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BackgroundHereditary angioedema (HAE), a rare genetic disease, induces acute attacks of swelling in various regions of the body. Its prevalence is estimated to be 1 in 50,000 people, with no reported bias among different ethnic groups. However, considering the estimated prevalence, the number of patients in Japan diagnosed with HAE remains approximately 1 in 250,000, which means that only 20% of potential HAE cases are identified. ObjectiveThis study aimed to develop an artificial intelligence (AI) model that can detect patients with suspected HAE using medical history data (medical claims, prescriptions, and electronic medical records [EMRs]) in the United States. We also aimed to validate the detection performance of the model for HAE cases using the Japanese dataset. MethodsThe HAE patient and control groups were identified using the US claims and EMR datasets. We analyzed the characteristics of the diagnostic history of patients with HAE and developed an AI model to predict the probability of HAE based on a generalized linear model and bootstrap method. The model was then applied to the EMR data of the Kyoto University Hospital to verify its applicability to the Japanese dataset. ResultsPrecision and sensitivity were measured to validate the model performance. Using the comprehensive US dataset, the precision score was 2% in the initial model development step. Our model can screen out suspected patients, where 1 in 50 of these patients have HAE. In addition, in the validation step with Japanese EMR data, the precision score was 23.6%, which exceeded our expectations. We achieved a sensitivity score of 61.5% for the US dataset and 37.6% for the validation exercise using data from a single Japanese hospital. Overall, our model could predict patients with typical HAE symptoms. ConclusionsThis study indicates that our AI model can detect HAE in patients with typical symptoms and is effective in Japanese data. However, further prospective clinical studies are required to investigate whether this model can be used to diagnose HAE.

ABSTRACT: Bovine leukemia virus (BLV) has spread worldwide and causes serious problems in the cattle industry owing to the lack of effective treatments and vaccines. Bovine leukemia virus is transmitted via horizontal and vertical infection, and cattle with high BLV proviral load (PVL), which is a useful index for estimating disease progression and transmission risk, are considered major infectious sources within herds. The PVL strongly correlates with highly polymorphic bovine lymphocyte antigen (BoLA)-DRB3 alleles. The BoLA-DRB3*015:01 and *012:01 alleles are known susceptibility-associated markers related to high PVL, and cattle with susceptible alleles may be at a high risk of BLV transmission via direct contact with healthy cows. In contrast, the BoLA-DRB3*009:02 and *014:01:01 alleles comprise resistant markers associated with the development of low PVL, and cattle with resistant alleles may be low-risk spreaders for BLV transmission and disrupt the BLV transmission chain. However, whether polymorphisms in BoLA-DRB3 are useful for BLV eradication in farms remains unknown. Here, we conducted a validation trial of the integrated BLV eradication strategy to prevent new infection by resistant cattle and actively eliminate susceptible cattle in addition to conventional BLV eradication strategies to maximally reduce the BLV prevalence and PVL using a total of 342 cattle at 4 stall-barn farms in Japan from 2017 to 2019. First, we placed the resistant milking cattle between the BLV-positive and BLV-negative milking cattle in a stall barn for 3 yr. Interestingly, the resistant cattle proved to be an effective biological barrier to successfully block the new BLV infections in the stall-barn system among all 4 farms. Concomitantly, we actively eliminated cattle with high PVL, especially susceptible cattle. Indeed, 39 of the 60 susceptible cattle (65%), 76 of the 140 neutral cattle (54%), and 20 of the 41 resistant cattle (48.8%) were culled on 4 farms for 3 years. Consequently, BLV prevalence and mean PVL decreased in all 4 farms. In particular, one farm achieved BLV-free status in May 2020. By decreasing the number of BLV-positive animals, the revenue-enhancing effect was estimated to be ¥5,839,262 ($39,292.39) for the 4 farms over 3 yr. Our results suggest that an integrated BLV eradication program utilization of resistant cattle as a biological barrier and the preferential elimination of susceptible cattle are useful for BLV infection control.

BackgroundIn many countries, emergency medical systems were responsible for initial treatment of patients with COVID-19. Generally, acceptance by medical institutions may not be sufficient, and it may take much time to determine the medical institution to which to transport the patient. This problem is termed “difficulty in hospital acceptance (DIH),” and it is used as a key performance indicator in the assessment of the EMS in Japan. The purpose of this study was to reveal the factors associated with the DIH during the COVID-19 pandemic using dataset in the ORION (Osaka emergency information Research Intelligent Operation Network system).MethodsThis was a retrospective descriptive study with a 3-year study period from January 1, 2019 to December 31, 2021. We included patients who were recorded in the ORION system during the study period. The primary endpoint was defined as DIH. Multivariable logistic regression model was used to assess factors associated with DIH during the COVID-19 pandemic and calculated their adjusted odds ratio (AOR) and associated 95% confidence interval (CI).Results1,078,850 patients included in this study. Of them, 41,140 patients (3.8%) experienced DIH and 1,037,710 patients (96.2%) did not experience DIH. The median age was 71 years (IQR: 45–82), and 543,760 patients (50.4%) were male. In this study, SpO2, body temperature, and epidemic period of COVID-19 were associated with difficulty in hospital acceptance. The highest AOR of SpO2 was 80% or less (AOR: 1.636, [95% CI: 1.532–1.748]), followed by 81–85% (AOR: 1.584, [95% CI: 1.459–1.721]). The highest AOR of body temperature was 38.0–38.9°C (AOR: 1.969 [95% CI: 1.897–2.043]), followed by 39°C or higher (AOR: 1.912 [95% CI: 1.829–1.998]). The highest AOR of epidemic period of COVID-19 was the 4th wave (AOR: 2.134, [95% CI: 2.065–2.205]), followed by the 3rd wave (AOR: 1.842, [95% CI: 1.785–1.901]).ConclusionIn this study, we revealed factors associated with the DIH during the COVID-19 pandemic. As various factors are involved in the spread of an unknown infectious disease, it is necessary not only to plan in advance but also to take appropriate measures according to the situation in order to smoothly accept emergency patients.

Abstract Introduction Methemoglobinemia is a condition in which methemoglobin is increased and the oxygen carrying capacity of tissues is decreased, causing a lack of oxygen to the whole body. RNA (ribonucleic acid) sequencing technologies have made it possible to systematically examine how the human transcriptome responds to invasive pathologies. To our knowledge, no previous studies have reported the results of RNA sequencing in a patient with methemoglobinemia. We describe the analysis of RNAs from the whole blood of a patient with methemoglobinemia. Case presentation A 31-year-old Japanese man was brought to our hospital with symptoms of dyspnea due to inhalation of gas from an acetic acid phosphonitrate storage tank at a factory. The nitrogen oxide concentration measured around the storage tank was over 2500 ppm, and he witnessed orange–brown smoke at that time. After entering the area and taking a few breaths, he suddenly became unwell, with dyspnea and numbness in his extremities. He was evacuated from the area within a few minutes, at which time he was suffering from whole-body cyanosis and was still aware of the above symptoms. On arrival at the hospital, his respiration rate was 18 breaths/minute, and his SpO2 ranged from 80% to 85% on 15 L/minute of oxygen by mask (2.5 hours postexposure). Arterial blood gas testing revealed a methemoglobin level of 23.1%. After the administration of methylene blue, the patient’s methemoglobin level normalized and his symptoms improved. Chest X-ray and chest computed tomography showed no evidence of pulmonary edema or interstitial pneumonia, and no other abnormal findings were observed. RNA sequencing was performed on the blood samples obtained at the time of the visit, with the blood sample collected on day 5 used as a control. To our knowledge, the present study is the first to describe the analysis of RNAs from the whole blood of a patient with methemoglobinemia. The RNA sequencing analysis showed that an activated “hydrogen peroxide catabolic process” may be associated with the pathogenesis of methemoglobinemia. Conclusion The results reported in the present study may explain the pathogenesis of methemoglobinemia.

BackgroundThe novel corona virus (COVID-19) pandemic occurred worldwide. Although an excessive burden was placed on emergency medical institutions treating urgent and severe patients, its impact on patient outcome remains unknown. This study aimed to assess the impact of the COVID-19 pandemic in 2021 on the emergency medical services (EMS) system and patient outcomes in Osaka Prefecture, Japan.MethodsThis was a retrospective descriptive study with a study period from January 1, 2019 to December 31, 2021. We included patients who were transported by ambulance and had cleaned data that was recorded in the ORION system. The study endpoints were the number of patients transported by ambulance and the number of deaths among these patients in each month. To assess the impact of the COVID-19 pandemic on the EMS system, the incidence rate ratio (IRR) and 95% confidence interval (CI) were calculated using 2019 as the reference year. Mortalities were evaluated based on deaths in the emergency department and deaths at 21 days after hospitalization.ResultsThe numbers of patients transported by ambulance were 500,194 in 2019, 443,321 in 2020 (IRR: 0.88, 95% CI: 0.87–0.88), and 448,054 in 2021 (IRR: 0.90, 95% CI: 0.89–0.90). In 2019, the number of patients transported by ambulance and who died in the emergency departments was 4,980, compared to 5,485 in 2020 (IRR: 1.10, 95% CI; 1.06–1.44) and 5,925 in 2021 (IRR: 1.19, 95% CI: 1.15–1.24). In 2019, the number of patients who died within 21 days after hospitalization was 11,931, compared to 11,913 in 2020 (IRR; 1.00, 95% CI; 0.98–1.03) and 13,376 in 2021 (IRR; 1.12, 95% CI; 1.09–1.15).ConclusionThe COVID-19 pandemic decreased the number of ambulance requests and worsened mortality of patients transported by ambulance in Osaka Prefecture during 2021.

Objectives The COVID-19 pandemic might have affected emergency medical services transports for self-harm in Japan. However, the available data are insufficient to fully understand the pandemic’s impact on ambulance transports due to self-harm. This study aimed to investigate the change in the incidence of ambulance transports for self-harm from 2018 to 2021 and to identify vulnerable age groups during the pandemic.Design A population-based observational study using a database from the Osaka Prefectural Government.Setting The database covers the entire area of Osaka Prefecture and included information on ambulance transports and hospital details.Participants Ambulance transport of patients due to self-harm from 2018 through 2021 was investigated.Primary outcome measures The primary outcome was the incidence of ambulance transport for self-harm.Results We analysed 10 843 patients. Their median age was 38 years, and 69.0% were female. We observed an increasing trend of the incidence rate in cases per 100 000 population per year from 29.4 in 2018 to 31.2 in 2021. However, after adjusting for age group, sex and month, there was no difference in the incidence of ambulance transport due to self-harm in 2019 (adjusted incidence rate ratio (aIRR) 1.007; 95% CI 0.955 to 1.063), 2020 (aIRR 1.041; 95% CI 0.987 to 1.098) and 2021 (aIRR 1.022; 95% CI 0.968 to 1.078), compared with 2018. We observed no difference in 21-day mortality from 2018 through 2021. In the age group of 20–29 years, despite no difference in 2019 compared with 2018, we found an 11.7% increase in the incidence of ambulance transport due to self-harm in 2020 (aIRR 1.117; 95% CI 1.002 to 1.245) and no difference in 2021.Conclusions There was no difference in the incidence of ambulance transport due to self-harm and 21-day mortality from 2018 through 2021. However, the incidence rate of ambulance transport due to self-harm in 2020 increased in the age group of 20–29 years.

Abstract The purpose of this study was to describe the characteristics of published international literature using the Japan Trauma Data Bank (JTDB). We undertook a scoping review of studies using data from JTDB. We carried out a systematic search of the following databases on November 21, 2022, using search terms that covers trauma registries in Japan: MEDLINE, Web of Science, CINAHL, and Cochrane Library. Two authors independently abstracted the data. We included all original articles written in English. We identified 166 studies from the 456 included articles. From 2010 to 2016, the annual number of published articles was less than 10. In 2017, there were 10 articles published (6.0%). This increased to 18 (10.8%) in 2018, 21 (12.7%) in 2019, 28 (16.9%) in 2020, 33 (19.9%) in 2021, and 37 (22.3%) in 2022. Most articles (n = 138, 83.1%) reported in‐hospital mortality as the primary outcome. There were more articles on the adult population (n = 86, 51.8%) than those on the pediatric population (n = 21, 12.7%). Twenty‐one articles (12.7%) specified a mechanism of injury for the study population, and three articles (1.8%) focused on burns. Most articles did not specify injury sites for the study population (n = 108, 65.1%) and the most common injury site described in publications was the head (n = 21, 12.7%), followed by the abdomen (n = 13, 7.8%). We observed an increase in international publications using the JTDB and highlighted the major topics and knowledge gaps. Our findings could encourage studies to explore less studied areas in research using the JTDB.

Aim The nationwide impact of the coronavirus disease (COVID‐19) pandemic on major trauma in Japan is unknown. The nationwide registry‐based data of the Japanese Trauma Data Bank were analyzed to elucidate the impact of COVID‐19 on the epidemiology, treatment, and outcomes of major trauma patients. Methods Among patients transported directly from the injury site by ambulance with an Injury Severity Score of ≥16, we compared patients managed from April to December in 2019 to those managed from April to December in 2020. Results In total, 9792 patients were included in this study (2019, n = 5194; 2020, n = 4598). There were no significant differences in age or sex, but there were significant differences between 2019 and 2020 in the rates of “self‐injury (suicide)”, “motor vehicle accident”, “fall from height”, “fall down”, and “fall to the ground”, which are factors associated with patient age. Injury severity in 2019 and 2020 did not differ to a statistically significant extent, but the rate of major spinal injury increased. The time of prehospital care significantly increased in 2020 compared to 2019. There was no noticeable change in hospital treatment or in‐hospital mortality between 2019 and 2020. Conclusion This study suggests that the COVID‐19 pandemic might have altered the injuries of major trauma; however, medical services for major trauma were well supplied in Japan in 2020.

Abstract Aim The impact of the coronavirus disease (COVID‐19) pandemic on the emergency medical service system in Japan has not been fully revealed. The purpose of this study was to determine the impact of the COVID‐19 pandemic in 2021 on the difficulty in hospital acceptance of patients and patient outcome in Osaka Prefecture. Methods This study was a descriptive epidemiological study with a 3‐year study period from January 2019 to December 2021. We included patients who were transported by ambulance and had registered in the Osaka Emergency Information Research Intelligent Operation Network (ORION) system. The primary end‐point of this study was the difficulty in hospital acceptance by month, and the secondary outcome was the mortality of patients who experience difficulty in hospital acceptance in each year. Results We included 1,302,646 cases in this study. The proportion of cases with difficulty in hospital acceptance was 2.74% (12,829/468,709) in 2019, 3.74% (15,527/414,987) in 2020, and 5.09% (21,311/418,950) in 2021. The crude odds ratio for 2020 was 1.38 (95% confidence interval, 1.35–1.41) and for 2021 was 1.90 (95% confidence interval, 1.86–1.95). In 2019, 218 patients with difficulty in hospital acceptance had died by 21 days after hospitalization, whereas the number increased to 405 in 2020 and 750 in 2021. Conclusion The number of patients experiencing difficulty in hospital acceptance during the COVID‐19 pandemic in Osaka Prefecture increased, and patient outcomes were worse than before the pandemic.

Abstract The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

Abstract 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; I 2 = 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; I 2 = 45.6%). We thus believe that probiotics administration is effective in reducing the incidence of diarrhea in ventilated critically ill ICU patients.

Abstract Background There is a paucity of information for predicting patient outcomes other than the American Association for the Surgery of Trauma (AAST) renal injury scale. The aim of this study was to evaluate the association between the patient characteristics and outcomes of patients with blunt renal trauma using a nationwide database in Japan. Methods We performed a retrospective analysis of the Japan Trauma Data Bank (JTDB) from 2004 to 2018. We identified patients with blunt renal trauma by AIS codes converted to AAST grades. We evaluated trends in patient characteristics and management and assessed factors associated with mortality and nephrectomy using a multivariable logistic regression analysis. Results We identified 3550 patients with blunt renal trauma. Their median age was 43 years and 74.2% were male. Nephrectomy was performed in 3.8%, and the overall mortality rate was 9.5%. We found increasing trends in age and emergency abdominal angiography and decreasing trends in nephrectomy and mortality over the 15-year period. The following factors were associated with mortality: age ≥ 65 years (adjusted OR 3.36); pedestrian accident (adjusted OR 1.94); fall from height (adjusted OR 1.91); shock on arrival (adjusted OR 4.02); concomitant injuries to the head/neck (adjusted OR 3.14), pelvis/lower-extremity (adjusted OR 1.59), liver (adjusted OR 1.68), spleen (adjusted OR 1.45), and gastrointestinal tract (adjusted OR 1.90); AAST grades III–V (adjusted ORs 1.42, 2.16, and 5.55); and emergency abdominal angiography (adjusted OR 0.70). The following factors were associated with nephrectomy: shock on arrival (adjusted OR 1.98), concomitant injuries to the thorax (adjusted OR 0.46) and spleen (adjusted OR 2.07), AAST grades III, IV, and V (adjusted ORs 18.40, 113.89, and 468.17), and emergency abdominal angiography (adjusted OR 0.28). Conclusions We demonstrated that the AAST grade and emergency angiography were associated with mortality and nephrectomy in blunt renal trauma in the Japanese population.

Abstract Background Neutrophil extracellular traps (NETs) are fibrous structures released from activated neutrophils. NET formation has been reported to be associated with acute respiratory distress syndrome (ARDS). However, there are no reports dealing with serial changes of NET formation in tracheal aspirate of ARDS patients. Case presentation We report three cases of ARDS. Case 1 is a 69-year-old man with necrotizing fasciitis of the buttocks, case 2 is a 49-year-old woman with extensive burns (80% of total body surface), and case 3 is a 73-year-old woman with severe bacterial pneumonia. We found abundant expression of citrullinated histone H3 (Cit-H3) and the formation of NETs at the onset of ARDS in all cases. The amounts of Cit-H3 and NETs decreased with the amelioration of respiratory failure in cases 1 and 2. In case 2, the amounts of Cit-H3 and NETs increased with aggravation of infection and respiratory status. In case 3, the abundant expression of Cit-H3 and NETs persisted; the patient did not recover from ARDS and eventually died. Cit-H3 and NETs were found in tracheal aspirates even if the patients had no direct injury to the lung as in cases 1 and 2. Conclusions In these three cases, the formation of NETs was observed in tracheal aspirate of patients with ARDS by either direct or indirect insults to the lung. The amount of NET formation changed dynamically over the clinical course of each patient.

BackgroundEarly 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. ObjectiveWe aimed to assess the relationship between seasonal influenza and the frequency of mobile app use among children in Osaka Prefecture, Japan. MethodsThis 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. ResultsWe 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

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.

Aim 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. Methods 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. Results 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). Conclusions 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.

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.

Abstract The regional oxygen saturation (rSO₂) values of brain and muscle tissues can be measured simultaneously even if blood pressure cannot be measured due to circulatory failure associated with shock and may continuously reflect the oxygen supply‐demand balance.

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

BackgroundWhen 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. ObjectiveThe purpose of this study was to clarify the use profile of this mobile app based on data usage in the app. MethodsThis 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. ResultsThe 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%). ConclusionsThis study clarified the profile of use of a self-triage app for pediatric emergency patients in Japan.

Abstract Background Air in the venous system may cause vascular air embolism, which is a potentially life-threatening event. The presence of air in venous system after basilar skull fracture is very rare. Case presentation A 77-year-old man fell from a truck bed and suffered head and neck trauma. On hospital arrival, his consciousness was clear and his vital signs were stable. His chief complaint was pain in the back of his head and neck. Head CT showed traumatic subarachnoid hemorrhage in the right frontal area and basilar skull fracture of the occipital bone. Whole body CT showed pneumocephalus and air in the jugular vein and right ventricle. The patient was placed in the supine position in a state of absolute rest to prevent vascular air embolism and was treated conservatively. On hospital day 3, CT was reperformed, revealing disappearance of air in the right ventricle and decreased air in the veins of the head and neck. On hospital day 4, the air in the veins disappeared completely on CT. He did not experience vascular air embolism after increasing of his activity level (e.g., raising his head on hospital day 3 and standing and walking alone on day 5). He was discharged 34 days after admission without sequelae. Conclusions Head trauma patients with basilar skull fracture might develop vascular air embolism if physicians fail to detect air in the venous system on hospital arrival. A high degree of suspicion regarding air in venous system or heart is required when patients present with such injuries.

Background: Hereditary angioedema (HAE) is a rare but life-threatening condition. HAE types I and II (HAE-1/2) result from C1-inhibitor (C1–INH) deficiency. However, recent genetic analysis has established a new type of HAE with normal C1–INH (HAEnC1-INH). The mutations of factor XII, plasminogen, angiopoietin 1, and kininogen 1 genes may be the cause of HAEnC1-INH. Nevertheless, other causative molecules (HAE-unknown) may be involved. The Japanese therapeutic environment for HAE has been improving owing to the self-subcutaneous injection of icatibant, which was approved for the treatment of acute attack and enables early therapy. Erythema marginatum (EM) is a visible prodromal symptom which occasionally occurs prior to an angioedema attack; hence, recognizing the risk of an acute attack is important for early treatment. However, the detailed characteristics of EM remain unclear. In this study, we first investigated the clinical manifestations of EM in Japanese patients with HAE. Methods: A 20-point survey was developed and distributed to 40 physicians to gather clinical data on EM from patients with HAE. Results: Data on 68 patients with HAE (58 patients with HAE-1/2 and 10 patients with HAE-unknown) were collected. Of the patients with HAE-1/2, 53.4% experienced EM, whereas 43.1% did not. The forearm was the most frequent area of EM (64.5%), followed by the abdomen (29.0%) and upper arm and precordium (19.3%). Of the HAE-1/2 patients with EM, 41.9% always had angioedema following EM, while 29.0% always had colocalization of EM with angioedema. Moreover, 3.2% showed a correlation between the awareness of EM and severity of an angioedema attack. In 60.9% of HAE-1/2 patients with EM, the interval between the awareness of EM and appearance of angioedema was

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 R2, regression coefficients and 95% confidence interval (CI) using interrupted time series analysis. Results This study included 148,873 patients. The R2 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

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

BackgroundReplacing 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.MethodsThis 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 R2 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 R2 between the predicted weekly number of influenza patients from the linear regression model and the actual weekly number of influenza patients for influenza outbreak season (December-April).ResultsThere 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 R2 and adjusted R2 were 0.869 and 0.842, respectively. The Spearman rank-order coefficient was 0.923 (PConclusionWe revealed a positive relationship in this population between the number of influenza patients and the number of telephone triages for fever.

Abstract 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

Abstract Background and purpose The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc. This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. Methods Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. Results A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs. Conclusions Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

Bovine leukemia virus (BLV) causes enzootic bovine leukosis, a malignant form of B-cell lymphoma, and is closely related to human T-cell leukemia viruses. We investigated whether BLV infection affects host genes associated with DNA mismatch repair (MMR). Next-generation sequencing of blood samples from five calves experimentally infected with BLV revealed the highest expression levels of seven MMR genes (EXO1, UNG, PCNA, MSH2, MSH3, MSH6, and PMS2) at the point of peak proviral loads (PVLs). Furthermore, MMR gene expression was only upregulated in cattle with higher PVLs. In particular, the expression levels of MSH2, MSH3, and UNG positively correlated with PVL in vivo. The expression levels of all seven MMR genes in pig kidney-15 cells and the levels of PMS2 and EXO1 in HeLa cells also increased tendencies after transient transfection with a BLV infectious clone. Moreover, MMR gene expression levels were significantly higher in BLV-expressing cell lines compared with those in the respective parental cell lines. Expression levels of MSH2 and EXO1 in BLV-infected cattle with lymphoma were significantly lower and higher, respectively, compared with those in infected cattle in vivo. These results reveal that BLV infection affects MMR gene expression, offering new candidate markers for lymphoma diagnosis.

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.

Neutrophil extracellular traps (NETs), a newly identified immune mechanism, are induced by inflammatory stimuli. Modification by citrullination of histone H3 is thought to be involved in the in vitro formation of NETs. The purposes of this study were to evaluate whether NETs and citrullinated histone H3 (Cit-H3) are present in the bloodstream of critically ill patients and to identify correlations with clinical and biological parameters. Blood samples were collected from intubated patients at the time of ICU admission from April to June 2011. To identify NETs, DNA and histone H3 were visualized simultaneously by immunofluorescence in blood smears. Cit-H3 was detected using a specific antibody. We assessed relationships of the presence of NETs and Cit-H3 with the existence of bacteria in tracheal aspirate, SIRS, diagnosis, WBC count, and concentrations of IL-8, TNF-α, cf-DNA, lactate, and HMGB1. Forty-nine patients were included. The median of age was 66.0 (IQR: 52.5-76.0) years. The diagnoses included trauma (7, 14.3%), infection (14, 28.6%), resuscitation from cardiopulmonary arrest (8, 16.3%), acute poisoning (4, 8.1%), heart disease (4, 8.1%), brain stroke (8, 16.3%), heat stroke (2, 4.1%), and others (2, 4.1%). We identified NETs in 5 patients and Cit-H3 in 11 patients. NETs and/or Cit-H3 were observed more frequently in "the presence of bacteria in tracheal aspirate" group (11/22, 50.0%) than in "the absence of bacteria in tracheal aspirate" group (4/27, 14.8%) (p