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Abstract Background In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time and outcomes in accidental hypothermia (AH) patients compared to those of patients without AH has not been fully investigated. Methods This was a secondary analysis of the retrospective multicenter registry in Japan. We enrolled patients aged ≥ 18 years who had been admitted to the emergency department for OHCA and had undergone ECPR between January, 2013 and December, 2018. AH was defined as an arrival body temperature below 32 °C. The primary outcome was survival to discharge. Cubic spline analyses were performed to assess the non-linear associations between low-flow time and outcomes stratified by the presence of AH. We also analyzed the interaction between low-flow time and the presence of AH. Results Of 1252 eligible patients, 105 (8.4%) and 1147 (91.6%) were in the AH and non-AH groups, respectively. Median low-flow time was 60 (47–79) min in the AH group and 51 (42–62) min in the non-AH group. The survival discharge rates in the AH and non-AH groups were 44.8% and 25.4%, respectively. The cubic spline analyses showed that survival discharge rate remained constant regardless of low-flow time in the AH group. Conversely, a decreasing trend was identified in the survival discharge rate with longer low-flow time in the non-AH group. The interaction analysis revealed a significant interaction between low-flow time and AH in survival discharge rate (p for interaction = 0.048). Conclusions OHCA patients with arrival body temperature

Abstract Background Patients who receive invasive mechanical ventilation (IMV) in the intensive care unit (ICU) have exhibited lower in-hospital mortality rates than those who are treated outside. However, the patient-, hospital-, and regional factors influencing the ICU admission of patients with IMV have not been quantitatively examined. Methods This retrospective cohort study used data from the nationwide Japanese inpatient administrative database and medical facility statistics. We included patients aged ≥ 15 years who underwent IMV between April 2018 and March 2019. The primary outcome was ICU admission on the day of IMV initiation. Multilevel logistic regression analyses incorporating patient-, hospital-, or regional-level variables were used to assess cluster effects by calculating the intraclass correlation coefficient (ICC), median odds ratio (MOR), and proportional change in variance (PCV). Results Among 83,346 eligible patients from 546 hospitals across 140 areas, 40.4% were treated in ICUs on their IMV start day. ICU admission rates varied widely between hospitals (median 0.7%, interquartile range 0–44.5%) and regions (median 28.7%, interquartile range 0.9–46.2%). Multilevel analyses revealed significant effects of hospital cluster (ICC 82.2% and MOR 41.4) and regional cluster (ICC 67.3% and MOR 12.0). Including patient-level variables did not change these ICCs and MORs, with a PCV of 2.3% and − 1.0%, respectively. Further adjustment for hospital- and regional-level variables decreased the ICC and MOR, with a PCV of 95.2% and 85.6%, respectively. Among the hospital- and regional-level variables, hospitals with ICU beds and regions with ICU beds had a statistically significant and strong association with ICU admission. Conclusions Our results revealed that primarily hospital and regional factors, rather than patient-related ones, opposed ICU admissions for patients with IMV. This has important implications for healthcare policymakers planning interventions for optimal ICU resource allocation.

Abstract Introduction Limited data are available regarding the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) in patients experiencing major hemorrhage or requiring expeditious surgical intervention, both globally and within Japan. Methods We executed a prospective, observational post-marketing surveillance study of patients receiving 4F-PCC for the first time between September 19, 2017 and August 15, 2018 in Japan. Patients were subjected to a comprehensive follow-up for a duration of 4 weeks. Results Of 1381 eligible patients, 1271 (92%) received a vitamin K antagonist. Among these, 58% were aged ≥ 75 years, 49% manifested atrial fibrillation, 17% presented with valvular heart disease, and 6% exhibited venous thromboembolism. The median (range) international normalized ratio was 2.67 (0.96–27.11) at baseline and 1.21 (0.45–6.61) at first measurement post-administration of 4F-PCC. The most common reason for 4F-PCC administration was intracranial hemorrhage (59.6%), followed by gastrointestinal bleeding (6.6%). Hemostatic effectiveness was achieved in 85.8% of patients. The incidences of adverse drug reactions (ADRs) and serious ADRs were 3.9% and 2.8%, respectively. Thromboembolic events (TEEs) occurred in 20 (1.5%) patients, with a mean onset of 10 days. The majority of TEEs were classified as nervous system disorders (55%). At the time of TEE, only 13% of patients resumed anticoagulant therapy. Conclusion The incidence of TEEs following treatment with 4F-PCC did not surpass those observed in phase 3 trials. No novel safety signals were identified. The safety and effectiveness of 4F-PCC in Japanese real-world practice were in harmony with the observations of prior studies.

Abstract Background The appropriateness of a restrictive transfusion strategy for those with active bleeding after traumatic injury remains uncertain. Given the association between tissue hypoxia and lactate levels, we hypothesized that the optimal transfusion strategy may differ based on lactate levels. This post hoc analysis of the RESTRIC trial sought to investigate the association between transfusion strategies and patient outcomes based on initial lactate levels. Methods We performed a post hoc analysis of the RESTRIC trial, a cluster-randomized, crossover, non-inferiority multicenter trials, comparing a restrictive and liberal red blood cell transfusion strategy for adult trauma patients at risk of major bleeding. This was conducted during the initial phase of trauma resuscitation; from emergency department arrival up to 7 days after hospital admission or intensive care unit (ICU) discharge. Patients were grouped by lactate levels at emergency department arrival: low (

Abstract Background Coronavirus disease 2019 (COVID-19) has exposed critical care supply shortages worldwide. This study aimed to investigate the association between regional critical care capacity and the incidence of invasive mechanical ventilation following novel COVID-19 during the pandemic in Japan, a country with a limited intensive care unit (ICU) bed capacity of a median of 5.1 ICU beds per 100,000 individuals. Methods This population-based cohort study used data from the CRoss Icu Searchable Information System database and publicly available databases provided by the Japanese government and Japanese Society of Intensive Care Medicine. We identified patients recently diagnosed with COVID-19, those who received invasive mechanical ventilation, and those who received extracorporeal membrane oxygenation (ECMO) between February 2020 and March 2023. We analyzed the association between regional critical care capacity (ICU beds, high-dependency care unit (HDU) beds, resource-rich ICU beds, and intensivists) and the incidence of invasive mechanical ventilation, ECMO, and risk-adjusted mortality across 47 Japanese prefectures. Results Among the approximately 127 million individuals residing in Japan, 33,189,809 were recently diagnosed with COVID-19, with 12,203 and 1,426 COVID-19 patients on invasive mechanical ventilation and ECMO, respectively, during the study period. Prefecture-level linear regression analysis revealed that the addition of ICU beds, resource-rich ICU beds, and intensivists per 100,000 individuals increased the incidence of IMV by 5.37 (95% confidence interval, 1.99–8.76), 7.27 (1.61–12.9), and 13.12 (3.48–22.76), respectively. However, the number of HDU beds per 100,000 individuals was not statistically significantly associated with the incidence of invasive mechanical ventilation. None of the four indicators of regional critical care capacity was statistically significantly associated with the incidence of ECMO and risk-adjusted mortality. Conclusions The results of prefecture-level analyses demonstrate that increased numbers of ICU beds, resource-rich ICU beds, and intensivists are associated with the incidence of invasive mechanical ventilation among patients recently diagnosed with COVID-19 during the pandemic. These findings have important implications for healthcare policymakers, aiding in efficiently allocating critical care resources during crises, particularly in regions with limited ICU bed capacities. Registry and the registration no. of the study/trial The approval date of the registry was August 20, 2020, and the registration no. of the study was lUMIN000041450.

Background: Hybrid emergency department (ED), which are equipped with fluoroscopy and computed tomography has been developed in Japan as a novel emergency care room. Although hybrid ED is effective in improving the outcomes of severe trauma, its influence on the management of out-of-hospital cardiac arrest (OHCA) requiring extracorporeal cardiopulmonary resuscitation (ECPR) remains unclear. Objectives: The aim of this study was to elucidate the impact of hybrid ED on ECPR procedures and outcome in OHCA patients focusing on time from hospital arrival to establishment of ECPR. Methods: A retrospective single-center cohort study was conducted, including adult OHCA patients who underwent ECPR between April 2013 and March 2022. Patients treated in conventional ED were compared with those in hybrid ED. Primary outcome was time from hospital arrival to ECPR initiation. Secondary outcomes included favorable neurological outcome at 30 days and incidence of cannulation-related adverse events. Results: Hybrid ED installation led to a significant decrease in time to ECPR initiation. In the interpreted time series analysis for the time from hospital arrival to establishment ECPR, there was statistically significant upward level change and downward trend change after the installation of hybrid ED. These results mean the time from hospital arrival to the establishment of ECPR was prolonged just after installation of hybrid ER, and the time from hospital arrival to the establishment of ECPR was shortened over time. There were no statistically significant differences between the conventional and hybrid ED groups on the favorable neurological outcome and cannulation-related adverse events. Conclusions: The installation of hybrid ED was associated with shortened time from hospital arrival to establishment of ECPR. Further evaluation is needed to elucidate the effects of hybrid ED on OHCA and determine an optimal strategy.

Abstract Background Previous studies have reported conflicting results regarding fresh frozen plasma (FFP)-to-red blood cell (RBC) ratio and platelet-to-RBC ratio on outcomes for massive transfusion for trauma. Moreover, nationwide data on massive transfusion practices for trauma in the real-world clinical setting are scarce. This study aimed to examine the nationwide practice patterns and trends in massive transfusion for trauma in Japan using a national administrative, inpatient database. Method We identified patients who underwent emergency hospitalization for trauma and received massive transfusion, defined as administration of at least 20 units of RBC within the first 2 days of admission, using the nationwide inpatient database, which covers approximately 90% of all tertiary emergency hospitals in Japan, between 2011 and 2020. Trends in the incidence and practice patterns of massive transfusion were described by calendar year. The association of practice patterns with mortality or adverse events was tested. Results A total of 3,530,846 trauma hospitalizations were identified, of which 5247 (0.15%) received massive transfusion. A significant declining trend was observed in the incidence of massive transfusion in trauma hospitalizations from 0.24% in 2011 to 0.10% in 2020 (P for trend

Abstract Background The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. Methods This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7–9 or 10–12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. Results The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49–2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. Conclusions Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. Trial registration number: umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.

Abstract Background Polymyxin B hemadsorption (PMX-HA) reduces blood endotoxin levels, but characteristics of patients with sepsis likely to benefit from PMX-HA are not well known. We sought to identify patient subgroups likely to benefit from PMX-HA. Methods We retrospectively identified 1911 patients with sepsis from a retrospective observational study in Japan (the JSEPTIC-DIC study) and 286 patients with endotoxemic septic shock from a randomized controlled trial in North America that restricted patients to those with high endotoxin activity (the EUPHRATES trial). We applied the machine learning-based causal forest model to the JSEPTIC-DIC cohort to investigate heterogeneity in treatment effects of PMX-HA on 28-day survival after adjusting for potential confounders and ascertain the best criteria for PMX-HA use. The derived criteria for targeted therapy by PMX-HA were validated using the EUPHRATES trial cohort. Results The causal forest model revealed heterogeneity in treatment effects of PMX-HA. Since patients having higher treatment effects were more likely to have severe coagulopathy and hyperlactatemia, we identified the potential treatment targets of PMX-HA as patients with PT-INR > 1.4 or lactate > 3 mmol/L. In the EUPHRATES trial cohort, PMX-HA use on the targeted subpopulation (75% of all patients) was significantly associated with higher 28-day survival (PMX-HA vs. control, 68% vs. 52%; treatment effect of PMX-HA, + 16% [95% CI + 2.2% to + 30%], p = 0.02). Conclusions Abnormal coagulation and hyperlactatemia in septic patients with high endotoxin activity appear to be helpful to identify patients who may benefit most from PMX-HA. Our findings will inform enrollment criteria for future interventional trials targeting patients with coagulopathy and hyperlactatemia.

BackgroundTrauma-induced coagulopathy (TIC) is a common and potentially life-threatening coagulopathy as a result of traumatic injury, characterized by abnormal blood clotting and bleeding. Although several treatments have been proposed for TIC, their effectiveness and safety remain unclear. Further, numerous systematic reviews and meta-analyses on trauma have been conducted; however, to our knowledge, there is no systematic review and meta-analysis that specifically focuses on TIC management. Therefore, a comprehensive synthesis of the available evidence on interventions for TIC is needed. ObjectiveThis systematic review and meta-analysis aim to evaluate the effectiveness and safety of interventions for the management of TIC. MethodsWe will conduct a systematic review and meta-analysis of randomized and nonrandomized controlled trials as well as observational studies regarding severe trauma in patients with TIC. The interventions will include administration of coagulation factor concentrates, tranexamic acid, and blood component products. The control group will be managed with an ordinal transfusion or administered placebo. The primary outcome will be in-hospital mortality. We will search the electronic databases of MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. Two reviewers will independently screen the titles and abstracts, retrieve the full text of the selected articles, and extract essential data. We will apply uniform criteria for evaluating the risk of bias associated with individual randomized controlled trials and nonrandomized trials based on the Cochrane risk-of-bias tool. Risk ratio values will be expressed as point estimates with 95% CIs. Continuous variables will be expressed as the mean difference along with their 95% CIs and P values. We will assess the strength of evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. This review will be the first systematic review and meta-analysis providing information on the effectiveness and safety of interventions for the management of TIC, including the administration of coagulation factor concentrates, tranexamic acid, and blood component products. Ethics approval and patient consent were not required for this study protocol, as we conducted a systematic review and meta-analysis of publicly available data, without any direct involvement of human participants. ResultsWe will summarize the selection of the eligible studies using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. The results will be presented in a table summarizing the evidence. The results of the meta-analysis will be depicted using figures and forest plots. ConclusionsThis systematic review will provide updated information on the efficacy and safety of using coagulation factor concentrates, tranexamic acid, and blood component products for patients with TIC. To our knowledge, there is no systematic review and meta-analysis that specifically focuses on treatments for TIC. Trial RegistrationUMIN registry UMIN000050170; https://tinyurl.com/yr8pcrj6 International Registered Report Identifier (IRRID)DERR1-10.2196/49582

Abstract 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 proved important in identifying appropriate targets 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 This retrospective sub-analysis of a prospective multicenter study included 1,178 adult patients with severe sepsis from 59 intensive care units in Japan from January 2016 to March 2017. 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 In total, we analyzed 1013 patients. The regression model showed that organ dysfunction and in-hospital mortality deteriorated with higher PT-INR values in the range of

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.

Abstract Background 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. Methods 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. Results 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

Abstract 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 the best of 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, 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 from 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.

Abstract 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.

Abstract 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%.

Abstract 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.

Abstract 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.

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.

Abstract Aim Multisystem inflammatory syndrome in adults (MIS‐A) is a hyperinflammatory multisystem condition associated with coronavirus disease (COVID‐19). Critically ill COVID‐19 patients may develop multiorgan damage and elevated inflammatory responses, thus making it difficult to differentiate between progression to organ damage due to COVID‐19 itself or MIS‐A. This study aimed to explore the characteristics and complications of MIS‐A in critical COVID‐19 patients. Methods The Japan Extracorporeal Membrane Oxygenation (ECMO) Network and ICU Collaboration Network developed a web‐based database system called the CRoss Intensive Care Unit Searchable Information System (CRISIS) to monitor critical COVID‐19 patients throughout Japan. We retrospectively identified patients with MIS‐A among critical COVID‐19 patients enrolled from March 2020 to December 2021, using CRISIS. Our MIS‐A definition required patients to be at least 18 years of age, have laboratory evidence of inflammation, severe dysfunction of at least two extrapulmonary organ systems, and no plausible alternative diagnoses. Results Of the 1052 patients, 26 (2.5%) were diagnosed with MIS‐A. The MIS‐A patients had a higher likelihood of using ECMO (13% vs. 46%, p

Abstract Aim Hypoglycemia at admission is associated with high mortality in sepsis patients. However, the influence of body mass index (BMI) on this association remains unknown. Therefore, this study assesses the association of hypoglycemia at admission with mortality in patients with sepsis according to BMI. Methods This was a secondary analysis of a multicenter, prospective cohort study of 59 intensive care units in Japan. We included 1184 patients (age ≥16 years) with severe sepsis and excluded those with missing data on glucose level, BMI, or survival at discharge. The initial blood glucose level of

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.

IntroductionTrauma activates the innate immune system to modulate hemostasis and minimize the damage caused by physiological bodily responses, including the activation of coagulation. Sufficiently severe trauma overwhelms physiological responses and elicits the systemic inflammatory response syndrome, which leads to the onset of disseminated intravascular coagulation (DIC), characterized by dysregulated inflammatory coagulofibrinolytic responses. Impaired anticoagulant mechanisms, including antithrombin, constitutes the pathology of DIC, while the dynamics of antithrombin and relevance to outcomes in trauma-induced coagulopathy have not been fully elucidated. This study investigated the associations of antithrombin activity with DIC onset and outcomes in severely injured patients.MethodsThis retrospective sub-analysis of a multicenter, prospective study included patients with an injury severity score ≥16. We characterized trauma patients with low antithrombin activity (antithrombin 85%). Antithrombin activity at 3 h showed good predictive performance for in-hospital mortality, and a multivariable Cox proportional-hazard regression model with a cross-product term between the antithrombin and DIC showed that the in-hospital mortality in patients with DIC increased with decreased antithrombin activity. A multivariable logistic regression model showed that the odds for the development of MODS in patients with DIC increased with lower antithrombin values.ConclusionDecreased antithrombin activity in trauma-induced coagulopathy is associated with poor outcomes through worsening of DIC.

Aim: 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). Methods: 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). Results: 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%, P

Abstract 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 ).

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 The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the world’s largest public health concern. This study evaluated COVID-19 transmission risks in people in group living environments. A total of 4550 individuals with a history of recent contact with patients at different places (dormitory/home/outside the residences) and levels (close/lower-risk) were tested for SARS-CoV-2 viral RNA using a nasopharyngeal swab test between July 2020 and May 2021. The test-positive rate was highest in individuals who had contact in dormitories (27.5%), but the rates were largely different between dormitories with different infrastructural or lifestyle features and infection control measures among residents. With appropriate infection control measures, the secondary transmission risk in dormitories was adequately suppressed. The household transmission rate (12.6%) was as high as that of close contact outside the residences (11.3%) and accounted for > 60% of the current rate of COVID-19 transmission among non-adults. Household transmission rates synchronized to local epidemics with changed local capacity of quarantining infectious patients. In conclusion, a group living environment is a significant risk factor of secondary transmission. Appropriate infection control measures and quarantine of infectious residents will decrease the risk of secondary transmission in group living environments.

Abstract Trauma patients die from massive bleeding due to disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype in the early phase, which transforms to DIC with a thrombotic phenotype in the late phase of trauma, contributing to the development of multiple organ dysfunction syndrome (MODS) and a consequently poor outcome. This is a sub-analysis of a multicenter prospective descriptive cross-sectional study on DIC to evaluate the effect of a DIC diagnosis on the survival probability and predictive performance of DIC scores for massive transfusion, MODS, and hospital death in severely injured trauma patients. A DIC diagnosis on admission was associated with a lower survival probability (Log Rank P

Abstract Background Information on hyperoxemia among patients with trauma has been limited, other than traumatic brain injuries. This study aimed to elucidate whether hyperoxemia during resuscitation of patients with trauma was associated with unfavorable outcomes. Methods A post hoc analysis of a prospective observational study was carried out at 39 tertiary hospitals in 2016–2018 in adult patients with trauma and injury severity score (ISS) of > 15. Hyperoxemia during resuscitation was defined as PaO2 of ≥ 300 mmHg on hospital arrival and/or 3 h after arrival. Intensive care unit (ICU)-free days were compared between patients with and without hyperoxemia. An inverse probability of treatment weighting (IPW) analysis was conducted to adjust patient characteristics including age, injury mechanism, comorbidities, vital signs on presentation, chest injury severity, and ISS. Analyses were stratified with intubation status at the emergency department (ED). The association between biomarkers and ICU length of stay were then analyzed with multivariate models. Results Among 295 severely injured trauma patients registered, 240 were eligible for analysis. Patients in the hyperoxemia group (n = 58) had shorter ICU-free days than those in the non-hyperoxemia group [17 (10–21) vs 23 (16–26), p < 0.001]. IPW analysis revealed the association between hyperoxemia and prolonged ICU stay among patients not intubated at the ED [ICU-free days = 16 (12–22) vs 23 (19–26), p = 0.004], but not among those intubated at the ED [18 (9–20) vs 15 (8–23), p = 0.777]. In the hyperoxemia group, high inflammatory markers such as soluble RAGE and HMGB-1, as well as low lung-protective proteins such as surfactant protein D and Clara cell secretory protein, were associated with prolonged ICU stay. Conclusions Hyperoxemia until 3 h after hospital arrival was associated with prolonged ICU stay among severely injured trauma patients not intubated at the ED. Trial registration UMIN-CTR, UMIN000019588 . Registered on November 15, 2015.

Introduction Resuscitative 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 analysis The 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 dissemination This 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 number UMIN Clinical Trials Registry (UMIN000035458).

Abstract Background A recent randomised trial showed that recombinant thrombomodulin did not benefit patients who had sepsis with coagulopathy and organ dysfunction. Several recent studies suggested presence of clinical phenotypes in patients with sepsis and heterogenous treatment effects across different sepsis phenotypes. We examined the latent phenotypes of sepsis with coagulopathy and the associations between thrombomodulin treatment and the 28-day and in-hospital mortality for each phenotype. Methods This was a secondary analysis of multicentre registries containing data on patients (aged ≥ 16 years) who were admitted to intensive care units for severe sepsis or septic shock in Japan. Three multicentre registries were divided into derivation (two registries) and validation (one registry) cohorts. Phenotypes were derived using k-means with coagulation markers, platelet counts, prothrombin time/international normalised ratios, fibrinogen, fibrinogen/fibrin-degradation-products (FDP), D-dimer, and antithrombin activities. Associations between thrombomodulin treatment and survival outcomes (28-day and in-hospital mortality) were assessed in the derived clusters using a generalised estimating equation. Results Four sepsis phenotypes were derived from 3694 patients in the derivation cohort. Cluster dA (n = 323) had severe coagulopathy with high FDP and D-dimer levels, severe organ dysfunction, and high mortality. Cluster dB had severe disease with moderate coagulopathy. Clusters dC and dD had moderate and mild disease with and without coagulopathy, respectively. Thrombomodulin was associated with a lower 28-day (adjusted risk difference [RD]: − 17.8% [95% CI − 28.7 to − 6.9%]) and in-hospital (adjusted RD: − 17.7% [95% CI − 27.6 to − 7.8%]) mortality only in cluster dA. Sepsis phenotypes were similar in the validation cohort, and thrombomodulin treatment was also associated with lower 28-day (RD: − 24.9% [95% CI − 49.1 to − 0.7%]) and in-hospital mortality (RD: − 30.9% [95% CI − 55.3 to − 6.6%]). Conclusions We identified four coagulation marker-based sepsis phenotypes. The treatment effects of thrombomodulin varied across sepsis phenotypes. This finding will facilitate future trials of thrombomodulin, in which a sepsis phenotype with high FDP and D-dimer can be targeted.

Abstract Previous studies have shown inconsistent prognostic accuracy for mortality with both quick sequential organ failure assessment (qSOFA) and the systemic inflammatory response syndrome (SIRS) criteria. We aimed to validate the accuracy of qSOFA and the SIRS criteria for predicting in-hospital mortality in patients with suspected infection in the emergency department. A prospective study was conducted including participants with suspected infection who were hospitalised or died in 34 emergency departments in Japan. Prognostic accuracy of qSOFA and SIRS criteria for in-hospital mortality was assessed by the area under the receiver operating characteristic (AUROC) curve. Of the 1060 participants, 402 (37.9%) and 915 (86.3%) had qSOFA ≥ 2 and SIRS criteria ≥ 2 (given thresholds), respectively, and there were 157 (14.8%) in-hospital deaths. Greater accuracy for in-hospital mortality was shown with qSOFA than with the SIRS criteria (AUROC: 0.64 versus 0.52, difference + 0.13, 95% CI [+ 0.07, + 0.18]). Sensitivity and specificity for predicting in-hospital mortality at the given thresholds were 0.55 and 0.65 based on qSOFA and 0.88 and 0.14 based on SIRS criteria, respectively. To predict in-hospital mortality in patients visiting to the emergency department with suspected infection, qSOFA was demonstrated to be modestly more accurate than the SIRS criteria albeit insufficiently sensitive. Clinical Trial Registration: The study was pre-registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000027258).

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.

Abstract Current research regarding the association between body mass index (BMI) and altered clinical outcomes of sepsis in Asian populations is insufficient. We investigated the association between BMI and clinical outcomes using two Japanese cohorts of severe sepsis (derivation cohort, Chiba University Hospital, n = 614; validation cohort, multicenter cohort, n = 1561). Participants were categorized into the underweight (BMI

Abstract Background Frailty is associated with morbidity and mortality in patients admitted to intensive care units (ICUs). However, the characteristics of frail patients with suspected infection remain unclear. We aimed to investigate the characteristics and outcomes of frail patients with suspected infection in ICUs. Methods This is a secondary analysis of a multicenter cohort study, including 22 ICUs in Japan. Adult patients (aged ≥16 years) with newly suspected infection from December 2017 to May 2018 were included. We compared baseline patient characteristics and outcomes among three frailty groups based on the Clinical Frailty Scale (CFS) score: fit (score, 1–3), vulnerable (score, 4), and frail (score, 5–9). We conducted subgroup analysis of patients with sepsis defined as per Sepsis-3 criteria. We also produced Kaplan–Meier survival curves for 90-day survival. Results We enrolled 650 patients with suspected infection, including 599 (92.2%) patients with sepsis. Patients with a median CFS score of 3 (interquartile range [IQR] 3–5) were included: 337 (51.8%) were fit, 109 (16.8%) were vulnerable, and 204 (31.4%) were frail. The median patient age was 72 years (IQR 60–81). The Sequential Organ Failure Assessment scores for fit, vulnerable, and frail patients were 7 (IQR 4–10), 8 (IQR 5–11), and 7 (IQR 5–10), respectively (p = 0.59). The median body temperatures of fit, vulnerable, and frail patients were 37.5 °C (IQR 36.5 °C–38.5 °C), 37.5 °C (IQR 36.4 °C–38.6 °C), and 37.0 °C (IQR 36.3 °C–38.1 °C), respectively (p

Thermal inhalation injuries have been consistently shown to increase mortality in patients with burns. However, there is no established management strategy for this type of injury. Here, we present a case of extensive airway burns followed by tracheobronchial stenosis, which was successfully treated with extracorporeal membrane oxygenation and systemic corticosteroid administration. A 60-year-old man with burns on 6% of his total body surface area (second degree) and extensive airway burns in the lower respiratory tract was transferred to the emergency department. On the fifth day of admission, veno-venous extracorporeal membrane oxygenation (ECMO) was performed to manage the refractory respiratory failure due to bronchial obstruction by significant bronchial membrane edema and formation of a pseudomembrane in the damaged bronchi. Lung-rest management using ECMO lasted for 8 days. Thereafter, progressive multiple tracheobronchial stenoses were observed. Steroid therapy based on the regimen for the management of bronchial chondritis effectively improved the bronchial structure. Finally, the patient was successfully weaned from mechanical respiratory support. Our case shows that ECMO may be a useful strategy in patients with extensive lower respiratory tract inhalation injuries who may experience difficulty in maintaining their respiratory status. In addition, corticosteroid therapy might be an adjunctive therapy to delay the tracheobronchial stenosis caused by progressive granulation tissue formation.

Computed tomography (CT) is a sensitive and specific test for thoracic aortic injury, and is the choice of diagnostic test for adult patients. However, the diagnostic accuracy of conventional CT in pediatric patients has not been elucidated, and the diagnostic strategy has not been clarified. We present the case of an eight-year-old patient who had a thoracic injury, with left open pneumothorax, pulmonary contusion, and multiple left-sided rib fractures. Although the findings on conventional CT were insufficient either to diagnose or deny as having thoracic aortic injury, additional examination using electrocardiogram-gated CT angiography and three-dimensional reconstruction revealed a localized enlarged aortic diameter with an intimal flap. Electrocardiogram-gated CT may be useful for diagnosing thoracic aortic injury in pediatric patients.

Background 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. Methods 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). Recommendations 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.

Aim 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. Methods This study was a post‐hoc analysis of data from the dexmedetomidine for sepsis in the ICU Randomized Evaluation (DESIRE) trial. Patients were divided into propofol and midazolam groups based on continuously used drug, and sedation control between groups compared on day three. We assessed the incidence of delirium, length of ICU stay, number of ventilator‐free days within the first 28 days, and mortality after 28 days. Results The 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]). Conclusion 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.

Background The updated Surviving Sepsis Campaign guidelines recommend a 1-hour window for completion of a sepsis care bundle; however, the effectiveness of the hour-1 bundle has not been fully evaluated. The present study aimed to evaluate the impact of hour-1 bundle completion on clinical outcomes in sepsis patients. Methods This was a multicenter, prospective, observational study conducted in 17 intensive care units in tertiary hospitals in Japan. We included all adult patients who were diagnosed as having sepsis by Sepsis-3 and admitted to intensive care units from July 2019 to August 2020. Impacts of hour-1 bundle adherence and delay of adherence on risk-adjusted in-hospital mortality were estimated by multivariable logistic regression analyses. Results The final study cohort included 178 patients with sepsis. Among them, 89 received bundle-adherent care. Completion rates of each component (measure lactate level, obtain blood cultures, administer broad-spectrum antibiotics, administer crystalloid, apply vasopressors) within 1 hour were 98.9%, 86.2%, 51.1%, 94.9%, and 69.1%, respectively. Completion rate of all components within 1 hour was 50%. In-hospital mortality was 18.0% in the patients with and 30.3% in the patients without bundle-adherent care (p = 0.054). The adjusted odds ratio of non-bundle-adherent versus bundle-adherent care for in-hospital mortality was 2.32 (95% CI 1.09–4.95) using propensity scoring. Non-adherence to obtaining blood cultures and administering broad-spectrum antibiotics within 1 hour was related to in-hospital mortality (2.65 [95% CI 1.25–5.62] and 4.81 [95% CI 1.38–16.72], respectively). The adjusted odds ratio for 1-hour delay in achieving hour-1 bundle components for in-hospital mortality was 1.28 (95% CI 1.04–1.57) by logistic regression analysis. Conclusion Completion of the hour-1 bundle was associated with lower in-hospital mortality. Obtaining blood cultures and administering antibiotics within 1 hour may have been the components most contributing to decreased in-hospital mortality.

BackgroundThe updated Surviving Sepsis Campaign guidelines recommend a 1-hour window for completion of a sepsis care bundle; however, the effectiveness of the hour-1 bundle has not been fully evaluated. The present study aimed to evaluate the impact of hour-1 bundle completion on clinical outcomes in sepsis patients.MethodsThis was a multicenter, prospective, observational study conducted in 17 intensive care units in tertiary hospitals in Japan. We included all adult patients who were diagnosed as having sepsis by Sepsis-3 and admitted to intensive care units from July 2019 to August 2020. Impacts of hour-1 bundle adherence and delay of adherence on risk-adjusted in-hospital mortality were estimated by multivariable logistic regression analyses.ResultsThe final study cohort included 178 patients with sepsis. Among them, 89 received bundle-adherent care. Completion rates of each component (measure lactate level, obtain blood cultures, administer broad-spectrum antibiotics, administer crystalloid, apply vasopressors) within 1 hour were 98.9%, 86.2%, 51.1%, 94.9%, and 69.1%, respectively. Completion rate of all components within 1 hour was 50%. In-hospital mortality was 18.0% in the patients with and 30.3% in the patients without bundle-adherent care (p = 0.054). The adjusted odds ratio of non-bundle-adherent versus bundle-adherent care for in-hospital mortality was 2.32 (95% CI 1.09-4.95) using propensity scoring. Non-adherence to obtaining blood cultures and administering broad-spectrum antibiotics within 1 hour was related to in-hospital mortality (2.65 [95% CI 1.25-5.62] and 4.81 [95% CI 1.38-16.72], respectively). The adjusted odds ratio for 1-hour delay in achieving hour-1 bundle components for in-hospital mortality was 1.28 (95% CI 1.04-1.57) by logistic regression analysis.ConclusionCompletion of the hour-1 bundle was associated with lower in-hospital mortality. Obtaining blood cultures and administering antibiotics within 1 hour may have been the components most contributing to decreased in-hospital mortality.

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.

Abstract Background Elderly patients have a blunted host response, which may influence vital signs and clinical outcomes of sepsis. This study was aimed to investigate whether the associations between the vital signs and mortality are different in elderly and non-elderly patients with sepsis. Methods This was a retrospective observational study. A Japanese multicenter sepsis cohort (FORECAST, n = 1148) was used for the discovery analyses. Significant discovery results were tested for replication using two validation cohorts of sepsis (JAAMSR, Japan, n = 624; SPH, Canada, n = 1004). Patients were categorized into elderly and non-elderly groups (age ≥ 75 or

Abstract Background Diagnosing sepsis remains difficult because it is not a single disease but a syndrome with various pathogen- and host factor-associated symptoms. Sepsis-3 was established to improve risk stratification among patients with infection based on organ failures, but it has been still controversial compared with previous definitions. Therefore, we aimed to describe characteristics of patients who met sepsis-2 (severe sepsis) and sepsis-3 definitions. Methods This was a multicenter, prospective cohort study conducted by 22 intensive care units (ICUs) in Japan. Adult patients (≥ 16 years) with newly suspected infection from December 2017 to May 2018 were included. Those without infection at final diagnosis were excluded. Patient’s characteristics and outcomes were described according to whether they met each definition or not. Results In total, 618 patients with suspected infection were admitted to 22 ICUs during the study, of whom 530 (85.8%) met the sepsis-2 definition and 569 (92.1%) met the sepsis-3 definition. The two groups comprised different individuals, and 501 (81.1%) patients met both definitions. In-hospital mortality of study population was 19.1%. In-hospital mortality among patients with sepsis-2 and sepsis-3 patients was comparable (21.7% and 19.8%, respectively). Patients exclusively identified with sepsis-2 or sepsis-3 had a lower mortality (17.2% vs. 4.4%, respectively). No patients died if they did not meet any definitions. Patients who met sepsis-3 shock definition had higher in-hospital mortality than those who met sepsis-2 shock definition. Conclusions Most patients with infection admitted to ICU meet sepsis-2 and sepsis-3 criteria. However, in-hospital mortality did not occur if patients did not meet any criteria. Better criteria might be developed by better selection and combination of elements in both definitions. Trial registration UMIN000027452

Abstract Background Predisposing conditions and risk modifiers instead of causes and risk factors have recently been used as alternatives to identify patients at a risk of acute respiratory distress syndrome (ARDS). However, data regarding risk modifiers among patients with non-pulmonary sepsis is rare. Methods We conducted a secondary analysis of the multicenter, prospective, Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) cohort study that was conducted in 59 intensive care units (ICUs) in Japan during January 2016–March 2017. Adult patients with severe sepsis caused by non-pulmonary infection were included, and the primary outcome was having ARDS, defined as meeting the Berlin definition on the first or fourth day of screening. Multivariate logistic regression modeling was used to identify risk modifiers associated with ARDS, and odds ratios (ORs) and their 95% confidence intervals were reported. The following explanatory variables were then assessed: age, sex, admission source, body mass index, smoking status, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, steroid use, statin use, infection site, septic shock, and acute physiology and chronic health evaluation (APACHE) II score. Results After applying inclusion and exclusion criteria, 594 patients with non-pulmonary sepsis were enrolled, among whom 85 (14.3%) had ARDS. Septic shock was diagnosed in 80% of patients with ARDS and 66% of those without ARDS (p = 0.01). APACHE II scores were higher in patients with ARDS [26 (22–33)] than in those without ARDS [21 (16–28), p < 0.01]. In the multivariate logistic regression model, the following were independently associated with ARDS: ICU admission source [OR, 1.89 (1.06–3.40) for emergency department compared with hospital wards], smoking status [OR, 0.18 (0.06–0.59) for current smoking compared with never smoked], infection site [OR, 2.39 (1.04–5.40) for soft tissue infection compared with abdominal infection], and APACHE II score [OR, 1.08 (1.05–1.12) for higher compared with lower score]. Conclusions Soft tissue infection, ICU admission from an emergency department, and a higher APACHE II score appear to be the risk modifiers of ARDS in patients with non-pulmonary sepsis.

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

Abstract Background Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan. Methods This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0–60, 61–120, 121–180, 181–240, 241–360, and 361–1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with “hospital” as the grouping variable. Results Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55–189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48–164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39–180 min)] and longest in patients transferred from wards [120 min (62–226)]. Overall crude mortality was 23.4%, where patients in the 0–60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3–34.1%)], whereas those in the 61–120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5–26.6%)]. Differences in mortality were noted only between the 0–60 min and 61–120 min groups. Conclusions We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis.

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.

In diabetes mellitus (DM) patients, the morbidity of infectious disease is increased, and these infections can easily progress from local to systemic infection. Sepsis is a characteristic of organ failure related to microcirculation disorders resulting from endothelial cell injury, whose most frequent comorbidity in patients is DM. The aim of the present study was to evaluate the influence of infection on DM-induced microvascular damage on inflammation and pulmonary endothelial structure using an experimental endotoxemia model. Lipopolysaccharide (LPS; 15 mg/kg) was injected intraperitoneally into 10-week-old male C57BLKS/J Iar- +leprdb/leprdb (db/db) mice and into C57BLKS/J Iar–m + / + leprdb (db/ +) mice, which served as the littermate non-diabetic control. At 48 h after LPS administration, the survival rate of db/db mice (0%, 0/10) was markedly lower (P < 0.05) than that of the db/ + mice (75%, 18/24), whereas the survival rate was 100% in both groups 24 h after LPS administration. In control mice, CD11b-positive cells increased at 6 h after LPS administration; by comparison, the number of CD11b-positive cells increased gradually in db/db mice until 12 h after LPS injection. In the control group, the number of Iba-1-positive cells did not significantly increase before and at 6, 12, and 24 h after LPS injection. Conversely, Iba-1-positive cells continued to increase until 24 h after LPS administration, and this increase was significantly greater than that in the control mice. Expression of Ext1, Csgalnact1, and Vcan related to endothelial glycocalyx synthesis was significantly lower in db/db mice than in the control mice before LPS administration, indicating that endothelial glycocalyx synthesis is attenuated in db/db/mice. In addition, ultrastructural analysis revealed that endothelial glycocalyx was thinner in db/db mice before LPS injection. In conclusion, in db/db mice, the endothelial glycocalyx is already injured before LPS administration, and migration of inflammatory cells is both delayed and expanded. This extended inflammation may be involved in endothelial glycocalyx damage due to the attenuation of endothelial glycocalyx synthesis.