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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remained a major global health concern in 2021. To suppress the spread of infection, mass vaccinations have been performed across countries worldwide. In Japan, vaccinations of the first and second doses for most of the nation were performed during the nationwide outbreak of the B.1.617.2 (Delta) variant with the L452R spike protein mutation, and the effectiveness of the vaccinations to suppress the spread of COVID-19 among the people in Japan remains uncertain. In this study, adults aged ≥18 years, who were in contact with patients with COVID-19 and underwent nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) tests during August and September 2021 at a mass screening test center in Japan, were enrolled. In this period, more than 95% of the COVID-19 infections were reportedly caused by the Delta variant. As a result, a total of 784 adults with recent contact history, including 231 (29.5%) RT-PCR test-positive cases, were enrolled. The test positivity rate was lower in individuals who had been vaccinated twice than in unvaccinated individuals (12.5% vs. 39.0%, p0.0001), with the risk ratio of 0.32 (95% confidence interval 0.23-0.46). The vaccine effectiveness was the highest between 7-90 days after the second vaccine dose. In conclusion, two doses of mRNA COVID-19 vaccines effectively suppressed transmission in Japan during the nationwide pandemic of the Delta variant, estimated to have prevented 50-80% of the infection.

Background: Endovascular therapy within an appropriate time has been shown to improve neurological outcomes in patients with ischemic stroke. A hybrid emergency room is an emergency unit that can be used for resuscitation, computed tomography (CT), surgery, and angiography. Therefore, immediate CT and endovascular therapy can be performed without transfer to other rooms. We aimed to evaluate the possibility of using a hybrid emergency room to shorten the time to endovascular therapy in patients with ischemic stroke.Methods: This was a single-institutional, retrospective, and observational study. Patients with acute ischemic stroke who underwent endovascular therapy in the hybrid emergency room between May 2018 and May 2020 were included in the study. The main outcome was door-to-puncture time. The secondary outcomes were door-to-reperfusion and onset-to-puncture time. Descriptive statistics were also calculated. Outcome times were compared with those recommended by recent guidelines.Results: Twenty-seven patients were included in this analysis. The median age was 77 (69–83) years. The median National Institutes of Health Stroke Scale score on admission was 15 (10–21.25), while the median door-to-puncture, door-to-reperfusion, and onset-to-puncture times were 45 (29–63), 140 (100–170), and 120 (71–224) minutes, respectively. The door-to-puncture time was within the recommended time of 60 minutes for approximately 75% of the patients.Conclusions: The door-to-puncture time in our study was shorter than that recommended by the guidelines. Acute ischemic stroke management in a hybrid emergency room could shorten door-to-puncture time, which may contribute to improving patients’ neurological outcomes.

Objective Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), remains the world's largest public health concern in 2021. A history of close contact with infectious patients is a factor that predicts a positive SARS-CoV-2 test result. Meanwhile, the precise predictive value of symptoms suggestive of COVID-19 has not been fully elucidated. This study aimed to clarify the predictive and discriminatory value of each clinical symptom suggestive of COVID-19. Methods This study enrolled participants who were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction using a nasopharyngeal swab between November 2020 and January 2021. All enrolled patients were evaluated for data regarding the presence and closeness of contact with infectious patients and comprehensive clinical features (i.e., fever, cough, dyspnea, fatigue, dysosmia, and dysgeusia). Results Among the 1,744 tested participants, 144 tested positive for SARS-CoV-2. In the test-positive group, self-reported cough, fatigue, dysosmia, and dysgeusia were significant predictors of COVID-19, independent from a history of close contact. In particular, the presence of dysosmia was the strongest predictor of COVID-19 in both univariate and multivariate analyses. Among the 42 patients with self-reported dysosmia, 25 (59.5%) were SARS-CoV-2 test-positive. Self-reported dysosmia was reported by 25 (17.4%) of the 144 patients who tested positive for SARS-CoV-2, and 15 (60.0%) of the 25 COVID-19 patients with dysosmia had accompanying dysgeusia. Conclusion The presence of dysosmia was reported by 10-25% of patients with COVID-19, and is a significant predictor of COVID-19 infection, independent from a history of close contact.

Hypothermia has been shown to be associated with a high mortality rate among patients with sepsis. However, the relationship between hypothermia and body mass index (BMI) with respect to mortality remains to be elucidated. We conducted this study to assess the association between hypothermia and survival outcomes of patients with sepsis according to BMI categories. This secondary analysis of a prospective cohort study enrolled 1184 patients (aged ≥ 16 years) with sepsis hospitalized in 59 intensive care units in Japan. Patients were divided into 3 BMI categories (18.5 [low], 18.5-24.9 [normal],24.9 [high] kg/m2) and 2 body temperature (36 °C and ≥ 36 °C) groups. The primary outcome was in-hospital mortality rate. Associations between hypothermia and BMI categories with respect to in-hospital mortality were evaluated using multivariate logistic regression analysis. Of the 1089 patients, 223, 612, and 254 had low, normal, and high BMI values, respectively. Patients with body temperature 36 °C (hypothermia) had a higher in-hospital mortality rate than that had by those without hypothermia in the normal BMI group (25/63, 39.7% vs. 107/549, 19.5%); however, this was not true for patients in the low or high BMI groups. A significant interaction was observed between hypothermia and normal BMI for in-hospital mortality (odds ratio, 1.56; 95% confidence interval, 1.00-3.41; P value for interaction = .04); however, such an interaction was not found between hypothermia and low or high BMIs. Patients with sepsis and hypothermia in the normal BMI subgroup may have a higher mortality risk than that of those in the low or high BMI subgroups and, therefore, require more attention.

BACKGROUND: Little guidance exists for the treatment of pseudoaneurysm following pediatric blunt liver and/or spleen injuries (BLSI). We aimed to describe the incidence of delayed pseudoaneurysm development and the subsequent clinical course of pseudoaneurysm in pediatric BLSI. METHODS: This multicenter retrospective cohort study from Japan included pediatric patients (≤16 years old) who sustained BLSI from 2008 to 2019. The cohort was divided into four groups based on hemostatic intervention within 48 hours of admission, namely non-operative management (NOM), NOM with interventional radiology (IR), operative management (OM), and combined IR/OM. Descriptive statistics were used to describe the incidence of delayed pseudoaneurysm among the groups and to characterize the clinical course of any pseudoaneurysms. RESULTS: A total of 1, 407 children (median age, 9 years) from 83 institutions were included. The overall number (incidence) of cases of delayed pseudoaneurysm formation was 80 (5.7%), and the number with delayed pseudoaneurysm rupture was 16 (1.1%) cases in the entire cohort. Patients treated with NOM (1056), NOM with IR (276), OM (53), and combined IR/OM (22) developed 43 (4.1%), 32 (12%), 2 (3.8%), and 3 (14%) delayed pseudoaneurysms, respectively. Among patients who developed any pseudoaneurysms, 39% of patients underwent prophylactic IR for unruptured pseudoaneurysm, while 13% required emergency angioembolization for delayed pseudoaneurysm rupture, with one ruptured case requiring total splenectomy. At least 45% of patients experienced spontaneous resolution of pseudoaneurysm without any interventions. CONCLUSION: Our results suggest that the risk of delayed pseudoaneurysm still exists even after acute phase IR as an adjunct to NOM for BLSI in children, indicating the necessity of a period of further observation. While endovascular interventions are usually successful for pseudoaneurysm management, including rupture cases, given the high incidence of spontaneous resolution, the ideal management of pseudoaneurysm remains to be investigated in future studies. LEVEL OF EVIDENCE: Level 4; Therapeutic/Care management.

Background The clinical frailty scale (CFS) score has been validated as a predictor of adverse outcomes in community-dwelling older people. Older people are at a higher risk of sepsis and have a higher mortality rate. However, the association of frailty on outcomes in patients with sepsis has not been completely examined. Objective This study evaluated the association between CFS and outcomes in patients with sepsis. Design This was a multicenter prospective cohort substudy. Settings and participants The study included 37 emergency departments from across Japan. The patients (age ≥16 years) were included in this study if they had suspected infection at an emergency department during December 2017-February 2018. Outcome measure and analysis The primary outcome was 28-day mortality, stratified by the CFS score categories. The secondary outcomes were the duration of hospital stay, number of ICU-free days (ICUFDs) and number of ventilator-free days (VFDs). Main results A total of 917 patients were included. The median age was 79 years. The CFS score was associated with an increased risk of 28-day mortality and with a higher likelihood of long-term hospital stay and short-term VFDs and ICUFDs. Multivariate logistic regression analysis indicated that the CFS score was a predictor of 28-day mortality [odds ratio (OR), 1.26; 95% confidence interval (CI), 1.11-1.42]. Conclusions This study reported that in patients with suspected sepsis in the emergency department, frailty may be associated with poor prognosis and length of hospital stay.

The exact profiles of the clinical symptoms related to the SARS-CoV-2 Omicron variant (B.1.1.529) remain largely uncertain. Therefore, this study aimed to clarify the clinical manifestations of infection with this variant. We enrolled individuals who were tested by quantitative nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) test at a large screening center in a city of Japan during the B.1.1.529 Omicron variant wave between January and May 2022, after contact with COVID-19 patients. Swab tests were planned to be performed approximately 4-5 days after contact. The presence of COVID-19-related symptoms was assessed at the swab test site. Among the 2,507 enrolled individuals, 943 (37.6%) were RT-PCR test-positive and 1,564 (62.4%) were test-negative. Among the 943 PCR test-positive participants, the prevalence of the symptoms was as follows: 47.3% with cough, 32.9% with sore throat, 18.4% with fatigability, 12.7% with fever of ≥ 37.5℃, 9.9% with dyspnea, 2.1% with dysosmia, and 1.4% with dysgeusia. The prevalence of cough, sore throat, dyspnea, and fatigability was higher among adults aged ≥ 18 years than among children and adolescents. The prevalence of dysosmia and dysgeusia remarkably decreased during the Omicron wave (1-3%) compared to during the pre-Omicron variant waves (15-25%). In summary, common COVID-19-related symptoms during the Omicron variant wave included cough and sore throat, followed by fatigability, fever, and dyspnea. The prevalence of most of these symptoms was higher in adults than in non-adults. The prevalence of dysosmia and dysgeusia remarkably decreased with the Omicron variant than with pre-Omicron variants.

The administration of a third booster dose of messenger ribonucleic acid (mRNA) vaccines against coronavirus disease 2019 (COVID-19) has progressed worldwide. Since January 2022, Japan has faced a nationwide outbreak caused by the Omicron variant, which occurred simultaneously with the progression of mass vaccination with the third booster dose. Therefore, this study evaluated the effectiveness of the third dose of vaccine by reverse transcription-polymerase chain reaction (RT-PCR) test using nasopharyngeal swab samples from adults aged ≥ 18 years tested after having close contact with COVID-19 cases between January and May 2022. Participants who completed only one dose were excluded from the study. Among the 928 enrolled participants, 139 had never been vaccinated, 609 had completed two doses, 180 had completed three doses before the swab test, and the overall RT-PCR test positivity rate in each group was 48.9%, 46.0%, and 32.2%, respectively. The vaccine effectiveness of the third dose to prevent infection after close contact was approximately 40% (95% confidence interval: 20–60%), which was the highest at 10–70 days after receiving the third dose. In conclusion, the effectiveness of the three-dose mRNA COVID-19 vaccine after close contact during the Omicron outbreak is approximately 40%.

Background: Traumatic pulmonary pseudocysts are caused after thoracic trauma. They do not usually require specific therapy when no complications arise, such as infection and bleeding. Complicated pulmonary pseudocysts, however, can be life threatening and require specific treatment. Although treatments of systemic antibiotics and surgery for infected cysts have been reported, to our knowledge, there are no reports on aerosolized antibiotics therapy for infected traumatic pulmonary pseudocysts.Case presentation: We present the case of a 31-year-old woman who was severely injured and suffered a blunt thoracic trauma in a vehicular accident crash, and required ventilator management in a previous hospitalization. Seven days later, she developed acute respiratory distress syndrome and was transferred to our department. We were unable to maintain proper oxygenation with ventilator management alone and established venous–venous extracorporeal membrane oxygenation. She then developed persistent bacteremia of Pseudomonas aeruginosa owing to infected traumatic pulmonary pseudocysts. On the 21st day of her hospitalization, the drainage for the enlarged cyst led to minor improvements in her respiratory condition. On the 32nd day of hospitalization, in addition to systemic antibiotics therapy, the aerosolized antibiotics therapy (inhalation of tobramycin (135 mg) every 12 h) was administered for the treatment of resistant infected pseudocysts. Her respiratory condition gradually improved, and the infected pseudocysts shrank. On the 43rd day of hospitalization, she was successfully removed extracorporeal membrane oxygenation.Conclusions: Aerosolized antibiotics therapy may be a potential option for patients with infected traumatic pulmonary pseudocysts when conventional therapies are not successful.

This study aimed to investigate the relationship between transient return of spontaneous circulation (ROSC) before extracorporeal membrane oxygenation (ECMO) initiation and outcomes in out-of-hospital cardiac arrest (OHCA) patients, who were resuscitated with extracorporeal cardiopulmonary resuscitation (ECPR).This study was a secondary analysis of the SAVE-J II study, which was a retrospective multicentre registry study involving 36 participating institutions in Japan. We classified patients into two groups according to the presence or absence of transient ROSC before ECMO initiation. Transient ROSC was defined as any palpable pulse of ≥1 min before ECMO initiation. The primary outcome was favourable neurological outcomes (cerebral performance categories 1-2).Of 2,157 patients registered in the SAVE-J II study, 1,501 met the study inclusion criteria; 328 (22%) experienced transient ROSC before ECMO initiation. Patients with transient ROSC had better outcomes than those without ROSC (favourable neurological outcome, 26% vs 12%,In OHCA patients resuscitated with ECPR, transient ROSC before ECMO initiation was associated with favourable outcomes. Hence, transient ROSC is a predictor of improved outcomes after ECPR.

The survival rate of patients with critical coronavirus disease-19 (COVID-19) over time is inconsistent in different settings. In Japan, a national database was organized to monitor and share the patient generation across the country in an immediate response to the COVID-19 pandemic. This study aimed to evaluate changes in survival over time and the prognostic factors in critical COVID-19 patients receiving mechanical ventilation with/without extracorporeal membrane oxygenation (ECMO) using the largest database in Japan.This is a prospective observational cohort study of patients admitted to intensive care units in Japan with fatal COVID-19 pneumonia receiving mechanical ventilation and/or ECMO. We developed a prospective nationwide registry covering 80% of intensive care units in Japan, and analyzed the association between patients' backgrounds, institutional ECMO experience, and timing of treatment initiation and prognosis between February 2020 and November 2021. Prognostic factors were evaluated by Kaplan-Meier analysis and Cox proportional hazards analysis.A total of 9418 patients were ventilated, of whom 1214 (13%) received ECMO. The overall survival rate for ventilated patients was 79%, 65% for those receiving ECMO. There have been five outbreaks in Japan to date. The survival rate of ventilated patients increased from 76% in the first outbreak to 84% in the fifth outbreak (p 0.001). The survival rate of ECMO patients remained unchanged at 60-68% from the first to fifth outbreaks (p = 0.084). Age of ≥ 59 (hazard ratio [HR] 2.17; 95% confidence interval [CI] 1.76-2.68), ventilator days of ≥ 3 before starting ECMO (HR 1.91; 95% CI 1.57-2.32), and institutional ECMO experiences of ≥ 11 (HR 0.70; 95% CI 0.58-0.85) were independent prognostic factors for ECMO.During five COVID-19 outbreaks in Japan, the survival rate of ventilated patients tended to have gradually improved, and that of ECMO patients did not deteriorate. Older age, longer ventilator days before starting ECMO, and fewer institutional ECMO experiences may be independent prognostic factors for critical COVID-19 patients receiving ECMO.

Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, or their combination. The increases in the risk of hospital mortality were suppressed in the high-DIC-score patients aged 60–70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk of hospital mortality in patients aged 50–60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60–70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis.

Background There is no one-size-fits-all empiric antimicrobial therapy for sepsis because the pathogens vary according to the site of infection and have changed over time. Therefore, updating knowledge on the spectrum of pathogens is necessary for the rapid administration of appropriate antimicrobials. Objective The aim of this study was to elucidate the current spectrum of pathogens and its variation by site of infection in sepsis. Methods This was a prospective nationwide cohort study of consecutive adult patients with sepsis in 59 intensive care units in Japan. The spectrum of pathogens was evaluated in all patients and in subgroups by site of infection. Regression analyses were conducted to evaluate the associations between the pathogens and mortality. Results The study cohort comprised 1184 patients. The most common pathogen was Escherichia coli (21.5%), followed by Klebsiella pneumoniae (9.0%). However, the pattern varied widely by site of infection; for example, gram-positive bacteria were the dominant pathogen in bone/soft tissue infection (55.7%) and cardiovascular infection (52.6%), but were rarely identified in urinary tract infection (6.4%). In contrast, gram-negative bacteria were the predominant pathogens in abdominal infection (38.4%) and urinary tract infection (72.0%). The highest mortality of 47.5% was observed in patients infected with methicillin-resistant Staphylococcus aureus, which was significantly associated with an increased risk of death (odds ratio 1.88, 95% confidence interval 1.22–2.91). Conclusions This study revealed the current spectrum of pathogens and its variation based on the site of infection, which is essential for empiric antimicrobial therapy against sepsis.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the world's largest public health concern in 2021. This study evaluated the associations of the prevalence of airway symptoms among the tested individuals and data regarding the natural environmental factors with the weekly number of newly diagnosed COVID-19 patients in Sendai City (N

A recent randomised controlled trial failed to demonstrate a beneficial effect of recombinant human thrombomodulin (rhTM) on sepsis. However, there is still controversy in the effects of rhTM for sepsis due to the heterogeneity of the study population. We previously identified patients with a distinct phenotype that could be a potential target of rhTM therapy (rhTM target phenotype). However, for application in the clinical setting, a simple tool for determining this target is necessary. Thus, using three multicentre sepsis registries, we aimed to develop and validate a machine learning model for predicting presence of the target phenotype that we previously identified for targeted rhTM therapy. The predictors were platelet count, PT-INR, fibrinogen, fibrinogen/fibrin degradation products, and D-dimer. We also implemented the model as a web-based application. Two of the three registries were used for model development (n = 3694), and the remaining registry was used for validation (n = 1184). Approximately 8–9% of patients had the rhTM target phenotype in each cohort. In the validation, the C statistic of the developed model for predicting the rhTM target phenotype was 0.996 (95% CI 0.993–0.998), with a sensitivity of 0.991 and a specificity of 0.967. Among patients who were predicted to have the potential target phenotype (predicted target patients) in the validation cohort (n = 142), rhTM use was associated with a lower in-hospital mortality (adjusted risk difference, − 31.3% [− 53.5 to − 9.1%]). The developed model was able to accurately predict the rhTM target phenotype. The model, which is available as a web-based application, could profoundly benefit clinicians and researchers investigating the heterogeneity in the treatment effects of rhTM and its mechanisms.

Background The prevalence of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) has been increasing rapidly worldwide. However, guidelines or clinical studies do not provide sufficient data on ECPR practice. The aim of this study was to provide real-world data on ECPR for patients with OHCA, including details of complications. Methods We did a retrospective database analysis of observational multicenter cohort study in Japan. Adult patients with OHCA of presumed cardiac etiology who received ECPR between 2013 and 2018 were included. The primary outcome was favorable neurological outcome at hospital discharge, defined as a cerebral performance category of 1 or 2. Results A total of 1644 patients with OHCA were included in this study. The patient age was 18–93 years (median: 60 years). Shockable rhythm in the initial cardiac rhythm at the scene was 69.4%. The median estimated low flow time was 55 min (interquartile range: 45–66 min). Favorable neurological outcome at hospital discharge was observed in 14.1% of patients, and the rate of survival to hospital discharge was 27.2%. The proportions of favorable neurological outcome at hospital discharge in terms of shockable rhythm, pulseless electrical activity, and asystole were 16.7%, 9.2%, and 3.9%, respectively. Complications were observed during ECPR in 32.7% of patients, and the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively. Conclusions In this large cohort, data on the ECPR of 1644 patients with OHCA show that the proportion of favorable neurological outcomes at hospital discharge was 14.1%, survival rate at hospital discharge was 27.2%, and complications were observed during ECPR in 32.7%.

This study aimed to precisely describe the details of targeted temperature management (TTM) following extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA). A questionnaire to examine the TTM details following ECPR was distributed to 36 medical institutions that participated in the Study of Advanced life support for Ventricular fibrillation with Extracorporeal circulation in Japan (SAVE-J) II study. The survey was conducted using an anonymous questionnaire through the Internet and was distributed in January 2021 and collected in February 2021. Practical TTM methods (induction, maintenance, and rewarming duration) and monitoring and management methods, such as target levels, drugs, left ventricular decompression therapy, nutrition, and rehabilitation therapy, were recorded. We received responses from all 36 institutions. The target temperature was initiated at 34°C in 72.2% of institutions. In ∼90% of institutions, the maintenance duration was 24 hours, which was also the leading duration of rewarming 24 hours (38.9%), followed by 48 hours (30.6%). Electroencephalogram is routinely applied in only 13.9% of institutions. Prophylactic antibiotics were used in 58.6% of institutions. Enteral nutrition during TTM is consistently initiated in 27.8% of institutions and 33.3% of institutions initiated enteral nutrition for patients without catecholamine requirements. The 24-48 hours (55.6%) was the leading period of initiating early rehabilitation, followed by24 hours. This survey described the details of the current practice for treating patients with OHCA by TTM following ECPR. Since various factors were undetermined in the TTM, randomized controlled trials will be necessary to resolve issues during TTM following ECPR.

Background Resuscitative thoracotomy is a lifesaving procedure for trauma patients that are hemodynamically unstable. Cross-clamping of the descending thoracic aorta is an essential procedure performed during resuscitative thoracotomy in patients with impending cardiac arrest. Although complications related to resuscitative thoracotomy have been reported, there is no report on avulsion of aortic branches related to cross-clamping of the descending aorta and its appropriate management. Case presentation We present the case of a 42-year-old woman who sustained blunt trauma due to an accidental fall. The patient was hemodynamically unstable and required resuscitative thoracotomy with cross-clamping of the thoracic aorta. However, hemorrhage from avulsion of aortic branches related to aortic cross-clamping was identified. Initially, transcatheter arterial embolization was attempted to achieve hemostasis; however, when that proved ineffective, thoracic endovascular aortic repair was performed, which resulted in successful hemorrhage control without any sequelae. Conclusions Thoracic endovascular aortic repair may be a management option for aortic branch avulsion due to cross-clamping of the descending aorta during resuscitative thoracotomy.

IntroductionResuscitative endovascular balloon occlusion of the aorta (REBOA) has been used as a bridge to definitive bleeding control of subdiaphragmatic injury. Since previous observational studies have poorly adjusted for confounding factors, it is necessary to incorporate REBOA-specific and time-varying covariates in the model. We hypothesised that REBOA improves the survival of haemodynamically unstable torso trauma patients after comparing the REBOA group with a matched control group (non-REBOA group).Methods and analysisThe Japanese Association for the Surgery of Trauma-REBOA Study is a prospective, multicentre, matched cohort study organised by the Clinical Trial Committee of the Japanese Association for the Surgery of Trauma. To minimise observational study biases, this study will prospectively register traumatic shock patients who require bleeding control within 60 min upon arrival at the emergency department, with in-hospital mortality as the primary outcome. After the data set is fixed, the missing values for all variables will be imputed using the multiple imputation technique. In the primary analysis, propensity scores for the probability of REBOA decision (regardless of the actual REBOA deployment) will be calculated from the baseline information using a logistic regression generalised linear mixed-effects model, which will be performed for both the REBOA use and non-REBOA use groups.Ethics and disseminationThis study was approved by the ethics committee of each participating hospital. The results will be disseminated to the participating hospitals, submitted to peer-reviewed journals for publication and presented at congresses.Trial registration numberUMIN Clinical Trials Registry (UMIN000035458).

A recent randomised controlled trial (RCT) failed to demonstrate a beneficial effect of recombinant human thrombomodulin (rhTM) on sepsis, but there is controversy in the effects of rhTM for sepsis due to heterogeneity of its study population. While we previously identified a distinct phenotype that could be a potential target of rhTM therapy, the discovery of phenotypes itself is insufficient because rules or prediction models are required to determine which patients are the potential target phenotypes of rhTM therapy in the clinical setting. Thus, using three multicentre sepsis registries, we aimed to develop and validate a machine learning model for predicting the target phenotype that we previously identified for targeted rhTM therapy. The predictors werer platelet counts, PT-INR, fibrinogen, fibrinogen/fibrin degradation products, and D-dimer. We also implemented the model as a web-based application. Two of the three registries were used for model development (n=3694), and the remaining registry was used for validation (n=1184). Approximately 9% of patients had the target phenotype in each cohort. In the validation, the C statistic of the developed model to predict the target phenotype was 0.996 (95% CI, 0.993-0.998), with a sensitivity of 0. 991and a specificity of 0. 967. Among patients those who were predicted as “potential target phenotype” in the validation cohort, rhTM use was associated with a lower in-hospital mortality (adjusted risk difference, −31.3% [−53.5% to −9.1%]). Given the high accuracy of the developed model for predicting the target phenotype for rhTM therapy, implementing the model as a web-based application could profoundly benefit clinicians and researchers conducting subsequent investigations to address heterogeneity in the treatment effects and its mechanisms.

We report a severe case of Chromobacterium haemolyticum pneumonia associated with near-drowning and detail the investigation of the pathogen and river water. Our genomic and environmental investigation demonstrated that river water in a temperate region can be a source of C. haemolyticum causing human infections.

Multiple organ dysfunction syndrome (MODS) is a predominant cause of death in acute respiratory distress syndrome (ARDS). Disseminated intravascular coagulation (DIC) is recognized as a syndrome that frequently develops MODS. To test the hypothesis that DIC scores are useful for predicting MODS development and that DIC is associated with MODS, we retrospectively analyzed the data of a prospective, multicenter study on ARDS.Patients who met the Berlin definition of ARDS were included. DIC scores as well as the disease severity and the development of MODS on the day of the diagnosis of ARDS (day 0) and day 3 were evaluated. The primary and secondary outcomes were the development of MODS and the hospital mortality.In the 129 eligible patients, the prevalence of DIC was 45.7% (59/129). DIC patients were more seriously ill and exhibited a higher prevalence of MODS on days 0 and 3 than non-DIC patients. The DIC scores on day 0 detected the development of MODS with good area under the receiver operating characteristic curve (0.714, p.001). DIC on day 0 was significantly associated with MODS on days 0 and 3 (odds ratio 1.53 and 1.34, respectively). Patients with persistent DIC from days 0 to 3 had higher rates of both MODS on day 3 (p=.035) and hospital mortality (p=.031) than the other patients.DIC scores were able to predict MODS, and DIC was associated with MODS during the early stage of ARDS. Persistent DIC may also have role in this association.

Patients with tissue injury due to severe trauma are at an increased risk for heparin-induced thrombocytopenia (HIT). However, HIT and its incidence have not been evaluated in patients with extensive burns. We describe two cases of extensive burn injuries with HIT in an attempt to recognize the pathology and clinical significance of HIT in patients with extensive burn injuries.Case 1 was a woman in her 50 s with burn injuries (total burn surface area, 60%). On day 9, her platelet count decreased significantly, and she was positive for the anti-platelet factor-4 immunoglobulin (Ig)-G antibody. On day 22, catheter-related iliac vein thrombosis was diagnosed. Case 2 was a man in his 40 s with burn injuries (total burn surface area, 77%). On day 5, he was diagnosed as having cerebellar infarction. His platelet count decreased significantly, and he was positive for the anti-platelet factor-4 IgG antibody on day 9. His condition was also complicated with pulmonary thrombosis. In both patients, heparin was used only to maintain arterial catheter patency. In conclusion, physicians must consider the possibility of HIT as a cause of thrombocytopenia in patients with burn, and it is necessary to discontinue all heparin and administer non-heparin-anticoagulant when HIT is clinically suspected. Further evaluation of HIT in patients with burn injuries is required. Keywords: Heparin, Thrombosis, Heparin-induced thrombocytopenia antibodies, Extensive burn

Coronavirus disease (COVID-19), an infectious disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese Rapid/Living recommendations on drug management for COVID-19 using the experience of creating the J-SSCG.The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of recommendations. The first edition of this guideline was released on September 9, 2020, and this is the revised edition (version 5.0; released on July 15, 2022). Clinical questions (CQs) were set for the following 10 drugs: favipiravir (CQ1), remdesivir (CQ2), corticosteroids (CQ4), tocilizumab (CQ5), anticoagulants (CQ7), baricitinib (CQ8), casirivimab/imdevimab (CQ9-1), sotrovimab (CQ9-2), molnupiravir (CQ10), and nirmatrelvir/ritonavir (CQ11).Favipiravir is not suggested for all patients with COVID-19 (GRADE 2C). Remdesivir is suggested for patients with mild COVID-19 who do not require oxygen, and patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (both GRADE 2B). Corticosteroids are recommended for moderate and severe COVID-19 (GRADE 1B, 1A). However, their administration is not recommended for mild COVID-19 (GRADE 1B). Tocilizumab is suggested for moderate and severe COVID-19 (GRADE 2B, 2C). Anticoagulant administration is recommended for moderate and severe COVID-19 (Good Practice Statement). Baricitinib is suggested for moderate and severe COVID-19 (both GRADE 2C). Casirivimab/imdevimab and sotrovimab are recommended for mild COVID-19 (both GRADE 2C). Molnupiravir and nirmatrelvir/ritonavir are recommended for mild COVID-19 (both GRADE 2C). SARS-CoV-2 mutant strains emerge occasionally, and each time, the treatment policy at clinics is forced to change drastically. We ask health-care professionals in the field to refer to the recommendations in these guidelines and use these to keep up to date with COVID-19 epidemiological information.

Background: The development of disseminated intravascular coagulation (DIC) in patients with sepsis has been repeatedly confirmed as a factor associated with poor prognosis. Anticoagulant therapy has been expected to improve sepsis patient outcomes, whereas no randomized controlled trials have demonstrated the survival benefit of anticoagulant therapies in non-specific overall sepsis. Patient selection based on the component of “high disease severity” in addition to “sepsis with DIC” has recently been shown to be important in identifying appropriate target for anticoagulant therapy. The aims of this study were to characterize “severe” sepsis DIC patients, and to identify the patient population benefiting from anticoagulant therapy.Methods: We conducted a retrospective sub-analysis of a prospective multicenter study and enrolled 1,178 adult patients with severe sepsis from 59 intensive care units. We examined the association of patient outcomes, including organ dysfunction and in-hospital mortality, with the DIC score and prothrombin time-international normalized ratio (PT-INR), one of the components of the DIC score, using multivariable regression models including the cross-product term between these indicators. Multivariate Cox proportional hazard regression analysis with non-linear restricted cubic spline including a three-way interaction term (anticoagulant therapy × the DIC score × PT-INR) was also performed. Anticoagulant therapy was defined as the administration of antithrombin, recombinant human thrombomodulin, or their combination.Results: The regression model showed that organ dysfunction and in-hospital mortality deteriorated with higher PT-INR values in the range of less than 1.5 and that this trend was more pronounced with higher DIC scores. Three-way interaction analysis demonstrated that anticoagulant therapy was associated with better survival outcome in patients with a high DIC score and high PT-INR. Furthermore, we identified a DIC score ≥ 5 and PT-INR ≥ 1.5 as the clinical threshold for identification of optimal targets for anticoagulant therapy.Conclusions: The combined use of the DIC score and PT-INR, one of the items of the score, helps to select the optimal patient population for anticoagulant therapy in sepsis-induced DIC. Diagnosing DIC with a sensitive DIC scoring system, followed by the identification of the optimal patient population for anticoagulant therapy may be useful for controlling sepsis-induced DIC. Trial registration: UMIN-CTR, UMIN000019588. Registered on November 16, 2015.

There are few assessments of sedatives during the acute phase under sedation protocols for patients with sepsis. We aimed to compare the influence of different sedation strategies using midazolam and propofol under light sedation on clinical outcomes of ventilated patients with sepsis.This study was aThe midazolam and propofol groups consisted of 51 and 66 patients, respectively. Both groups had similar characteristics, except for age and emergency surgery. The number of well-controlled sedation patients in the propofol group on day three was significantly higher than that in the midazolam group (odds ratio [OR] 3.9, 95% CI [1.30, 11.7]). The incidence of daily coma and delirium within the initial week was different between groups and increased with midazolam administration (P = 0.0138). The number of Confusion Assessment Method for ICU-positive patients was significantly higher in the midazolam group than in the propofol group (OR 5.71, 95% CI [2.30, 14.2]).In patients with sepsis required mechanical ventilation, sedation with midazolam based on a light sedation protocol may be associated with inappropriate sedation during the acute phase, with increased coma and delirium as compared to propofol.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health concern in 2021. However, the risk of attending schools during the pandemic remains unevaluated. This study estimated the secondary transmission rate at schools using the results of a real-time reverse transcription-polymerase chain reaction (RT-PCR) screening test performed between July 2020 and April 2021, before starting the nationwide mass vaccination. A total of 1,924 students (20 RT-PCR-positive; 1.0%) from 52 schools or preschools were evaluated, together with 1,379 non-adults (95 RT-PCR-positive; 6.9%) exposed to SARS-CoV-2 in non-school environments. Assuming that the infectious index cases were asymptomatic and the transmission at schools followed a Bernoulli process, we estimated the probability of transmission after each contact at school as approximately 0.005 (0.5% per contact) with the current infection prevention measures at schools in Japan (i.e., hand hygiene, physical distancing, wearing masks, and effective ventilation). Furthermore, assuming that all children are capable of carrying the infection, then contact between an index case and 20-30 students per day at schools would yield the expected value for secondary cases of ≥ 1.0, during the 10 days of the infectious period. In conclusion, with the current infection prevention measures at schools in Japan, secondary transmission at schools would occur in approximately every 200 contacts. When considering this rate, compliance with the current infection prevention measures at schools and early detection and quarantine of the index cases would be effective in preventing the spread of COVID-19 at schools.

Background The coronavirus disease 2019 (COVID‐19) has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J‐SSCG) 2020 Special Committee created the Japanese rapid/living recommendations on drug management for COVID‐19 using the experience of creating the J‐SSCG. Methods The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of the recommendations. The first edition of this guideline was released on September 9, 2020, and this document is the revised edition (version 4.0; released on September 9, 2021). Clinical questions (CQs) were set for the following seven drugs: favipiravir (CQ1), remdesivir (CQ2), corticosteroids (CQ4), tocilizumab (CQ5), anticoagulants (CQ7), baricitinib (CQ8), and casirivimab/imdevimab (CQ9). Two CQs (hydroxychloroquine [CQ3] and ciclesonide [CQ6]) were retrieved in this updated version. Recommendations Favipiravir is not suggested for all patients with COVID‐19 (GRADE 2C). Remdesivir is suggested for patients with moderate COVID‐19 requiring supplemental oxygen/hospitalization (GRADE 2B). Corticosteroids are recommended for patients with moderate COVID‐19 requiring supplemental oxygen/hospitalization (GRADE 1B) and for patients with severe COVID‐19 requiring mechanical ventilation/intensive care (GRADE 1A); however, their administration is not recommended for patients with mild COVID‐19 not requiring supplemental oxygen (GRADE 1B). Tocilizumab is suggested for patients with moderate COVID‐19 requiring supplemental oxygen/hospitalization (GRADE 2B). Anticoagulant administration is recommended for patients with moderate COVID‐19 requiring supplemental oxygen/hospitalization and patients with severe COVID‐19 requiring mechanical ventilation/intensive care (good practice statement). Baricitinib is suggested for patients with moderate COVID‐19 requiring supplemental oxygen/hospitalization (GRADE 2C). Casirivimab/imdevimab is recommended for patients with mild COVID‐19 not requiring supplemental oxygen (GRADE 1B). We hope that these updated clinical practice guidelines will help medical professionals involved in the care of patients with COVID‐19., The Japanese rapid/living recommendations on drug management for coronavirus disease 2019 (COVID‐19) were released on September 9, 2020, as the first edition. Here, we present the revised edition (version 4.0; released on September 9, 2021).

The main objectives of critical care of severe traumatic brain injury(TBI)are the prevention and treatment of intracranial hypertension and secondary brain insults, preservation of cerebral perfusion pressure, and optimization of cerebral oxygenation. The critical care management of severe TBI will be discussed with a focus on the monitoring and avoidance or minimization of secondary brain insults, with emphasis on understanding the underlying physiology and pathophysiology. The evolution of critical care of severe traumatic brain injury will also be discussed along with the accumulating knowledge and experience.

Background: Hepatic compartment syndrome (HCS) is a complication of nonoperative management in patients with blunt hepatic injury. Although decompression of elevated intrahepatic pressure through surgical exploration or drainage and hemorrhage control are required to manage this condition, evidence for such a management for this complication is insufficient. Herein, we report a pediatric patient treated with a planned combination strategy of surgical decompression with perihepatic packing to reduce intrahepatic pressure and subcapsular hemorrhage control as well as angioembolization to control intraparenchymal hemorrhage. Case presentation: A 12-year-old boy was referred to our emergency department 5 h after sustaining severe bruising in the upper abdomen in a traffic accident. Computed tomography (CT) showed an intraparenchymal hematoma in the right lobe of the liver; nonoperative management was selected based on stable hemodynamic status. Two days after the injury, he complained of severe abdominal pain and shock. CT showed an intraparenchymal and large subcapsular hematoma with right branch compression of the portal vein and extravasation of contrast material. Laboratory data showed progression of hepatocellular damage. We successfully managed this patient with a planned combination strategy of surgical decompression with perihepatic packing for reduction of intrahepatic pressure and subcapsular hemorrhage control, followed by angioembolization for control of intraparenchymal hemorrhage. Conclusion: Our study suggests that for the management of HCS, a planned combination strategy of damage control surgery and angioembolization is a therapeutic option.

Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, and their combination. The multivariate Cox proportional hazard regression model showed that the risk increases were suppressed in the high-DIC-score patients aged 60–70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk in patients aged 50–60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60–70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis.

Background Sepsis is associated with life-threatening organ dysfunction caused by a dysregulated host response to infection. However, no specific therapy has been shown to improve mortality in patients with sepsis. We conducted a study to clarify the utilization status of various BPTs and the clinical characteristics of patients who received BPTs in northern Japan. In addition, the association of various BPTs with clinical outcomes was examined. Methods This is a sub-analysis of the Tohoku Sepsis Registry, a multicenter, prospective, observational cohort study. To determine whether BPT was independently associated with in-hospital mortality in patients with severe sepsis, the following analyses were performed. Differences between survivors and non-survivors were assessed using Wilcoxon rank sum tests for continuous variables and Chi-square tests for categorical variables. Univariate logistic regression analysis was used to evaluate the factors associated with in-hospital mortality. In the multivariate logistic regression analysis, adjustments were made for the variables that were significant in the univariate logistic regression analysis. Clinical factors associated with mortality were analyzed. Results We enrolled 616 consecutive patients (≥ 18 years) with median Sequential Organ Failure Assessment scores of 8.0. During median of 22 days hospitalization, 139 patients died (mortality 22.6%). 20.7% of patients with severe sepsis received any type of BPT (mortality 38.6%). BPT consisted of 65.1% continuous renal replacement therapy (CRRT) with renal indication (mortality 48.8%), 26.0% CRRT with non-renal indication (mortality 21.2%), 22.2% intermittent renal replacement therapy (mortality 32.1%), and 33.1% polymyxin B-immobilized fiber column-direct hemoperfusion (mortality 42.9%). Meanwhile, no BPT group (mortality 18.5%) showed a significantly lower mortality than any BPT group. Besides, in multivariate analyses, all BPT modes were not independently associated with all-cause mortality. Conclusions This study suggested the clinical status of BPTs for severe sepsis patients in northern Japan. Among all types of BPT, continuous renal replacement therapy (CRRT) for renal indication was most frequently selected. Severe sepsis patients received BPT had a higher mortality and severity; however, the BPT implementation may not be associated with mortality. Trial registration UMIN-CTR, UMIN000010297, Registered on 22 March 2013, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012055).

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

We assessed the influence of admission hypoglycemia on mortality in sepsis patients according to body mass index (BMI). We included 1,184 patients (age ≥ 16 years) with severe sepsis diagnosed using Sepsis-2 criteria. The outcome was in-hospital mortality. Using multivariate logistic regression, we examined the association between hypoglycemia and in-hospital mortality. Overall, 1,103 patients were analyzed. Patients were divided into groups according to the initial blood glucose level, i.e., 2. Hypoglycemia was noted in 65 patients, with low (n = 13), normal (n = 38), and high BMI (n = 14). Hypoglycemia patients showed higher in-hospital mortality than those without in the normal BMI group but not in the low and high BMI groups. In multivariate logistic regression, hypoglycemia was non-significantly associated with higher mortality in all patients (p = 0.268). However, there was a significant interaction between normal BMI patients and hypoglycemia on in-hospital mortality but not between low or high BMI patients and hypoglycemia (p = 0.0476). Hypoglycemia at admission in sepsis patients was associated with high mortality in normal BMI patients but not in low or high BMI patients. This association may be used as a prognostic marker in sepsis patients.

Background: Hypoglycaemia at admission is associated with high mortality in sepsis patients. The association of hypoglycaemia and body mass index (BMI) with mortality in sepsis patients has not been clarified. We aimed to assess the influence hypoglycaemia at admission on mortality in sepsis patients according to BMI categories.Methods: This was a secondary analysis of a multicentre, prospective cohort study of 59 intensive care unit in Japan. The study included 1,184 patients (age ≥16 years) with severe sepsis; the diagnosis was made based on the Sepsis-2 criteria. After excluding patients with missing data of glucose level, BMI, or survival at discharge, patients were divided into groups according to the initial blood glucose level, 2. The main outcome measure was in-hospital mortality. A multivariate logistic regression model was used to examine the association between hypoglycaemia and in-hospital mortality. BMI category-by-hypoglycaemia interactions were evaluated to assess the heterogeneity of the impact of hypoglycaemia on in-hospital mortality across BMI categories.Results: In total, 1,103 patients, including 65 patients with hypoglycaemia, were analysed. Among patients with hypoglycaemia, 13 had low, 38 had normal, and 14 had high BMI. Patients with hypoglycaemia showed higher in-hospital mortality (18/38, 47.4%) than those without hypoglycaemia (119/584, 20.4%) in the normal BMI group but not in the low and high BMI groups. In the multivariate logistic regression model, hypoglycaemia was not significantly associated with higher mortality in all patients (odds ratio [OR] 1.41; 95% confidence interval [CI] 0.77–2.58). However, there was a significant interaction between patients with normal BMI and hypoglycaemia on in-hospital mortality but not between patients with low or high BMI and hypoglycaemia (OR 2.32, 95% CI 1.05–5.07), and p for interaction: 0.0476).Conclusions: Hypoglycaemia at admission in sepsis patients was associated with high mortality in patients with normal BMI, but not in those with low or high BMI. This association may be used as a prognostic marker in sepsis patients.

Background: Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This study aimed to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis in accordance with the DIC diagnostic criteria.Methods: We conducted a retrospective sub-analysis of a prospective multicenter study. Fifty-nine intensive care units in Japan, from January 2016 to March 2017 were included. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into two groups as follows: anticoagulant group; patients who received anticoagulant therapy, and non-anticoagulant group; patients who did not receive anticoagulant therapy. Patients in anticoagulant therapy group were administered antithrombin, recombinant human thrombomodulin and their combination.Results: The multivariate Cox proportional hazard regression model including a three-way interaction term among anticoagulant therapy, DIC score and age showed that the increases in the risk were suppressed in patients receiving anticoagulant therapy in patients aged 60 to 70 years with high DIC scores. For patients aged 50 years, the risk in the non-anticoagulant group tended to increase concomitantly with increases in the DIC score in the low score range, while there was no increase in the risk in the high score range and favorable association of anti-coagulant therapy on hospital mortality was not found. In patients aged 80 years, the non-anticoagulant group indicated a certain risk regardless of the DIC score and the anti-coagulant therapy showed no beneficial effect on the decrease in risk of hospital mortality. Furthermore, anticoagulant therapy in the lower DIC score range increased the risk in patients aged 50 to 60 years.Conclusions: Anticoagulant therapy, the administration of antithrombin, recombinant human thrombomodulin, and their combination, were associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60 to 70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older septic patients.Trial registration: UMIN-CTR, UMIN000019588. Registered on 16 November 2015.

Purpose: To elucidate whether fluid balance and body weight change are associated with failed planned extubation. Materials and Methods: Patients who received invasive mechanical ventilation for over 24 hours were enrolled and divided into extubation success and extubation failure groups. Fluid balance and body weight fluctuation within 24 and 48 hours before extubation and from admission to planned extubation were calculated. The primary outcome was extubation failure (ie, all-cause reintubation within 72 hours). The association of extubation failure with fluid balance and body weight change was assessed via logistic regression analysis. Results: Extubation failure occurred in 12(7.4%)/161 patients. The extubation success group had a significantly lower fluid balance within 24 hours before extubation than did the extubation failure group (−276 mL [−1111 to 456] vs 1217 mL [503 to 1875], P = .002). However, fluid balance within 48 hours before extubation, cumulative fluid balance, and body weight change were not significantly different between the 2 groups. The sensitivity and specificity of water balance +1000 mL within 24 hours before extubation for the extubation failure group were 0.54 and 0.84, respectively, based on the receiver operating characteristic curve. Logistic regression analysis showed that fluid balance within 24 hours before extubation was associated with extubation failure (odds ratio: 22.9, 95% confidence interval: 4.1-128.4). Conclusions: A larger fluid balance within 24 hours before extubation is associated with extubation failure. Thus, fluid balance may be a good indicator of extubation outcome.

Objective To identify the outcome of patients with sepsis using high-frequency blood pressure data. Materials and methods This retrospective observational study was conducted at a university hospital ICU (derivation study) and at two urban hospitals (validation study) with data from adult sepsis patients who visited the centers during the same period. The area under the curve (AUC) of blood pressure falling below threshold was calculated. The predictive 90-day mortality (primary endpoint) area under threshold (AUT) and critical blood pressure were calculated as the maximum area under the curve of the receiver operating characteristic curve (AUCROC) and the threshold minus average AUT (derivation study), respectively. For the validation study, the derived 90-day mortality AUCROC (using critical blood pressure) was compared with Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II, and APACHE III. Results Derivation cohort (N = 137): the drop area from the mean blood pressure of 70 mmHg at 24-48 hours most accurately predicted 90-day mortality [critical blood pressure, 67.8 mmHg; AUCROC, 0.763; 95% confidence interval (CI), 0.653-0.890]. Validation cohort (N = 141): the 90-day mortality AUCROC (0.776) compared with the AUCROC for SOFA (0.711), SAPSII (0.771), APACHE II (0.745), and APACHE III (0.710) was not significantly different from the critical blood pressure 67.8 mmHg (P = 0.420). Conclusion High-frequency arterial blood pressure data of the period and extent of blood pressure depression can be useful in predicting the clinical outcomes of patients with sepsis.

Background Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two components for the effectiveness of therapy remain unknown. Objective This article identifies the optimal target of anticoagulant therapy in sepsis. Methods We used a prospective nationwide cohort targeting consecutive adult severe sepsis patients in 59 intensive care units in Japan to assess associations between anticoagulant therapy and in-hospital mortality according to DIC (International Society on Thrombosis and Haemostasis [ISTH] overt and Japanese Association for Acute Medicine DIC scores) and disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment scores). Multivariable Cox proportional hazard regression analysis with nonlinear restricted cubic spline including a two-way interaction term (treatment × each score) and three-way interaction term (treatment × ISTH overt DIC score × APACHE II score) was performed. Results The final study cohort comprised 1,178 sepsis patients (371 received anticoagulants and 768 did not). The regression model including the two-way interaction term showed significant interaction between intervention and disease severity as indicated by the ISTH overt DIC score and APACHE II score (p = 0.046 and p = 0.101, respectively). Three-way interaction analysis revealed that risk hazard was suppressed in the anticoagulant group compared with the control group in the most severe subset of both scores. Conclusion Anticoagulant therapy was associated with better outcome according to the deterioration of both DIC and disease severity, suggesting that anticoagulant therapy should be restricted to patients having DIC and high disease severity simultaneously.

Purpose Hospital services are reduced during off-hour such as nighttime or weekend. Investigations of the off-hour effect on initial management and outcomes in sepsis are very limited. Thus, we tested the hypothesis that patients who were diagnosed with severe sepsis during the nighttime or on non-business days had altered initial management and clinical outcomes. Materials and methods Patients with severe sepsis from 59 ICUs between 2016 and 2017 were enrolled. The patients were categorized according to the diagnosis time or day and were then compared. The primary outcome was in-hospital mortality. Results One thousand one hundred and forty-eight patients were analyzed; 769 daytime patients, vs. 379 nighttime patients, and 791 business day patients vs. 357 non-business day patients. There were no significant differences in in-hospital mortality between either daytime and nighttime (24.4% vs. 21.4%, P = .27; nighttime, adjusted odds ratio [OR] 1.17, 95% confidence interval [CI], 0.87–1.59, P = .30) or between business and non-business days (22.9% vs. 24.6%, P = .55; non-business day, adjusted OR 0.85, 95% CI 0.60–1.22, P = .85). Time to antibiotics was significantly shorter in the nighttime (114 vs. 89 min, P = .0055). Conclusions Nighttime and weekends were not associated with increased in-hospital mortality of severe sepsis.

To investigate the impact of body temperature on disease severity, implementation of sepsis bundles, and outcomes in severe sepsis patients.Retrospective sub-analysis.Fifty-nine ICUs in Japan, from January 2016 to March 2017.Adult patients with severe sepsis based on Sepsis-2 were enrolled and divided into three categories (body temperature36°C, 36-38°C,38°C), using the core body temperature at ICU admission.None.Compliance with the bundles proposed in the Surviving Sepsis Campaign Guidelines 2012, in-hospital mortality, disposition after discharge, and the number of ICU and ventilator-free days were evaluated. Of 1,143 enrolled patients, 127, 565, and 451 were categorized as having body temperature less than 36°C, 36-38°C, and greater than 38°C, respectively. Hypothermia-body temperature less than 36°C-was observed in 11.1% of patients. Patients with hypothermia were significantly older than those with a body temperature of 36-38°C or greater than 38°C and had a lower body mass index and higher prevalence of septic shock than those with body temperature greater than 38°C. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on the day of enrollment were also significantly higher in hypothermia patients. Implementation rates of the entire 3-hour bundle and administration of broad-spectrum antibiotics significantly differed across categories; implementation rates were significantly lower in patients with body temperature less than 36°C than in those with body temperature greater than 38°C. Implementation rate of the entire 3-hour resuscitation bundle + vasopressor use + remeasured lactate significantly differed across categories, as did the in-hospital and 28-day mortality. The odds ratio for in-hospital mortality relative to the reference range of body temperature greater than 38°C was 1.760 (95% CI, 1.134-2.732) in the group with hypothermia. The proportions of ICU-free and ventilator-free days also significantly differed between categories and were significantly smaller in patients with hypothermia.Hypothermia was associated with a significantly higher disease severity, mortality risk, and lower implementation of sepsis bundles.