registered in the Japanese Trauma Data Bank from 2004 to 2018. We selected patients with cranial nerve injury using the corresponding Abbreviated Injury Scale codes and examined the incidence and characteristics. Results: In total, 347,101 patients were eligible for inclusion in our analysis. By mechanism of trauma, all cranial nerve injuries occurred in

Female out-of-hospital cardiac arrest (OHCA) patients have been reported to be less likely to receive cardiopulmonary resuscitation by bystanders compared with male patients in prehospital settings. However, no clinical studies have investigated gender disparities in the application of public-access automated external defibrillator (AED) pads among OHCA patients in public locations.OHCA data from 2011 to 2018 were obtained from the OHCA registry in Osaka City, Japan and OHCAs that occurred in public locations were included. Gender differences in receiving public-access AED pad application by bystanders were assessed according to the age of the OHCA patient (15, 15-49, 50-74, and ≥75 years) after controlling confounders.The analysis included 4358 OHCA patients (3313 male and 1045 female patients). The multivariable logistic regression analyses found no significant gender differences in the likelihood of public-access AED pad application among patients aged15 years (5.3% in male patients vs 6.3% in female patients; adjusted OR = 1.00, p = 1.000), 50-74 years (16.8% vs 12.7%; adjusted OR = 0.96, p = 0.796), and ≥75 years (12.3% vs 14.8%; adjusted OR = 1.45, p = 0.098). In contrast, among patients aged 15-49 years, female patients were significantly less likely to receive public-access AED pad application compared with male patients (12.1% vs 5.2%; adjusted OR = 0.54, p = 0.032).In this population, female OHCA patients of reproductive age (15-49 years) were less likely to receive public-access AED pad application compared with male patients of the same age group.

Self-harm is a common ambulance call and is potentially affected by the COVID-19 pandemic. The aim of this study was to investigate whether the incidence of ambulance transport due to self-harm increased in 2020.We undertook a population-based observational study using a database from the Osaka prefectural government. Ambulance transport of patients due to self-harm from 2016 through 2020 was investigated. We estimated adjusted incidence rate ratios using a Poisson regression model to compare the annual incidence rates of ambulance transport in 2017-2020 with those in 2016. We also provided age-stratified analysis.We analyzed 13,648 patients. There was no difference in the incidence of ambulance transport due to self-harm in 2017, 2018, 2019, and 2020 compared with 2016. In the age group of 20-29 years, despite no difference in 2017-2019 compared with 2016, we found a 13.8% increase in the incidence of ambulance transport due to self-harm in 2020 (adjusted incidence rate ratio, 1.138; 95% confidence interval, 1.025-1.265).Although there was no difference in the incidence of ambulance transport due to self-harm in 2017-2019, that in 2020 increased in the age group of 20-29 years.

Aim To assess relationships between abdominal angiography and outcomes in adults with blunt liver injuries. Methods A retrospective observational study carried out from January 2004 to December 2018. Adult blunt‐trauma patients with AAST grade Ⅲ–Ⅴ were analyzed with in‐hospital mortality as the primary outcome using propensity‐score‐(PS) matching to seek associations with abdominal angiography findings. Results A total of 1,821 patients were included, of which 854 had available abdominal angiography data (AA+) and 967 did not (AA−). From these, 562 patients were selected from each group by propensity score matching. In‐hospital mortality was found to be lower in the AA+ than in the AA− group (15.1% [87/562] versus 25.4% [143/562]; odds ratio 0.544, 95% confidence interval 0.398–0.739). Conclusion Abdominal angiography is shown to be of benefit for adult patients with blunt liver injury in terms of their lower in‐hospital mortality., Odds ratios for in‐hospital mortality related to abdominal angiography.

We comment on the study by Batra et al. on the efficacy of probiotics in the prevention of ventilator-associated pneumonia in critically ill ICU patients. They also reported that probiotics administration was not associated with a statistically significant reduction in the incidence of diarrhea (OR 0.59; CI 0.34, 1.03; P = 0.06; I2 = 38%). However, their meta-analysis missed one RCT, and when we repeated the analysis including this RCT, we found that probiotics administration significantly reduced the incidence of diarrhea (OR 0.51; CI 0.28, 0.92; P = 0.02; I2 = 45.6%). We thus believe that probiotics administration is effective in reducing the incidence of diarrhea in ventilated critically ill ICU patients.

Objectives The spread of COVID-19 has affected the incidence of other infectious diseases, but there are no reports of studies using comprehensive regional population-based data to evaluate the impact of COVID-19 on influenza incidence. We attempted to evaluate the impact of COVID-19 on influenza using the population-based ORION (Osaka Emergency Information Research Intelligent Operation Network) registry. Methods The ORION registry of emergency patients treated by emergency medical service (EMS) personnel was developed by the Osaka Prefecture government. From ORION, we included emergency patients with influenza using the ICD (International Statistical Classification of Diseases and Related Health Problems) 10 codes. Influenza incidence rate ratio (IRR) and associated 95% CI were calculated. Results The number of influenza patients transported by EMS decreased during the COVID-19 pandemic. The IRR showed a substantial decrease in influenza patients in 2020 (IRR 2020/2018 0.39, 95% CI 0.37–0.41). Conclusions A comprehensive regional analysis using the population-based ORION registry confirmed that from January 2020, when the first confirmed cases of COVID-19 infection were reported in Osaka, Japan, the number of influenza patients transported by EMS decreased dramatically.

BACKGROUND Early surveillance to prevent the spread of influenza is a major public health concern. If there is an association of influenza epidemics with mobile app data, it may be possible to forecast influenza earlier and more easily. OBJECTIVE We aimed to assess the relationship between seasonal influenza and the frequency of mobile app use among children in Osaka Prefecture, Japan. METHODS This was a retrospective observational study that was performed over a three-year period from January 2017 to December 2019. Using a linear regression model, we calculated the R2 value of the regression model to evaluate the relationship between the number of “fever” events selected in the mobile app and the number of influenza patients ≤14 years of age. We conducted three-fold cross-validation using data from two years as the training data set and the data of the remaining year as the test data set to evaluate the validity of the regression model. And we calculated Spearman correlation coefficients between the calculated number of influenza patients estimated using the regression model and the number of influenza patients, limited to the period from December to April when influenza is prevalent in Japan. RESULTS We included 29,392 mobile app users. The R2 value for the linear regression model was 0.944, and the adjusted R2 value was 0.915. The mean Spearman correlation coefficient for the three regression models was 0.804. During the influenza season (December–April), the Spearman correlation coefficient between the number of influenza patients and the calculated number estimated using the linear regression model was 0.946 (P CONCLUSIONS In this study, the number of times that mobile apps were used was positively associated with the number of influenza patients. In particular, there was a good association of the number of influenza patients with the number of “fever” events selected in the mobile app during the influenza epidemic season.

BackgroundIn the field of emergency medical care, we often experience a situation in which we cannot measure pulse oximetric saturation (SpO₂) or blood pressure due to circulatory failure associated with shock. However, as we can measure rSO₂ values of the brain even in patients with shock, we hypothesized that we could evaluate the oxygen supply-demand balance between brain and muscle tissue by simultaneously measuring regional oxygen saturation (rSO₂) values of the brain and muscle tissue of patients with shock.Case presentationWe attached a TOS-OR rSO₂ monitor (TOSTEC CO., Tokyo, Japan) to 10 healthy volunteers and measured the rSO₂ values of their brain and muscle for 3 minutes. The rSO₂ values of their brain cerebral regional oxygen saturation (crSO₂) and muscle regional oxygen saturation (mrSO₂) were 77.6±1.6% and 76.2±1.3% (mean ± SD). There was little difference between crSO₂ and mrSO₂ (cerebro-musculoskeletal difference in regional saturation of oxygen; c-mDrSO₂). However, there were discernible amount of c-mDrSO₂ in three cases with shock, Case 1 showed a prolonged shock state due to septic shock caused by bacterial pneumonia. Her crSO₂ values was always higher than her mrSO₂ value, and there was a c-mDrSO₂. Case 2 showed a decrease in mean arterial pressure (MAP) with the development of septic shock caused by intestinal perforation. His crSO₂ value was higher than that of his mrSO₂, and c-mDrSO₂ increased with the decrease of his MAP. Case 3 had a low MAP due to hemorrhagic shock caused by postpartum hemorrhage. Her crSO₂ value was higher than that of her mrSO₂ and a c-mDrSO₂ was present. After resuscitation, the c-mDrSO₂ decreased with the increase in her blood pressure.ConclusionWe evaluated the usefulness of simultaneous measurement of crSO₂ and mrSO₂ as an objective and non-invasive method in shock management. Even if SpO₂ or blood pressure could not be measured due to circulatory failure associated with shock, it was possible to measure the values of crSO₂ and mrSO₂, which changed in real time with fluctuation of the blood pressure. Unlike previous monitoring devices, the rSO₂ monitor may continuously and clearly reflect the changes in local oxygen supply-demand balance.

Hereditary angioedema has been attributed to an inherited deficiency of C1 esterase inhibitor that increases vascular permeability. The role of C1 esterase inhibitor in burn patients has not been described previously. In this study, we attempted to identify the relationship between serial changes of C1 esterase inhibitor activity and the clinical course in major burn patients. This study was a single-center, prospective, observational study. C1 esterase inhibitor activity values were serially examined in major burn patients admitted into the burn center from April 2014 to December 2016. Inclusion criteria were age ≥16 years old and %TBSA burned ≥20%. This study included 38 patients with major burn. C1 esterase inhibitor activity after burn dropped acutely on days 1 and 2 but increased immediately until days 3 to 5, after which it continued to gradually increase to above the reference value. C1 esterase inhibitor activity on admission showed significant inverse correlation with the volume of infusion per body weight required in the first 24 hours after injury and %TBSA burned (r = −0.405, P = 0.01; r = −0.375, P = 0.02, respectively). C1 esterase inhibitor activity on admission was significantly lower in the nonsurvivors than in the survivors during the 28-day evaluation period (59% vs 90%, P = 0.01). These findings suggest that C1 esterase inhibitor may play a critical role in regulating vascular permeability in the acute phase following the burn injury.

Background Cerebral oximetry (rSO2) may be useful in assessing the probability of return of spontaneous circulation (ROSC). However, the potential of assessing the trend in the rSO2 value has not been discussed when determining the probability of ROSC. Methods This was a retrospective study of out-of-hospital cardiac arrest (OHCA) patients with continuous rSO2 values recorded during cardiopulmonary arrest. We used logistic regression analysis at each time point to investigate the best subsets of rSO2-related variables for ROSC, which included rSO2 (baseline), the baseline value of rSO2; amount of maximum rise, the maximum difference of rSO2 from rSO2 (baseline) over t minutes; ΔrSO2 (t):(amount of maximum rise)/rSO2 (baseline) over t minutes after hospital arrival. Results Among the 90 included patients, 35 achieved ROSC. Area under the curve (AUC) analysis revealed that ΔrSO2 over a 16-min measurement period was significantly higher than ΔrSO2 measured over 4-, 8-, 12-, and 20-min periods. During this 16-min period, the subset showing the best AUC value was interaction of the amount of maximum rise and rSO2 (baseline) rather than the amount of maximum rise or ΔrSO2 alone (AUC = 0.91). Conclusions The combination of rSO2 (baseline) with the amount of maximum rise in rSO2 value over time might be a new index for the prediction of ROSC that could be useful in guiding cardiopulmonary resuscitation. Further studies are needed to validate these findings.

Purpose The aim of this study was to evaluate the association between the implementation of pelvic angiography (PA) and outcome in emergency pediatric patients with pelvic fracture. Methods We extracted data on pelvic fracture patients aged ≤ 19 years between 2004 and 2015 from a nationwide trauma registry in Japan. The main outcome was hospital mortality. We assessed the relationship between implementation of PA and hospital mortality using one-to-one propensity-score-matching analysis to reduce potential confounding effects in comparing the PA group with the non-PA group. Results In total, 1351 patients were eligible for our analysis, with 221 patients (16.4%) included in the PA group and 1130 patients (83.6%) included in the non-PA group. For all patients, the proportion of hospital mortality was higher in the PA group than in the non-PA group [13.6% (30/221) vs 7.1% (80/1130), crude odds ratio (OR) 2.062 (95% confidence interval (CI), 1.318–3.224); p = 0.002]. In the propensity-score-matched patients, the proportion of hospital mortality was lower in the PA group than in the non-PA group [10.5% (22/200) vs 18.2% (38/200), p = 0.027]. This finding was confirmed in both the multivariable logistic regression model [adjusted OR 0.392 (95% CI, 0.171–0.896); p = 0.026] and the conditional logistic regression model [conditional OR 0.484 (95% CI, 0.261–0.896); p = 0.021]. Conclusion The implementation of PA was significantly associated with lower hospital mortality among emergency pediatric patients with pelvic fractures compared with the non-implementation of PA.

The lack of established diagnostic criteria makes diagnosing blunt cardiac injury difficult. We investigated the factors associated with blunt cardiac injury using the Japan Trauma Data Bank (JTDB) in a multicenter observational study of blunt trauma patients conducted between 2004 and 2018. The primary outcome was the incidence of blunt cardiac/pericardial injury. Multivariable logistic regression analysis was used to identify factors independently associated with blunt cardiac injuries. Of the 228,513 patients, 1002 (0.4%) had blunt cardiac injury. Hypotension on hospital arrival (adjusted odds ratio (AOR) 4.536, 95% confidence interval (CI) 3.802–5.412), thoracic aortic injury (AOR 2.722, 95% CI 1.947–3.806), pulmonary contusion (AOR 2.532, 95% CI 2.204–2.909), rib fracture (AOR 1.362, 95% CI 1.147–1.618), sternal fracture (AOR 3.319, 95% CI 2.696–4.085). and hemothorax/pneumothorax (AOR 1.689, 95% CI 1.423–2.006)) was positively associated with blunt cardiac injury. Regarding the types of patients, car drivers had a higher rate of blunt cardiac injury compared to other types of patients. Driving a car, hypotension on hospital arrival, thoracic aortic injury, pulmonary contusion, rib fracture, sternal fracture, and hemothorax/pneumothorax were positively associated with blunt cardiac injury.

The aim of this study was to describe epidemiologic features of pediatric blunt renal trauma. We performed a retrospective analysis using the Japan Trauma Data Bank over 15 years. We included patients younger than 18 years with blunt renal trauma. We analyzed temporal trends and variations across age groups in patient characteristics, intervention, and in-hospital mortality. We also assessed factors associated with in-hospital mortality. We identified 435 pediatric patients with blunt renal trauma. Their median age was 14 years and median Injury Severity Score (ISS) was 17. The most common mechanism of injury was traffic accident in all age groups. Nephrectomy was performed in 3.2%, and the overall in-hospital mortality was 4.6%, both of which showed decreasing trends. The most common mechanism of injury by age group was a pedestrian accident in infants/toddlers/preschoolers (43.5%), pedestrian accident in middle childhood (18.5%), bicycle accident in young teens (24.7%), and motorcycle accident in teenagers (41.2%). Sports-related injury was common in young teens (23.3%) and teenagers (15.2%). Factors such as ISS, shock, concomitant injury, and nephrectomy were associated with high in-hospital mortality. We described decreasing trends in nephrectomy and in-hospital mortality in pediatric blunt renal trauma and found traffic accident and sports-related injury were common in the pediatric population in Japan.

Aim The quick Sequential Organ Failure Assessment (qSOFA) was proposed for use as a simple screening tool for sepsis. In this study, we evaluated the relationship between the prehospital use of qSOFA and prognosis in patients with sepsis or suspected sepsis using the population‐based Osaka Emergency Information Research Intelligent Operation Network (ORION) registry, which compiles prehospital ambulance data and in‐hospital information. Methods The study enrolled 437,974 patients in the ORION registry from January 1 to December 31, 2016. We selected hospitalized patients with sepsis or suspected sepsis using the appropriate codes from the International Classification of Diseases revision 10. We excluded patients with: (i) missing data (outcome, Japan Coma Scale, respiratory rate, and blood pressure); (ii) respiratory rate ≥60/min; and (iii) blood pressure ≥250 mmHg. These measures were evaluated by ambulance personnel when they first contacted the patient in the prehospital setting. The primary end‐point was discharge to death. Results In total, 12,646 patients (median age, 78 [interquartile range, 65–85] years; male, n = 6,760 [53.5%]) were eligible for our analysis. In a multivariable logistic regression analysis adjusted for confounding factors, the proportion of patients discharged to death was significantly higher for those evaluated as qSOFA positive (≥2 points) than qSOFA negative (≤1 point) (265/2,250 [11.78%] vs. 415/10,396 [3.99%]; adjusted odds ratio 2.91; 95% confidence interval, 2.47–3.43; P, In 2016, the quick Sequential Organ Failure Assessment (qSOFA) was proposed for use as a simple index for sepsis. From an analysis of the population‐based ORION registry in Osaka, Japan, our study revealed that the proportion of patients discharged to death was significantly higher in those with sepsis or suspected sepsis evaluated as qSOFA positive versus negative by emergency medical service personnel in the prehospital setting.

Introduction Cytokines compose a network and play crucial roles in the pathogenesis and prognosis of sepsis. Adipose tissue is an important immune endocrine organ that releases adipocytokines. This study aimed to evaluate adipocytokines in sepsis from a network perspective. Materials and methods This retrospective study of 37 patients with sepsis and 12 healthy controls was conducted from February 2014 to July 2015. Blood samples were collected from patients on days 1 (within 24 h of diagnosis), 2, 4, 6, 8, 11, and 15 and from healthy controls. Adipocytokines (adiponectin, leptin, resistin, chemerin, visfatin, vaspin, CXCL-12/SDF-1, angiotensinogen), inflammatory cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α, monocyte chemotactic protein [MCP-1]), and plasminogen activator inhibitor-1 were measured. Acute Physiology and Chronic Health Evaluation II score was evaluated on day 1, and Sequential Organ Failure Assessment (SOFA) score and Japanese Association for Acute Medicine (JAAM) and International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation (DIC) scores were assessed at the times of blood sampling. Results Hierarchical clustering analysis showed the cluster formed by resistin, IL-6, IL-8, MCP-1, and IL-10 on days 1, 2, and 4 represented the cytokine network throughout the acute phase of sepsis. Each cytokine in this network was significantly associated with SOFA and JAAM DIC scores over the acute phase. A Cox proportional hazards model focusing on the acute phase showed a significant relation of these five cytokines with patient prognosis. Conclusions Adipocytokines and an inflammatory cytokine profile assessed over time in sepsis patients showed that resistin was involved in an inflammatory cytokine network including IL-6, IL-8, IL-10, and MCP-1 in the acute phase of sepsis, and this network was associated with severity and prognosis of sepsis.

BACKGROUND When children suffer sudden illness or injury, many parents wonder whether they should go to the hospital immediately or call an ambulance. In 2015, we developed a mobile app that allows parents or guardians to determine the urgency of their child’s condition or call an ambulance and that indicates available hospitals and clinics when their child is suddenly sick or injured by simple selection of the child’s chief complaints and symptoms. However, the effectiveness of medical apps used by the general public has not been well evaluated. OBJECTIVE The purpose of this study was to clarify the use profile of this mobile app based on data usage in the app. METHODS This study was a descriptive epidemiological study with a 4-year study period running from January 2016 to December 2019. We included cases in which the app was used either by the children themselves or by their parents and other guardians. Cases in which the app was downloaded but never actually used were excluded from this study. Continuous variables are presented as median and IQR, and categorical variables are presented as actual number and percentages. RESULTS The app was used during the study period for 59,375 children whose median age was 1 year (IQR 0-3 years). The app was used for 33,874 (57.05%) infants, 16,228 (27.33%) toddlers, 8102 (13.65%) elementary school students, and 1117 (1.88%) junior high school students, with 54 (0.09%) having an unknown status. Furthermore, 31,519 (53.08%) were male and 27,329 (46.03%) were female, with sex being unknown for 527 (0.89%) children. “Sickness” was chosen for 49,101 (78.51%) patients, and “injury, poisoning, foreign, substances and others” was chosen for 13,441 (21.49%). For “sickness,” “fever” was the most commonly selected option (22,773, 36.41%), followed by “cough” (4054, 6.48%), and “nausea/vomiting” (3528, 5.64%), whereas for “injury, poisoning, foreign substances and others,” “head and neck injury” was the most commonly selected option (3887, 6.22%), followed by “face and extremities injury” (1493, 2.39%) and “injury and foreign substances in eyes” (1255, 2.01%). CONCLUSIONS This study clarified the profile of use of a self-triage app for pediatric emergency patients in Japan.

Aim Self‐inflicted injury, as one reason to visit the emergency department, is an important issue in emergency medicine around the world. However, the impact of changes in social systems, such as medical reimbursement revision, on ambulance transport for self‐inflicted injury remains unclear. The aim of this study was to assess the impact of medical reimbursement revision on the emergency transport of self‐inflicted injury patients using nationwide ambulance records. Methods This was a retrospective observational study from April 2012 to March 2016. We analyzed nationwide ambulance records in Japan, and included self‐inflicted injury, drug poisoning, and drug overdose patients transported to hospitals by ambulance. The primary outcome of this study was age‐adjusted number of self‐inflicted injury patients transported by ambulance in each month per 1 million standard populations. To assess the impact of the medical reimbursement revision in 2014, we calculated the R 2, regression coefficients and 95% confidence interval (CI) using interrupted time series analysis. Results This study included 148,873 patients. The R 2 for the interrupted time series model was 0.821. The regression coefficient for the time trend before the medical reimbursement revision was 0.167 (95% CI, 0.090 to 0.244; p, This retrospective observational study assessed the impact of medical reimbursement revision about emergency transport of self‐inflicted injury by ambulance and restriction of prescriptions of multiple psychiatric drugs with interrupted time series analysis. In this study, we revealed that this medical reimbursement revision helped to decrease the number of patients with self‐inflicted injury transported to hospitals by ambulance.

Background: The cytokines compose a network and play a crucial role in the pathogenesis and prognosis of sepsis. Adipose tissue is noted as an important immune endocrine organ that releases adipocytokines. The aim of this study was to evaluate the adipocytokines in sepsis from a network perspective.Methods: This retrospective study comprising 37 patients with sepsis and 12 healthy controls was conducted from February 2014 to July 2015. Blood samples (maximum of 7 samples per patient, 185 samples in total) were collected from the patients on days 1 (within 24 hours of the diagnosis), 2, 4, 6, 8, 11 and 15 and from the healthy controls. Adipocytokines (adiponectin, leptin, resistin, chemerin, visfatin, vaspin, CXCL-12/SDF-1, angiotensinogen), inflammatory cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α, MCP-1), and PAI-1 were measured. The APACHE II score was evaluated on day 1, and the SOFA score and JAAM and ISTH overt disseminated intravascular coagulation (DIC) scores were assessed at the same time points at which blood was sampled.Results: Hierarchical clustering analysis showed that the cluster formed by resistin, IL-6, IL-8, MCP-1, and IL-10 on days 1, 2 and 4 represented the cytokine network throughout the acute phase of sepsis. There was a significant association of each cytokine in this network with SOFA and JAAM DIC scores over the acute phase. In a Cox proportional hazards model focusing on the acute phase, each of these cytokines showed a significant relation with patient prognosis.Conclusions: Adipocytokines and an inflammatory cytokine profile were assessed over time in patients with sepsis. We found that resistin was involved in an inflammatory cytokine network including IL-6, IL-8, IL-10 and MCP-1 in the acute phase of sepsis, and this network was associated with the severity and prognosis of sepsis.

In this study, we merged the telephone triage data set with the ORION data set and revealed the profile and outcome of patients transported by ambulance after telephone triage. Most of the patients who were transported by ambulance after telephone triage returned home after visiting the emergency department, and cerebral infarction was the most common diagnosis among the patients who were hospitalized., Aim Details such as diagnosis and outcome of patients transported by ambulance after telephone triage have not been fully revealed. The aim of this study was to reveal profile and outcome about patients transported by ambulance via telephone triage with dataset of telephone triage and population‐based registry for emergency patients. Methods This retrospective descriptive study with a one‐year study period from January 1, 2016 to December 31, 2016 included patients selected from the telephone triage dataset who were transported by ambulance. Key parameters such as age, sex and date and time of ambulance dispatch were used to identify patient data from the ORION registry. We assessed the profile and outcome of the patients in a descriptive epidemiological analysis. Results We included 4,293 patients in the selected datasets whose data were merged, of whom 2,998 patients (69.8%) returned home from the emergency department, 1,255 (29.2%) were hospitalized, 32 (0.7%) were transferred to other hospitals, and 8 (0.2%) died. The most common diagnosis in the emergency departments was “infectious gastroenteritis and colitis, unspecified [A09] (219, 5.1%)”. Among the 1,255 hospitalized patients, 905 patients (72.1%) were discharged home, 254 patients (20.2%) remained hospitalized, 52 patients (4.1%) were transferred to other hospitals, 38 patients (3.0%) died, and 5 patients (0.5%) had missing data. The most common diagnosis was “cerebral infarction [I63.0‐I63.9] (138, 11.0%)”. Conclusion This study revealed the profile and outcome of patients transported by ambulance after telephone triage.

Purpose The aim of this study was to assess the effect of fluid administration by emergency life-saving technicians (ELST) on the prognosis of traffic accident patients by using a propensity score (PS)-matching method. Methods The study included traffic accident patients registered in the JTDB database from January 2016 to December 2017. The main outcome was hospital mortality, and the secondary outcome was cardiopulmonary arrest on hospital arrival (CPAOA). To reduce potential confounding effects in the comparisons between two groups, we estimated a propensity score (PS) by fitting a logistic regression model that was adjusted for 17 variables before the implementation of fluid administration by ELST at the scene. Results During the study period, 10,908 traffic accident patients were registered in the JTDB database, and we included 3502 patients in this study. Of these patients, 142 were administered fluid by ELST and 3360 were not administered fluid by ELST. After PS matching, 141 patients were selected from each group. In the PS-matched model, fluid administration by ELST at the scene was not associated with discharge to death (crude OR: 0.859 [95% CI, 0.500–1.475]; p = 0.582). However, the fluid group showed statistically better outcome for CPAOA than the no fluid group in the multiple logistic regression model (adjusted OR: 0.231 [95% CI, 0.055–0.967]; p = 0.045). Conclusion In this study, fluid administration to traffic accident patients by ELST was associated not with hospital mortality but with a lower proportion of CPAOA.

BackgroundIn 2016, the quick Sequential Organ Failure Assessment (qSOFA) was proposed for use as a simple screening tool for sepsis, with sepsis suspected at a score ≥ 2 points. In this study, we evaluated the effectiveness of prehospital qSOFA for predicting prognosis in patients with sepsis or suspected sepsis using the population-based Osaka Emergency Information Research Intelligent Operation Network (ORION) registry, which compiles prehospital ambulance data and in-hospital information.MethodsThe study enrolled 437,974 patients in the ORION registry from January 1 to December 31, 2016. We selected hospitalized patients with sepsis or suspected sepsis using the appropriate ICD 10 codes. We excluded the patients with i) missing data (outcome, Japan Coma Scale, respiratory rate, blood pressure), ii) respiratory rate ≥ 60/min, and iii) blood pressure ≥ 250 mmHg. These measures were evaluated by ambulance personnel when they first contacted the patient in the prehospital setting. The primary endpoint was discharge to death.ResultsIn total, 12,646 patients (median age: 78 [IQR: 65–85] years, male: n = 6760 [53.5%]) were eligible for our analysis. In a multivariable logistic regression analysis adjusted for confounding factors, the proportion of patients discharge to death was significantly higher for qSOFA positive (≥ 2 points) than negative (≤ 1 point) (265/2250 [11.78%] vs. 415/10,396 [3.99%]; adjusted odds ratio 2.909; 95% confidence interval 2.469–3.428, p

Background Early surveillance to prevent the spread of influenza is a major public health concern. If there is an association of influenza epidemics with mobile app data, it may be possible to forecast influenza earlier and more easily. Objective We aimed to assess the relationship between seasonal influenza and the frequency of mobile app use among children in Osaka Prefecture, Japan. Methods This was a retrospective observational study that was performed over a three-year period from January 2017 to December 2019. Using a linear regression model, we calculated the R2 value of the regression model to evaluate the relationship between the number of “fever” events selected in the mobile app and the number of influenza patients ≤14 years of age. We conducted three-fold cross-validation using data from two years as the training data set and the data of the remaining year as the test data set to evaluate the validity of the regression model. And we calculated Spearman correlation coefficients between the calculated number of influenza patients estimated using the regression model and the number of influenza patients, limited to the period from December to April when influenza is prevalent in Japan. Results We included 29,392 mobile app users. The R2 value for the linear regression model was 0.944, and the adjusted R2 value was 0.915. The mean Spearman correlation coefficient for the three regression models was 0.804. During the influenza season (December–April), the Spearman correlation coefficient between the number of influenza patients and the calculated number estimated using the linear regression model was 0.946 (P Conclusions In this study, the number of times that mobile apps were used was positively associated with the number of influenza patients. In particular, there was a good association of the number of influenza patients with the number of “fever” events selected in the mobile app during the influenza epidemic season.

Background The hemoglobin index (HbI) represents the amount of hemoglobin, which reflects the regional tissue blood volume. The HbI is calculated by a regional oxygen saturation monitor. In freshwater drowning, inhaled water is immediately absorbed into the blood causing hemodilution. We hypothesized that this blood dilution could be observed in real time using HbI values in patients with out-of-hospital cardiac arrest (OHCA) due to freshwater drowning. Methods In this single-center retrospective, observational study, we examined the HbI in patients with OHCA due to freshwater drowning from April 2015 to May 2020. Patients with OHCA due to hanging were selected as a control group. Results Thirty-two patients in the freshwater drowning group and 21 in the control group were eligible for inclusion. In the freshwater drowning group, the HbI values in the return of spontaneous circulation (ROSC) group were significantly decreased in comparison to the non-ROSC group (-0.28 [IQR -0.55, -0.12] vs. -0.04 [IQR -0.16, 0.025]; p = 0.024). In the control group, the change of HbI during resuscitation in the ROSC and non-ROSC groups was not significantly different (0.11 [IQR -0.3525, 0.4225] vs. -0.02 [IQR -0.14, 0.605]; p = 0.8228). In each patient with ROSC in the freshwater drowning group, the HbI value after ROSC was significantly decreased in comparison to before ROSC (1.2±0.5 vs. 0.9±0.5]; p = 0.0156). In contrast, this difference was not observed in patients with an ROSC in the control group (3.7±1.3 vs. 3.8±1.4]; p = 0.7940). Conclusion Blood dilution induced by freshwater drowning might be detected in real time using the HbI. To prove the validity of this research's result, further prospective large study is needed.

Background: Regional cerebral oxygen saturation (rSO2) is a non-invasive method of measuring cerebral perfusion; However, serial changes in cerebral rSO2 values among out-of-hospital cardiac arrest (OHCA) patients in pre-hospital settings have not been sufficiently investigated. We aimed to investigate the association between the serial change in rSO2 pattern and patient outcome. Methods: We evaluated rSO2 in OHCA patients using portable monitoring by emergency life-saving technicians (ELTs) from June 2013 to December 2019 in Osaka City, Japan. We divided the patterns of serial of rSO2 change into type 1 (increasing pattern) and type 2 (non-increasing pattern). Patients in whom measurement started after return of spontaneous circulation (ROSC) were excluded. The outcome measures were ‘Prehospital ROSC’, ‘Alive at admission’, ‘1-month survival’ and ‘Cerebral Performance Category (CPC) 1 or 2′. Results: Eighty-seven patients were eligible for this analysis (type 1: n = 40, median age: 80.5 [IQR: 72–85.5] years, male: n = 20 [50.0%]; type 2: n = 47, 81 [72–85.5] years, male: n = 28 [59.6%]). In a multivariable logistic regression adjusted for confounding factors, outcomes of ‘Prehospital ROSC’ and ‘Alive at admission’ were significantly higher in type 1 than type 2 pattern (11/40 [27.5%] vs. 2/47 [4.26%], AOR 5.67, 95% CI 1.04–30.96, p

Resuscitative endovascular balloon occlusion of the aorta (REBOA) performed by emergency physicians has been gaining acceptance as a less invasive technique than resuscitative thoracotomy.To evaluate access-related complications and duration of occlusions during REBOA.Patients with haemorrhagic shock requiring REBOA, from 18 hospitals in Japan, included in the DIRECT-IABO Registry were studied. REBOA-related characteristics were compared between non-survivors and survivors at 24 hours. 24-Hour survivors were categorised into groups with small (≤8 Fr), large (≥9 Fr) or unusual sheaths (oversized or multiple) to assess the relationship between the sheath size and complications. Haemodynamic response, occlusion duration and outcomes were compared between groups with partial and complete REBOA.Between August 2011 and December 2015, 142 adults undergoing REBOA were analysed. REBOA procedures were predominantly (94%) performed by emergency medicine (EM) physicians. The median duration of the small sheath (n=53) was 19 hours compared with 7.5 hours for the larger sheaths (P=0.025). Smaller sheaths were more likely to be removed using external manual compression (96% vs 45%, P0.001). One case of a common femoral artery thrombus (large group) and two cases of amputation (unusual group) were identified. Partial REBOA was carried out in more cases (n=78) and resulted in a better haemodynamic response than complete REBOA (improvement in haemodynamics, 92% vs 70%, P=0.004; achievement of stability, 78% vs 51%, P=0.007) and allowed longer occlusion duration (median 58 vs 33 min, P=0.041). No statistically significant difference in 24-hour or 30-day survival was found between partial and complete REBOA.In Japan, EM physicians undertake the majority of REBOA procedures. Smaller sheaths appear to have fewer complications despite relatively prolonged placement and require external compression on removal. Although REBOA is a rarely performed procedure, partial REBOA, which may extend the occlusion duration without a reduction in survival, is used more commonly in Japan.

Aim The aim of our study is to describe the characteristics of patients who use emergency medical services (EMS), EMS performance, and regional variations in Japan. Methods We undertook a nationwide, population‐based, descriptive review of anonymized ambulance transport records obtained from the Fire and Disaster Management Agency in Japan. All emergency patients transported to emergency medical institutions by EMS personnel from January to December 2016 were enrolled in this study, excluding patients who were not transported. Results During the study period, 5,097,838 patients were transported to a hospital. Their median age was 69 years, 51.4% were male, and 56.5% were over 65 years old. Median durations from EMS call to EMS arrival on scene were similar among the regions, ranging from 7 to 9 min. However, the longest median duration from EMS call to hospital arrival was 38 min, and the shortest was 31 min across the regions. Among all patients, 350,865 (6.9%) were assessed as being in a severe condition, 14,410 (0.3%) were in very severe condition, and 74,780 (1.5%) were confirmed to be dead at the time of initial medical examination in the emergency department. Conclusions We described the characteristics of emergency patients and EMS performance in Japan. This registry serves as a basis for providing relevant information to improve prehospital emergency medical systems., This observational study describes the characteristics of emergency patients and emergency medical services (EMS) performance in Japan in 2016. We report the results from 5,097,838 patients transported to an emergency medical institution by EMS personnel. We assessed comprehensive data on the characteristics of the emergency patients, EMS performance, and underlying regional variations.

Background: Replacing traditional surveillance with syndromic surveillance is one of the major interests in public health. However, it is unclear whether the number of influenza patients is associated with the number of telephone triages in Japan. Methods: This retrospective, observational study was conducted over the six-year period between January 2012 to December 2017. We used the dataset of a telephone triage service in Osaka, Japan and the data on influenza patients published from the Information Center of Infectious Disease in Osaka prefecture. Using a linear regression model, we calculated Spearman’s rank-order coefficient and R 2 of the regression model to assess the relationship between the number of telephone triages for fever and the number of influenza patients in Osaka. Furthermore, we calculated Spearman’s rank-order coefficient and R 2 between the predicted weekly number of influenza patients from the linear regression model and the actual weekly number of influenza patients for each season (January-March, April-June, July-September, October-December). Results: There were 465,971 patients with influenza, and the number of telephone triages for fever was 420,928 among 1,065,628 total telephone triages during the study period. Our analysis showed that the Spearman rank-order coefficient was 0.932 and R 2 and adjusted R 2 were 0.869 and 0.842, respectively. The highest Spearman rank-order coefficient was 0.896 ( P

Aim The hemoglobin index (HbI) represents the amount of hemoglobin, which reflects regional tissue blood volume. The HbI is calculated in real time by a regional oxygen saturation (rSO 2) monitor. For the hypothesis of our HbI project, we theorized that HbI could be a new method for the screening of subarachnoid hemorrhage (SAH) in overcrowded emergency departments. As a first step, this study aimed to clarify the effectiveness of HbI in screening SAH in out‐of‐hospital cardiopulmonary arrest (OHCA) patients using the rSO 2 data of our previous studies. Methods In this single‐center, retrospective, observational study, we examined HbI in patients with OHCA transferred to the Trauma and Acute Critical Care Center at Osaka University Hospital (Osaka, Japan) during the period between April 2013 and December 2015. A sensor attached to the patient's forehead monitored HbI continuously. Results Among 63 patients (40 men and 23 women; mean age, 76 [interquartile range (IQR), 66–85] years) with OHCA, five were diagnosed as having SAH (SAH group) and 58 were not (non‐SAH group). The HbI values were significantly higher in the SAH group than in the non‐SAH group (1.35 [IQR: 0.80–2.69] versus 0.41 [IQR: 0.32–0.61]), P = 0.0042). In the SAH group, with an HbI cut‐off value of 1.18, the specificity and sensitivity were 96% and 80%, respectively, and the area under the receiver operating characteristic curve of HbI was 0.89. Conclusions The HbI might be useful for the screening of SAH in patients with OHCA. The application of HbI in the emergency department could be expected in the future., The regional oxygen saturation monitor calculates regional tissue blood volume based on the hemoglobin index (HbI), which indicates the amount of hemoglobin present. We show that the values of HbI were significantly higher in the subarachnoid hemorrhage (SAH) group than in the non‐SAH group and that the area under the receiver operating characteristic curve showed high accuracy for the diagnosis of SAH. Our analysis suggests that HbI might be useful for the screening of SAH in OHCA patients.

Katayama Y, Kitamura T, Kiyohara K, et al. Prehospital factors associated with death on hospital arrival after traffic crash in Japan: a national observational study. BMJ Open 2019;9:e025350. doi: 10.1136/bmjopen-2018-025350, Objective Although it is important to assess prehospital factors associated with traffic crash fatalities to decrease them as a matter of public health, such factors have not been fully revealed. Methods Using data from the Japanese Trauma Data Bank, a large hospital-based trauma registry in Japan, we retrospectively analysed traffic crash patients transported to participating facilities that treated patients with severe trauma from 2004 to 2015. This study defined registered emergency patients whose systolic blood pressure was 0 mm Hg or heart rate was 0 bpm at hospital arrival as being in prehospital cardiopulmonary arrest (CPA). Prehospital factors associated with prehospital CPA due to traffic crash were assessed with multivariable logistic regression analysis. Results In total, 66 243 patients were eligible for analysis. Of them, 3390 (5.1%) patients were in CPA at hospital arrival. A multivariable logistic regression model showed the following factors to be significantly associated with prehospital CPA: ages 60-74 years (adjusted OR (AOR) 1.256, 95% CI 1.142 to 1.382) and ≥75 years (AOR 1.487, 95% CI 1.336 to 1.654), male sex (AOR 1.234, 95% CI 1.139 to 1.338), night-time (AOR 1.575, 95% CI 1.458 to 1.702), weekend including holiday (AOR 1.078, 95% CI 1.001 to 1.161), rural area (AOR 1.181, 95% CI 1.097 to 1.271), back seat passenger (AOR 1.227, 95% CI 0.985 to 1.528) and pedestrian (AOR 1.754, 95% CI 1.580 to 1.947) as types of patients. Conclusion In this population, factors associated with prehospital CPA due to a traffic crash were elderly people, male sex, night-time, weekend/holiday, back seat passenger, pedestrian and rural area. These fundamental data may be of help in reducing and preventing traffic crash deaths.

Objective C1 inhibitor (C1INH) regulates not only the complement system but also the plasma kallikrein-kinin, fibrinolytic, and coagulation systems. The biologic activities of C1INH can be divided into the regulation of vascular permeability and anti-inflammatory functions. The objective was to clarify the serial change of C1INH in patients with sepsis. Methods We serially examined C1INH activity values (reference range, 70%-130%) and quantitative values (reference range, 160-330 μ g/mL) in patients with sepsis admitted into the intensive care unit of the Trauma and Acute Critical Care Center at Osaka University Hospital (Osaka, Japan) during the period between December 2012 and February 2013. We also analyzed their clinical course. We defined "refractory shock" as septic shock requiring steroid administration to maintain hemodynamics. Results The serial change of C1INH was evaluated in 5 patients (4 survivors and 1 nonsurvivor). Two patients were diagnosed as having refractory shock. In the nonsurvivor after refractory shock, C1INH activity on admission was 97.2%, and the quantitative value was 133.1 μ g/mL. In the other patient with refractory shock, C1INH activity on admission was 94.4%, and the quantitative value was 126.7 μ g/mL. This patient's general condition had improved by day 6, with increases in C1INH activity (139.9%) and quantitative value (250.1 μ g/mL). In the 3 nonrefractory shock patients, C1INH activity on admission was 130.6%±8.7%, and the quantitative value was 215±26.5 μ g/mL. Conclusions Enhancement of C1INH activity was not observed in the refractory shock patients, and the C1INH quantitative values were low. Further evaluation of the serial change of C1INH and the validity of C1INH replacement therapy in patients with septic shock may lead to a new strategy for sepsis management.

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, which is the most common neoplastic disease of cattle and is closely related to human T-cell leukemia viruses. We investigated the role of a new host protein, PRMT5, in BLV infection. We found that PRMT5 is overexpressed only in BLV-infected cattle with a high proviral load, but not in those with a low proviral load. Furthermore, this upregulation continued to the lymphoma stage. PRMT5 expression was upregulated in response to experimental BLV infection, moreover, PRMT5 upregulation began in an early stage of BLV infection rather than after a long period of proviral latency. Second, siRNA-mediated PRMT5 knockdown enhanced BLV gene expression at the transcript and protein levels. Additionally, a selective small-molecule inhibitor of PRMT5 (CMP5) enhanced BLV gene expression. Interestingly, CMP5 treatment, but not siRNA knockdown, altered the gp51 glycosylation pattern and increased the molecular weight of gp51, thereby decreasing BLV-induced syncytium formation. This was supported by the observation that CMP5 treatment enhanced the formation of the complex type of N-glycan more than the high mannose type. In conclusion, PRMT5 overexpression is related to the development of BLV infection with a high proviral load and lymphoma stage and PRMT5 inhibition enhances BLV gene expression. This is the first study to investigate the role of PRMT5 in BLV infection in vivo and in vitro and to reveal a novel function for a small-molecule compound in BLV-gp51 glycosylation processing.

Supplemental Digital Content is available in the text, Motor vehicle accidents (MVAs) are one of the major public health burdens worldwide. In particular, MVAs by elderly drivers have been significantly increasing in recent years in industrialized countries. This study aimed to assess the MVA characteristics and outcomes caused by elderly drivers in Japan. Japan Trauma Data Bank (JTDB) is a prospective, nationwide, hospital-based registry for trauma patients from 256 institutions in Japan. This study enrolled all MVA drivers older than the legal age for driving between 2004 and 2015. The included patients were divided into the following 3 groups: adults (aged ≤64 years), young-old (aged 65–74 years), and old-old (aged ≥75 years). The primary outcome was in-hospital mortality. The trend in the proportion of MVAs caused by the young-old or the old-old group was evaluated using the Cochran–Armitage trend test. To assess the association of the old-old group with in-hospital mortality, compared with the adult group, we used multivariable logistic regression analysis. During the study period, a total of 236,698 trauma patients were registered, and 39,691 patients (16.8%) were eligible for our analysis. The proportion of MVAs caused by elderly drivers aged ≥65 years significantly increased from 11.7% in 2004 to 23.8% in 2015 (P

Sepsis remains a major cause of death. Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focussed on the associations of a cytokine network with prognosis and disease severities in sepsis. This retrospective study included 31 patients with sepsis and 13 healthy controls. Blood samples were collected from patients on days 1, 2, 4, 6, 8, 11 and 15 and from healthy controls. Levels of PAI-1, IFN-α, IFN-γ, IL-1β, IL-6, IL-8, IL-12/IL-23p40, IL-17A, TNF-α, MCP-1, IL-4 and IL-10 were measured. SOFA, JAAM DIC and ISTH DIC scores were evaluated at the same times blood samples were taken. Network analysis revealed a network formed by PAI-1, IL-6, IL-8, MCP-1 and IL-10 on days 1, 2 and 4 throughout the acute phase of sepsis. There were positive correlations of each cytokine and the combined score (IL-6 + IL-8 + IL-10 + MCP-1) with the SOFA, JAAM DIC and ISTH DIC scores throughout the acute phase. A Cox proportional hazards model focussed on the acute phase showed that the above combined score was significantly related with patient prognosis, suggesting that the cytokine network of IL-6, IL-8, MCP-1 and IL-10 could play a pivotal role in the acute phase of sepsis.

Cerebral oximetry (rSOThis was a retrospective study of out-of-hospital cardiac arrest (OHCA) patients with continuous rSOAmong the 90 included patients, 35 achieved ROSC. Area under the curve (AUC) analysis revealed that ΔrSOThe combination of rSO

Background C1 inhibitor (C1-INH), which belongs to the superfamily of serine protease inhibitors, regulates the complement system and also the plasma kallikrein-kinin, fibrinolytic, and coagulation systems. The biologic activities of C1-INH can be divided into the regulation of vascular permeability and anti-inflammatory functions. The objective of this study was to clarify the serial change of C1-INH in patients with sepsis and evaluate the relationship with the shock severity. Methods This was a single-center, prospective, observational study. We serially examined C1-INH activity values (normal range 70–130%) in patients with sepsis admitted into the intensive care unit of the Trauma and Acute Critical Care Center at Osaka University Hospital (Osaka, Japan) during the period between January 2014 and August 2015. We defined “refractory shock” as septic shock unresponsive to conventional therapy such as adequate fluid resuscitation and vasopressor therapy to maintain hemodynamics. Results Serial changes of C1-INH were evaluated in 40 patients with sepsis (30 men, 10 women; 30 survivors, 10 non-survivors; mean age, 70 ± 13.5 years). We divided the patients into three groups: non-shock group (n = 14), non-refractory shock group (n = 13), and refractory shock group (n = 13: 3 survivors, 10 non-survivors). In the non-shock group, C1-INH was 107.3 ± 26.5% on admission and 104.2 ± 22.3% on day 1, and it increased thereafter to 128.1 ± 26.4% on day 3, 138.3 ± 21.2% on day 7, and 140.3 ± 12.5% on day 14 (p