Efficacy of Carbapenems Compared With Noncarbapenem Broad-Spectrum Beta-Lactam Antibiotics as Initial Antibiotic Therapy Against Sepsis: A Nationwide Observational Study.

OBJECTIVES: As causative pathogens are not usually identified at the time of initiating antibiotics in sepsis, carbapenems are commonly used as an initial treatment. To reduce indiscriminate use of carbapenems, the efficacy of alternative empiric regimens, such as piperacillin-tazobactam and the fourth-generation cephalosporins, should be elucidated. This study aimed to evaluate survival effect associated with carbapenems as initial therapy for sepsis compared with these antibiotics. DESIGN: Multicenter retrospective observational study. SETTING: Tertiary hospitals in Japan. PATIENTS: Adult patients diagnosed as having sepsis from 2006 to 2019. INTERVENTIONS: Administration of carbapenems as initial antibiotic therapy. MEASUREMENTS AND MAIN RESULTS: This study used data of adult patients with sepsis extracted from a large-scale database in Japan. Patients were divided into two groups as follows: patients receiving carbapenems and patients receiving noncarbapenem broad-spectrum beta-lactam antibiotics as initial treatment. In-hospital mortality was compared between the groups by a logistic regression model adjusted by an inverse probability treatment weighting using propensity scores. To evaluate heterogeneity of effects according to patient characteristics, we also fitted logistic models in several subgroups. Among 7,392 patients with sepsis, 3,547 patients received carbapenems, and 3,845 patients received noncarbapenem agents. The logistic model showed no significant association between carbapenem therapy and lower mortality (adjusted OR 0.88, p = 0.108). Subgroup analyses suggested that there were significant survival benefits associated with carbapenem therapy in patients with septic shock, in ICUs, or with mechanical ventilation ( p for effect modifications: < 0.001, 0.014, and 0.105, respectively). CONCLUSIONS: Compared with the noncarbapenem broad-spectrum antibiotics, carbapenems as an initial therapy for sepsis were not associated with significantly lower mortality.

Impact of the hybrid emergency department on resuscitation strategies and outcomes in ventricular fibrillation.

BACKGROUND: The Hybrid emergency room (ER) is a novel resuscitation room that includes a whole-body computed tomography scanner and angiography system, which enables physicians to seamlessly conduct resuscitation, diagnosis and therapeutic interventions without patient transfer. This study aimed to assess the impact of the Hybrid ER on mortality in patients with ventricular fibrillation cardiac arrest. METHODS: This was a retrospective cohort study conducted in a tertiary hospital in Japan. We consecutively included adult cardiac arrest patients who were transferred to the emergency departments from January 2007 to May 2020, and were confirmed to be in ventricular fibrillation within 10 min from patient arrival. The study population was divided into two groups: the conventional group (from January 2007 to July 2011) and the Hybrid ER group (from August 2011 to May 2020). The primary endpoint of this study was defined as all-cause in-hospital death. Secondary endpoints included the frequency of extracorporeal cardiopulmonary resuscitation (ECPR) and percutaneous coronary intervention (PCI), and door-to-balloon time and door-to-ECPR time. RESULTS: We included 115 patients in the conventional group and 185 patients in the Hybrid ER group. In-hospital mortality was significantly decreased in the Hybrid ER group (adjusted hazard ratio, 0.79; 95% confidence interval 0.64, 0.97; p = 0.026). Door-to-ECPR time was significantly shorter in the Hybrid ER group (p < 0.001, Gehan-Breslow-Wilcoxon test), as was door-to-balloon time in this group (p = 0.004, Gehan-Breslow-Wilcoxon test). In interrupted time-series analyses, it was visually recognized that the ratio of patients who received ECPR and PCI increased, and door-to-ECPR time and door-to-balloon time were shortened from 2011 to 2012 (before and after installation of the Hybrid ER). CONCLUSION: Installation of the Hybrid ER was associated with a reduced time to ECPR and PCI and with a possible improvement in survival in patients with ventricular fibrillation cardiac arrest.

Timing of computed tomography imaging in adult patients with severe trauma: A nationwide cohort study in Japan.

PURPOSE: Computed tomography (CT) has become essential for the management of trauma patients. However, appropriate timing of CT acquisition remains undetermined. The purpose of this study was to assess the relationship between time to CT acquisition and mortality among adult patients with severe trauma. METHODS: We conducted a retrospective cohort study using data from the Japan Trauma Data Bank, which had 256 participating institutions from all over Japan between 2004 and 2018. Patients were categorized upon arrival as either severe trunk trauma with signs of shock or severe head trauma with coma and separately analyzed. Cases were further divided into three groups based on time elapsed between arrival at hospital and CT acquisition as immediate (0-29 min), intermediate (30-59 min), or late (≥60 min). Primary outcome was mortality on discharge, and multivariate logistic regression with adjusting for confounders was used for evaluation. RESULTS: A total of 8467 (3640 in immediate group, 3441 in intermediate group, 1386 in late group) with trunk trauma patients and 6762 (4367 in immediate group, 2031 in intermediate group, 364 in late group) with head trauma patients were eligible for analysis included in the trunk and head trauma groups, respectively. The trunk trauma patients with shock on hospital arrival was 56.4% (4773/8467), and the head trauma patients with deep coma upon EMS arrival was 44.2% (2988/6762). Mortality rate gradually increased from 5.7% to 15.8% with prolonged time to CT imaging among trunk trauma patients. Multivariate logistic regression for death on discharge among trunk trauma patients yielded an adjusted odds ratio of 1.79 (95% confidence interval: 1.42-2.27) for the late group compared to the immediate group. In contrast, among head trauma patients, an adjusted odds ratio was 0.93 (95% confidence interval: 0.71-1.20) for the late group compared to the immediate group. CONCLUSION: CT scan at or after 60 min was associated with increased death on discharge among patients with severe trunk trauma but not in those with severe head trauma.

Trends in the incidence and outcome of sepsis using data from a Japanese nationwide medical claims database-the Japan Sepsis Alliance (JaSA) study group.

BACKGROUND: Trends in the incidence and outcomes of sepsis using a Japanese nationwide database were investigated. METHODS: This was a retrospective cohort study. Adult patients, who had both presumed serious infections and acute organ dysfunction, between 2010 and 2017 were extracted using a combined method of administrative and electronic health record data from the Japanese nationwide medical claim database, which covered 71.5% of all acute care hospitals in 2017. Presumed serious infection was defined using blood culture test records and antibiotic administration. Acute organ dysfunction was defined using records of diagnosis according to the international statistical classification of diseases and related health problems, 10th revision, and records of organ support. The primary outcomes were the annual incidence of sepsis and death in sepsis per 1000 inpatients. The secondary outcomes were in-hospital mortality rate and length of hospital stay in patients with sepsis. RESULTS: The analyzed dataset included 50,490,128 adult inpatients admitted between 2010 and 2017. Of these, 2,043,073 (4.0%) patients had sepsis. During the 8-year period, the annual proportion of patients with sepsis across inpatients significantly increased (slope = + 0.30%/year, P < 0.0001), accounting for 4.9% of the total inpatients in 2017. The annual death rate of sepsis per 1000 inpatients significantly increased (slope = + 1.8/1000 inpatients year, P = 0.0001), accounting for 7.8 deaths per 1000 inpatients in 2017. The in-hospital mortality rate and median (interquartile range) length of hospital stay significantly decreased (P < 0.001) over the study period and were 18.3% and 27 (15-50) days in 2017, respectively. CONCLUSIONS: The Japanese nationwide data indicate that the annual incidence of sepsis and death in inpatients with sepsis significantly increased; however, the annual mortality rates and length of hospital stay in patients with sepsis significantly decreased. The increasing incidence of sepsis and death in sepsis appear to be a significant and ongoing issue.

Original experimental rat model of blast-induced mild traumatic brain injury: a pilot study.

OBJECTIVE: Diagnosing blast-induced mild traumatic brain injury (mTBI) is difficult due to minimal imaging findings. This study aimed to establish a rat model of behavioral abnormality caused by blast-induced mTBI and detect new findings for therapeutic intervention. METHODS: We used a bench-top blast wave generator with the blast wave exiting through a 20-mm I.D. nozzle aimed at the focused target. The blast wave was directed at the head of male Wistar rats under general anesthesia positioned prone 2.5 cm below the nozzle. Peak shock wave pressure was 646.2 ± 70.3 kPa. RESULTS: After blast injury, mTBI rats did not show the findings of brain hemorrhage or contusion macroscopically and on hematoxylin-eosin-stained frozen sections but did show anorexia and weight loss in the early post-injury phase. Behavioral experiments revealed short-term memory impairment at 2 weeks and depression-like behavior at 2 and 6 weeks. Diffusion-weighted ex vivo MRI showed high-intensity areas in layers of the bilateral hippocampus. Immunohistochemical analysis revealed accumulation of reactive microglia and GFAP-positive astrocytes in the same region and loss of NeuN-positive neurons in the hippocampal pyramidal cell layer. CONCLUSIONS: This model can reflect the pathophysiology of blast-induced mTBI and could potentially be used to develop therapeutic interventions in the future.

Significance of body temperature in elderly patients with sepsis.

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 < 75 years). We tested for association between vital signs (body temperature [BT], heart rate, mean arterial pressure, systolic blood pressure, and respiratory rate) and 90-day in-hospital mortality (primary outcome). RESULTS: In the discovery cohort, non-elderly patients with BT < 36.0 °C had significantly increased 90-day mortality (P = 0.025, adjusted hazard ratio 1.70, 95% CI 1.07-2.71). In the validation cohorts, non-elderly patients with BT < 36.0 °C had significantly increased mortality (JAAMSR, P = 0.0024, adjusted hazard ratio 2.05, 95% CI 1.29-3.26; SPH, P = 0.029, adjusted hazard ratio 1.36, 95% CI 1.03-1.80). These differences were not observed in elderly patients in the three cohorts. Associations between the other four vital signs and mortality were not different in elderly and non-elderly patients. The interaction of age and hypothermia/fever was significant (P < 0.05). CONCLUSIONS: In septic patients, we found mortality in non-elderly sepsis patients was increased with hypothermia and decreased with fever. However, mortality in elderly patients was not associated with BT. These results illuminate the difference in the inflammatory response of the elderly compared to non-elderly sepsis patients.

Complementary Role of Hypothermia Identification to the Quick Sequential Organ Failure Assessment Score in Predicting Patients With Sepsis at High Risk of Mortality: A Retrospective Analysis From a Multicenter, Observational Study.

BACKGROUND: Although the quick Sequential Organ Failure Assessment (qSOFA) has been recommended for identifying patients at higher risk of hospital death, it has only a 60% sensitivity for in-hospital mortality. On the other hand, hypothermia associates with increased mortality and organ failure in patients with sepsis. This study aimed to assess the predictive validity of qSOFA for identifying patients with sepsis at higher risk of multiple organ dysfunction or death and the complementary effect of hypothermia. METHODS: Patients with severe sepsis admitted to intensive care units (ICUs) were retrospectively analyzed. The predictive validities of qSOFA (≥2, positive) and the complementary effect of hypothermia (body temperature ≤36.5°C) for the identification of death or multiorgan dysfunction were evaluated. RESULTS: Of the 624 patients, 230 (36.9%) developed multiorgan dysfunction and 144 (23.1%) died within 28 days; 527 (84.5%) had a positive qSOFA. The 28-day mortality rates of patients with positive and negative qSOFA were 25.4% and 10.3%, respectively (P = .001). The rate of positive qSOFA was higher in patients with multiorgan dysfunction (sensitivity, 0.896; specificity, 0.185) and among patients who died within 28 days (sensitivity, 0.931; specificity, 0.181); 10 (6.9%) of 144 deaths were not identified. In cases of positive qSOFA without hypothermia, positive qSOFA + hypothermia, or negative qSOFA with hypothermia, the predictive value for 28-day mortality improved (sensitivity, 0.979). Among the 144 patients who died, only 3 were not identified. CONCLUSION: A qSOFA score ≥2 may identify >90% of 28-day deaths among patients with severe sepsis; hypothermia may complement the predictive ability of qSOFA.

Impact of Body Temperature Abnormalities on the Implementation of Sepsis Bundles and Outcomes in Patients With Severe Sepsis: A Retrospective Sub-Analysis of the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis and Trauma Study.

OBJECTIVES: To investigate the impact of body temperature on disease severity, implementation of sepsis bundles, and outcomes in severe sepsis patients. DESIGN: Retrospective sub-analysis. SETTING: Fifty-nine ICUs in Japan, from January 2016 to March 2017. PATIENTS: Adult patients with severe sepsis based on Sepsis-2 were enrolled and divided into three categories (body temperature < 36°C, 36-38°C, > 38°C), using the core body temperature at ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: Hypothermia was associated with a significantly higher disease severity, mortality risk, and lower implementation of sepsis bundles.

Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study.

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.

Prognostic Accuracy of Quick SOFA is different according to the severity of illness in infectious patients.

BACKGROUND: Sepsis-3 proposed the quick Sequential Organ Failure Assessment (qSOFA) to identify sepsis patients likely to have poor outcome. The clinical utility of qSOFA still remains controversial because its predictive accuracy for mortality is quite different across the validation studies. We hypothesized that one of the major causes for these controversial findings was the heterogeneity in severity across the studies, and evaluated the association between severity of illness and the prognostic accuracy of qSOFA. MATERIALS AND METHODS: This was a post hoc analysis of a prospective nationwide cohort of consecutive adult patients with sepsis in 59 intensive care units in Japan. Regression trees analysis for survival was used to classify patients according to severity of illness as determined by SOFA score on registration. We conducted receiver operating characteristic (ROC) analyses and evaluated the differences in the area under the ROC curve (AUROC). As a subgroup analysis, we conducted the above evaluations in emergency department (ED) and non-ED patients separately. RESULTS: We included 1114 patients fulfilling the criteria and classified them into three subsets according to severity. The AUROC for mortality was significantly different according to the severity of illness (p = 0.007), with the highest AUROC being in the low-severity subset (patients with SOFA score ≤ 7). Interestingly, our subgroup analysis revealed that a significant difference in the AUROC of qSOFA was observed only in ED patients. CONCLUSION: This study suggested that lower severity of illness was associated with the relatively higher prognostic accuracy of qSOFA, especially in ED patients.

Characteristics, management, and in-hospital mortality among patients with severe sepsis in intensive care units in Japan: the FORECAST study.

BACKGROUND: Sepsis is a leading cause of death and long-term disability in developed countries. A comprehensive report on the incidence, clinical characteristics, and evolving management of sepsis is important. Thus, this study aimed to evaluate the characteristics, management, and outcomes of patients with severe sepsis in Japan. METHODS: This is a cohort study of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) study, which was a multicenter, prospective cohort study conducted at 59 intensive care units (ICUs) from January 2016 to March 2017. We included adult patients with severe sepsis based on the sepsis-2 criteria. RESULTS: In total, 1184 patients (median age 73 years, interquartile range (IQR) 64-81) with severe sepsis were admitted to the ICU during the study period. The most common comorbidity was diabetes mellitus (23%). Moreover, approximately 63% of patients had septic shock. The median Sepsis-related Organ Failure Assessment (SOFA) score was 9 (IQR 6-11). The most common site of infection was the lung (31%). Approximately 54% of the participants had positive blood cultures. The compliance rates for the entire 3-h bundle, measurement of central venous pressure, and assessment of central venous oxygen saturation were 64%, 26%, and 7%, respectively. A multilevel logistic regression model showed that closed ICUs and non-university hospitals were more compliant with the entire 3-h bundle. The in-hospital mortality rate of patients with severe sepsis was 23% (21-26%). Older age, multiple comorbidities, suspected site of infection, and increasing SOFA scores correlated with in-hospital mortality, based on the generalized estimating equation model. The length of hospital stay was 24 (12-46) days. Approximately 37% of the patients were discharged home after recovery. CONCLUSION: Our prospective study showed that sepsis management in Japan was characterized by a high compliance rate for the 3-h bundle and low compliance rate for central venous catheter measurements. The in-hospital mortality rate in Japan was comparable to that of other developed countries. Only one third of the patients were discharged home, considering the aging population with multiple comorbidities in the ICUs in Japan. TRIAL REGISTRATION: UMIN-CTR, UMIN000019742 . Registered on 16 November 2015.

Assessment of mortality by qSOFA in patients with sepsis outside ICU: A post hoc subgroup analysis by the Japanese Association for Acute Medicine Sepsis Registry Study Group.

Quick sequential organ failure assessment (qSOFA) was proposed in the new sepsis definition (Sepsis-3). Although qSOFA was created to identify patients with suspected infection and likely to have poor outcomes, the clinical utility of qSOFA to screen sepsis has not been fully evaluated. We investigated the number of patients diagnosed as having severe sepsis who could not be identified by the qSOFA criteria and what clinical signs could complement the qSOFA score. This retrospective analysis of a multicenter prospective registry included adult patients with severe sepsis diagnosed outside the intensive care unit (ICU) by conventional criteria proposed in 2003. We conducted receiver operating characteristic (ROC) analyses to assess the predictive value for in-hospital mortality and compared clinical characteristics between survivors and non-survivors with qSOFA score ≤ 1 point (qSOFA-negative). Among 387 eligible patients, 63 (16.3%) patients were categorized as qSOFA-negative, and 10 (15.9%) of these patients died. The area under the ROC curve for the qSOFA score was 0.615, which was superior to that for the systemic inflammatory response syndrome score (0.531, P = 0.019) but inferior to that for the SOFA score (0.702, P = 0.005). Multivariate logistic regression analysis showed that hypothermia might be associated with poor outcome independently of qSOFA criteria. Our findings suggested that qSOFA had a suboptimal level of predictive value outside the ICU and could not identify 16.3% of patients who were once actually diagnosed with sepsis. Hypothermia might be associated with an increased risk of death that cannot be identified by qSOFA.

Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan.

BACKGROUND: Little evidence supports anticoagulant therapy as effective adjuvant therapy to reduce mortality overall in sepsis. However, several studies suggest that anticoagulant therapy may reduce mortality in specific patients. This study aimed to identify a subset of patients with high benefit profiles for anticoagulant therapy against sepsis. METHODS: This post hoc subgroup analysis of a nationwide multicentre retrospective registry was conducted in 42 intensive care units in Japan. Consecutive adult patients with sepsis were included. Treatment effects of anticoagulants, e.g. antithrombin, recombinant thrombomodulin, heparin, and protease inhibitors, were evaluated by stratifying patients according to disseminated intravascular coagulation (DIC) and Sequential Organ Failure Assessment (SOFA) score. Intervention effects of anticoagulant therapy on in-hospital mortality and bleeding complications were analysed using Cox regression analysis stratified by propensity scores. RESULTS: Participants comprised 2663 consecutive patients with sepsis; 1247 patients received anticoagulants and 1416 received none. After adjustment for imbalances, anticoagulant administration was significantly associated with reduced mortality only in subsets of patients diagnosed with DIC, whereas similar mortality rates were observed in non-DIC subsets with anticoagulant therapy. Favourable associations between anticoagulant therapy and mortality were observed only in the high-risk subset (SOFA score 13-17; adjusted hazard ratio 0.601; 95 % confidence interval 0.451, 0.800) but not in the subsets of patients with sepsis with low to moderate risk. Although the differences were not statistically significant, there was a consistent tendency towards an increase in bleeding-related transfusions in all SOFA score subsets. CONCLUSIONS: The analysis of this large database indicates anticoagulant therapy may be associated with a survival benefit in patients with sepsis-induced coagulopathy and/or very severe disease. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012543 ). Registered on 10 December 2013.

Benefit profile of recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis.

INTRODUCTION: The safety and efficacy of recombinant human soluble thrombomodulin (rhTM) have been demonstrated, with promising evidence suggestive of efficacy for patients with severe sepsis involving coagulopathy in a phase IIb randomized controlled trial. However, the benefit profiles of rhTM have not been elucidated. The purpose of this study was to explore whether patients with greater disease severity, determined according to the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, would experience treatment benefit from rhTM administration. METHODS: This was a post hoc, subgroup analysis of a multicenter retrospective cohort study conducted in three Japanese tertiary referral hospitals. Patients with sepsis-induced disseminated intravascular coagulation (DIC) who required ventilator management were included. We stratified patients into several strata according to disease severity, determined by APACHE II and SOFA scores, using classification and regression trees for survival data. Intervention effects, expressed as hazard ratios (HR), were analyzed using Cox regression analysis adjusted for a propensity model to detect subgroup heterogeneity of the effects of rhTM on in-hospital mortality. RESULTS: Participants were 162 patients with sepsis-induced DIC; 68 of these patients received rhTM and 94 did not. After adjusting for imbalances, rhTM administration was significantly associated with reduced mortality in high-risk patients (APACHE II: 24 to 29; HR: 0.281; 95% confidence interval (CI): 0.093 to 0.850; P = 0.025). A similar nonsignificant tendency was observed in the very high-risk subset (APACHE II: ≥30; HR: 0.529; 95% CI: 0.202 to 1.387; P = 0.195) but was not evident in the moderate-risk subset of patients (APACHE II: <24; HR: 0.814; 95% CI: 0.351 to 1.884; P = 0.630). A similar tendency was observed in analysis of SOFA scores (moderate-risk subset (SOFA: <11), P = 0.368; high-risk subset (SOFA: ≥11), P = 0.042). CONCLUSIONS: Survival benefit was observed with rhTM treatment in sepsis-induced DIC and high risk of death according to baseline APACHE II and SOFA scores.

A case of multiple organ injury resuscitated by collaboration of damage control surgery and interventional radiology in hybrid emergency room.

Background: Hybrid emergency room systems, namely hybrid ER (HER), enable us to perform computed tomography (CT), surgery, and interventional radiology (IVR) without patient transfer. HER significantly shortened the time to CT after arrival and allowed us to achieve early intervention, resulting in reduced mortality from exsanguination in patients with severe blunt trauma. Case Presentation: We encountered a patient diagnosed with left common iliac artery occlusion and dissection caused by blunt traumatic compressive abdominal injury with transection of the small intestine, kidney, and adrenal and pelvic ring fractures. Although the patient experienced cardiopulmonary arrest (CPA) immediately after CT, we performed damage control surgery (DCS) and IVR after temporary aortic occlusion in the HER and resuscitated the patient. Conclusion: The present case, in which rapid diagnosis and intervention were performed and the patient was successfully resuscitated, supports the efficacy of the HER system for managing severe blunt trauma.

Factor XIII Deficiency With Repeated Severe Postoperative Bleeding After Laparotomy: A Case Report.

Patients with factor XIII (FXIII) deficiency present with a bleeding tendency that is difficult to diagnose because their coagulation test results are normal. We herein report a case of a 74-year-old male who presented to our hospital in cardiac arrest. After resuscitation, he was found to have sigmoid volvulus and necrosis; therefore, an emergency laparotomy was performed. Intraoperative findings revealed an extensive strangulated ileus in addition to sigmoid volvulus. We performed resection without reconstruction and maintained open abdominal management (OAM) for six days. After abdominal closure, the patient experienced postoperative bleeding four times from the mesenteric transection; three of the bleeding episodes required open hemostasis. Since he had mild coagulopathy during each bleeding episode, FXIII deficiency was suspected and diagnosed. After administration of FXIII concentrate, the tendency to intraoperative bleeding improved significantly. FXIII deficiency should be considered in cases of repeated severe bleeding, even when coagulation tests reveal no major abnormalities.

Efficacy of unfractionated heparin in patients with moderate sepsis-induced coagulopathy: An observational study.

INTRODUCTION: The 2021 Surviving Sepsis Campaign guidelines recommend low-molecular-weight heparin for the prevention of venous thromboembolism in sepsis. However, observational studies suggest that anticoagulants as a whole may benefit severely ill sepsis patients with coagulopathy, but the optimal targets of unfractionated heparin remain unclear. This study investigated which sepsis patients could most benefit from unfractionated heparin. MATERIALS AND METHODS: In this retrospective observational study, we identified adult sepsis patients requiring urgent hospitalization from 2006 to 2019 using a large-scale Japanese medical database. Patients were divided into two groups: those receiving unfractionated heparin within 72 h of admission and those who did not. We compared in-hospital mortality, major bleeding complications, and thromboembolic events between these groups using a multivariate logistic regression model adjusted for patient and treatment variables. Additionally, we assessed the association between heparin administration and in-hospital mortality across various subgroups. RESULTS: Among 30,342 sepsis patients, 2520 received early heparin administration, and 27,822 did not. Multivariate logistic regression revealed a significant association between heparin and reduced in-hospital mortality (adjusted OR: 0.735, 95 % CI: 0.596-0.903) but no significant association with major bleeding and thromboembolic risk (adjusted OR: 1.137, 1.243; 95 % CI: 0.926-1.391, 0.853-1.788, respectively). Subgroup analyses suggested significant survival benefits associated with heparin only in the sepsis patients with moderate coagulopathy and sepsis-induced coagulopathy scores of 3 or 4 (adjusted OR: 0.452, 0.625; 95 % CI: 0.265-0.751, 0.410-0.940, respectively). CONCLUSIONS: Early heparin administration upon admission is associated with lower in-hospital mortality, especially in moderate sepsis-induced coagulopathy, and no significant increase in complications.

Association between hospital spending and in-hospital mortality of patients with sepsis based on a Japanese nationwide medical claims database study.

Background: The effect of hospital spending on the mortality rate of patients with sepsis has not yet been fully elucidated. We hypothesized that hospitals that consume more medical resources would have lower mortality rates among patients with sepsis. Methods: This retrospective study used administrative data from 2010 to 2017. The enrolled hospitals were divided into quartiles based on average daily medical cost per sepsis case. The primary and secondary outcomes were the average in-hospital mortality rate of patients with sepsis and the effective cost per survivor among the enrolled hospitals, respectively. A multiple regression model was used to determine the significance of the differences among hospital categories to adjust for baseline imbalances. Results: Among 997 hospitals enrolled in this study, the crude in-hospital mortality rates were 15.7% and 13.2% in the lowest and highest quartiles of hospital spending, respectively. After adjusting for confounding factors, the highest hospital spending group demonstrated a significantly lower in-hospital mortality rate than the lowest hospital spending group (coefficient = -0.025, 95% confidence interval [CI] -0.034 to -0.015; p < 0.0001). Similarly, the highest hospital spending group was associated with a significantly higher effective cost per survivor than the lowest hospital spending group (coefficient = 77.7, 95% CI 73.1 to 82.3; p < 0.0001). In subgroup analyses, hospitals with a small or medium number of beds demonstrated a consistent pattern with the primary test, whereas those with a large number of beds or academic affiliations displayed no association. Conclusions: Using a nationwide Japanese medical claims database, this study indicated that hospitals with greater expenditures were associated with a superior survival rate and a higher effective cost per survivor in patients with sepsis than those with lower expenditures. In contrast, no correlations between hospital spending and mortality were observed in hospitals with a large number of beds or academic affiliations.

Epidemiology and patterns of empiric antimicrobial therapy practice in patients with community-onset sepsis using data from a Japanese nationwide medical claims database-the Japan Sepsis Alliance (JaSA) study group.

Objectives: We aimed to describe empiric antimicrobial options for patients with community-onset sepsis using nationwide real-world data from Japan. Methods: This retrospective cohort study used nationwide Japanese data from a medical reimbursement system database. Patients aged ≥20 years with both presumed infections and acute organ dysfunction who were admitted to hospitals from the outpatient department or emergency department between 2010 and 2017 were enrolled. We described the initial choices of antimicrobials for patients with sepsis stratified by intensive care unit (ICU) or ward. Results: There were 1,195,741 patients with community-onset sepsis; of these, 1,068,719 and 127,022 patients were admitted to the wards and ICU, respectively. Third-generation cephalosporins and carbapenem were most commonly used for patients with community-onset sepsis. We found that 1.7% and 6.0% of patients initially used antimicrobials for methicillin-resistant Staphylococcus aureus coverage in the wards and ICU, respectively. Although half of the patients initially used antipseudomonal agents, only a few patients used a combination of antipseudomonal agents. Moreover, few patients initially used a combination of antimicrobials to treat methicillin-resistant Staphylococcus aureus and Pseudomonas sp. Conclusion: Third-generation cephalosporins and carbapenem were most frequently used for patients with sepsis. A combination therapy of antimicrobials for drug-resistant bacteria coverage was rarely provided to these patients.

Effects of Concomitant Traumatic Spinal Cord and Brain Injury on In-Hospital Mortality: A Retrospective Analysis of a Nationwide Trauma Registry in Japan.

Isolated traumatic spinal cord injury (t-SCI) and traumatic brain injury (TBI) represent significant public health concerns, resulting in long-term disabilities and necessitating sophisticated care, particularly when occurring concurrently. The impact of these combined injuries, while crucial in trauma management, on clinical, socioeconomic, and health care outcomes is largely unknown. To address this gap, our secondary retrospective cohort study used data from the Japan Trauma Data Bank, covering patients enrolled over a 13-year period (2006-2018), to elucidate the effects of concurrent t-SCI and TBI on in-hospital mortality. Data on patient demographics, injury characteristics, treatment modalities, and outcomes were analyzed. Multivariate logistic regression analysis was performed to examine prognostic variables associated with in-hospital mortality, including interaction terms between t-SCI severity and TBI presence. This study included 91,983 patients with neurotrauma, with a median age of 62 years (69.7% men). Among the patients, 9,018 (9.8%) died in the hospital. Concomitant t-SCI and TBI occurred in 2,954 (3.2%) patients. t-SCI only occurred in 9,590 (10.4%) patients, whereas TBI only occurred in the majority of these cases (79,439, 86.4%). Multivariate logistic regression analysis revealed age; sex; total number of comorbidities; systolic blood pressure at presentation; Glasgow coma scale score at presentation; and Abbreviated Injury Scale (AIS) scores for head, face, chest, abdomen, cervical-SCI, thoracic-SCI, and lumbar-SCI as significant independent factors for in-hospital mortality. The odds ratio of cervical-SCI × head AIS as an interaction term was 0.85 (95% confidence interval: 0.77-0.95), indicating a negative interaction. In conclusion, we identified 12 factors associated with in-hospital mortality in patients with t-SCI. In addition, the negative interaction between cervical t-SCI and TBI suggests that the presence of t-SCI in patients with TBI may be underestimated. This study highlights the importance of early recognition and comprehensive management of these complex trauma conditions while considering the possibility of concomitant t-SCI in patients with TBI.