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Abstract Disseminated intravascular coagulation (DIC) is a frequent but lethal complication in sepsis. Anticoagulant therapies, such as heparin, antithrombin, activated protein C, and recombinant human‐soluble thrombomodulin, were expected to regulate the progression of coagulopathy in sepsis. Although a number of randomized controlled trials (RCTs) have evaluated the survival effects of these therapies over the past few decades, there remains no consistent evidence showing a significant survival benefit of anticoagulant therapies. Currently, anticoagulant therapies are not conducted as a standard treatment against sepsis in many countries and regions. However, most of these RCTs were performed overall in patients with sepsis but not in those with sepsis‐induced DIC, who were theoretically the optimal target population of anticoagulants. Actually, multiple lines of evidence from observational studies and meta‐analyses of the RCTs have suggested that anticoagulant therapies might reduce mortality only when used in septic DIC. In addition, the severity of illness is another essential factor that maximally affects the efficacy of the therapy. Therefore, to provide evidence on the true effect of anticoagulant therapies, the next RCTs must be designed to enroll only patients with sepsis‐induced overt DIC and a high severity of illness. To prepare these future RCTs, a novel scientific infrastructure for accurate detection of patients who can receive maximal benefit from anticoagulant therapies also needs to be established.

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 This study aimed to investigate the association of early vasopressor initiation with improved septic shock outcomes. Methods This multicenter observational study was conducted in 17 intensive care units in Japan and included adult patients with sepsis admitted to the intensive care unit from July 2019 to August 2020 and treated with vasopressor therapy. Patients were divided into the early vasopressor group (≤1 h from sepsis recognition) and the delayed vasopressor group (>1 h). The impact of early vasopressor administration on risk‐adjusted in‐hospital mortality was estimated using logistic regression analyses adjusted by an inverse probability of treatment weighting analysis with propensity scoring. Results Among the 97 patients, 67 received vasopressor therapy within 1 h from sepsis recognition and 30 received vasopressor after 1 h. In‐hospital mortality was 32.8% in the early vasopressor group and 26.7% in the delayed vasopressor group (p = 0.543). The adjusted odds ratio for in‐hospital mortality was 0.76 (95% confidence interval 0.17–3.29) when comparing patients in the early vasopressor with those in the delayed vasopressor group. The fit curve from the mixed‐effects model showed a relatively lower trend toward an infusion volume over time in the early vasopressor group than in the delayed vasopressor group. Conclusion Our study did not reach a definitive conclusion for early vasopressor administration. However, early vasopressor administration may help avoid volume overload in the long course of sepsis care.

Aim To clarify the immune cellular changes in critically ill patients recovering from coronavirus disease 2019 (COVID‐19). Methods The immune response of peripheral blood mononuclear cells from patients with severe COVID‐19 in different stages of recovery (3, 6, and 12 months from hospitalization) was evaluated by single‐cell mass cytometry. Immunological changes in patients were compared with those in age‐matched healthy donors. Results Three patients with severe COVID‐19 were compared with four healthy donors. In the patients, there was an increase in the cell density of CD4‐ and CD8‐positive T lymphocytes, and B cells, over the course of the recovery period. CD4‐ and CD8‐positive T lymphocytes expressing T‐bet and granzyme B (Gzm B) in patients were abundant during all recovery periods. The level of regulatory T cells remained high throughout the year. The levels of natural killer (NK) cells in patients were higher than in those in the healthy donors, and the frequency of CD16+ NK cells expressing Gzm B increased throughout the year. Conclusion Patients recovering from severe COVID‐19 showed persistence of cytotoxic lymphocytes, NK cells, and regulatory T cells throughout the posthospitalization year of recovery.

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.

Disseminated intravascular coagulation (DIC) is a frequent complication in sepsis. Once patients develop DIC, the mortality rate increases significantly. Moreover, recent studies have suggested that coagulation disorder plays a significant role in the development of organ dysfunction in sepsis. Thus, the early detection of DIC is vital in sepsis care, and the Japanese Association for Acute Medicine established a set of original diagnostic criteria in 2006 (JAAM DIC). Since then, the usefulness of the JAAM DIC has been repeatedly reported, and these criteria have been widely adopted in emergency and critical care settings in Japan. Different criteria have also been released by the International Society on Thrombosis and Haemostasis (ISTH overt‐DIC), and the latter criteria are presently considered to be the international standard. Compared with the JAAM DIC, the ISTH overt‐DIC criteria are stricter and the timing of diagnosis is later. This discrepancy is because of conceptual differences. As many physicians think sepsis‐associated DIC is the target of anticoagulant therapies in Japan, the JAAM DIC criteria were designed to allow the early initiation of treatment. As other countries do not provide DIC‐specific treatments, early diagnosis is not necessary, and this situation has led to a significant gap. However, as overt‐DIC is a late‐phase coagulation disorder, a need for early detection has been advocated, and members of the ISTH have recently proposed the category of sepsis‐induced coagulopathy. In this review, we introduce the strengths and weaknesses of the major criteria including JAAM‐DIC, ISTH overt‐DIC, sepsis‐induced coagulopathy, and Japanese Society on Thrombosis and Haemostasis‐DIC.

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

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.

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