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Purpose Sex-based differences in post-traumatic mortality have been widely discussed for quite some time. We hypothesized that age-related pathophysiologic changes would affect sex-based differences in post-traumatic mortality and aimed to verify the hypothesis using a nationwide trauma registry in Japan. Methods This was a retrospective analysis of trauma patients registered in The Japanese Trauma Data Bank. We stratified the study population into the following three subsets based on age: (1) pediatric subset (age ≤ 14), (2) adult subset (age 15–50) and (3) senior adult subset (age ≥ 51). We evaluated both sex-based differences in mortality in each subset separately using multivariate logistic regression analysis and the two-way interaction effect for predicted survival between the continuous increase of age and the sexes using a nonlinear multivariate regression model. Results We included 122,819 trauma patients who fulfilled the inclusion criteria and classified them into the 3 subsets according to age. Male patients were more likely to die compared to female patients only in the senior adult subset (adjusted odds ratio: 1.26; 95% confidence interval: 1.18–1.36), whereas there were no statistically significant differences in the other two subsets. Furthermore, non-linear logistic regression analysis revealed that predicted survival probability in male patients decreased more sharply in accordance with the increase of age compared to that in female patients (p for interaction: 0.051). Conclusion Age-related change in post-traumatic mortality was significantly different between males and females, and male patients had a relatively higher risk of death in the older population.

Introduction The rapid increase of extended-spectrum beta-lactamase (ESBL)-producing pathogens makes it difficult to choose appropriate antimicrobials in patients with Gram-negative bacterial infection. The Cica-beta reagent (Kanto Chemical, Tokyo, Japan) is a chromogenic test that detects ESBLs from bacterial colonies. This study aimed to reveal whether Cica-beta reagent could detect ESBLs directly from urine samples to facilitate rapid diagnosis of antibiotic susceptibility. Methods A prospective study was conducted from July 2019 to November 2019. Patients in whom urine culture tests were performed were eligible. Each urine sample was centrifuged, and the pellet was mixed with Cica-beta reagent. The test was considered positive when the enzymatic reaction turned from yellow to red or orange. Results In total, 350 urine samples were analysed. Urinary tract infection (UTI) was diagnosed in 214 patients. ESBL-producing Enterobacterales were isolated from 79 samples. The Cica-beta test showed sensitivity of 79.8% and specificity of 99.3% in patients with Gram-negative bacteriuria. Sensitivity and specificity improved to 90.2% and 100%, respectively, in patients with UTI. Conclusion The Cica-beta test could be an efficient test for the detection of ESBL-producing pathogens in urine. By providing immediate information about ESBLs, it might be a useful point-of-care test to guide appropriate antimicrobial use in patients with UTI.

Objectives: One of the most significant features of poor prognosis in COVID-19 is pulmonary fibrosis. Nintedanib is a new antifibrotic agent that interferes with processes of pulmonary fibrosis. This study aimed to investigate the efficacy and safety of nintedanib in COVID-19. Methods: This was an interventional study in which adult patients with COVID-19 requiring mechanical ventilation were consecutively enrolled. The primary endpoint was 28-day mortality after the initiation of mechanical ventilation. The secondary endpoints were length of mechanical ventilation, volume of lung injury, and the incidence of gastrointestinal adverse events and acute liver failure. Results: Thirty patients with COVID-19 underwent nintedanib therapy. We included 30 patients not receiving nintedanib as the historical control group. There were no significant differences in 28-day mortality between the groups (23.3% vs 20%, P = 0.834). Lengths of mechanical ventilation were significantly shorter in the nintedanib group (P = 0.046). Computed tomography volumetry showed that the percentages of high-attenuation areas were significantly lower in the nintedanib group at liberation from mechanical ventilation (38.7% vs 25.7%, P = 0.027). There were no significant differences in the adverse events. Conclusions: The administration of nintedanib may offer potential benefits for minimizing lung injury in COVID-19.

Background Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. Methods A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80–85 mmHg (high-target) and 65–70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients’ condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 μg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. Discussion The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. Trial registration UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

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.

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

Background There have been no clinical studies to sufficiently reveal the interaction effect generated by combinations of injury regions of multiple injuries. We hypothesized that certain combinations of trauma regions might lead to increased risk of traumatic death and aimed to verify this hypothesis using a nationwide trauma registry in Japan. Materials and methods This was a retrospective study of trauma patients registered in the Japan Trauma Data Bank between 2004 and 2017. We included patients who suffered blunt trauma with an Injury Severity Score of 16 or more. The trauma was classified into four regions (head, chest, abdomen, and extremities), and a multivariable logistic regression analysis was performed that included interaction terms derived from the combination of two regions as covariates. Results We included 78,280 trauma patients in this study. Among them, 16,100 (20.6%) patients were discharged to death. Multivariable logistic regression showed the odds ratio (OR) of in-hospital death compared with patients without injury of an Abbreviated Injury Scale score of 3 or more in each injured region as follows: head score, 2.31 (95% confidence interval [CI], 2.13-2.51); chest score, 2.28 (95% CI, 2.17-2.39); abdomen score, 1.68 (95% CI, 1.56-1.82); and extremities score, 1.84 (95% CI, 1.76-1.93), respectively. In addition, the ORs of the statistically significant interaction terms were as follows: head-chest 1.29 (95% CI, 1.13-1.48), chest-abdomen 0.77 (95% CI, 0.67-0.88), chest-extremities 1.95 (95% CI, 1.77-2.14), and abdomen-extremities 0.70 (95% CI, 0.62-0.79), respectively. Conclusion In this population, among patients with multiple injuries, a combination of head-chest trauma and chest-extremities trauma was shown to increase the risk of traumatic death. Level of evidence Prognostic, Level III.

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

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 Results In the discovery cohort, non-elderly patients with BT P = 0.025, adjusted hazard ratio 1.70, 95% CI 1.07–2.71). In the validation cohorts, non-elderly patients with BT 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 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.

The clinical implications of bacteremia among septic patients remain unclear, although a vast amount of data have been accumulated on sepsis. We aimed to compare the clinical characteristics and outcomes of severe sepsis patients with and without bacteremia. This secondary analysis of a multicenter, prospective cohort study included 59 intensive care units (ICUs) in Japan between January 2016 and March 2017. The study cohort comprised 1,184 adults (aged ≥ 16 years) who were admitted to an ICU with severe sepsis and diagnosed according to the Sepsis-2 criteria. Of 1,167 patients included in the analysis, 636 (54.5%) had bacteremia. Those with bacteremia had significantly higher rates of septic shock (66.4% vs. 58.9%, p = 0.01) and higher sepsis severity scores, including the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Sequential Organ Failure Assessment (SOFA). No significant difference in in-hospital mortality was seen between patients with and without bacteremia (25.6% vs. 21.0%, p = 0.08). In conclusion, half of severe sepsis patients in ICUs have bacteremia. Although patients with bacteremia had more severe state, between-group differences in patient-centered outcomes, such as in-hospital mortality, have not been fully elucidated.

ObjectivesThis study aimed to examine the difference in mortality from serious road traffic injuries during the National Traffic Safety Campaign compared with other periods and identify the common mechanisms of injury by age group in Japan.DesignA retrospective review of Japan Trauma Data Bank (JTDB).SettingA total of 280 participating major emergency institutions across Japan.ParticipantsPatients with road traffic injuries registered in JTDB between 2004 and 2018 were recruited in the study. We included patients injured by traffic crashes during the National Traffic Safety Campaigns and controls using a double control method. The National Traffic Safety Campaign comprises 10 consecutive days in spring and fall (20 days in each year), and controls was the same calendar days 2 weeks before and after the days in the National Traffic Safety Campaigns (40 days in each year) to control for weekday, seasonal and yearly trends.Primary and secondary outcome measuresThe primary outcome was in-hospital mortality. The secondary outcome was the incidences of severe traffic injury.ResultsAmong 126 857 patients recorded as road traffic injuries in JTDB, we identified 6181 patients (21 cases per day) with injuries occurring during the National Traffic Safety Campaigns and 12 382 controls (21 cases per day). The overall in-hospital mortality was 11.4%. We did not observe a significant difference in in-hospital mortality between the groups (11.8% vs 11.1%) with an adjusted OR of 1.05 (95% CI 0.95 to 1.16). The most common mechanism of injury in each age group was bicycle crash among children, motorcycle crash among adults and pedestrian among the elderly.ConclusionsWe found no change in the incidence of severe traffic injury or in-hospital mortality during the National Traffic Safety Campaign in Japan. Serious road trauma was high for bicycles among children, motorcycles among adults and pedestrian among the elderly.

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.

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 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 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.

This study aimed to assess the value of quick sequential organ failure assessment (qSOFA) combined with other risk factors in predicting in-hospital mortality in patients presenting to the emergency department with suspected infection. This post-hoc analysis of a prospective multicenter study dataset included 34 emergency departments across Japan (December 2017 to February 2018). We included adult patients (age ≥16 years) who presented to the emergency department with suspected infection. qSOFA was calculated and recorded by senior emergency physicians when they suspected an infection. Different types of sepsis-related risk factors (demographic, functional, and laboratory values) were chosen from prior studies. A logistic regression model was used to assess the predictive value of qSOFA for in-hospital mortality in models based on the following combination of predictors: 1) qSOFA-Only; 2) qSOFA+Age; 3) qSOFA+Clinical Frailty Scale (CFS); 4) qSOFA+Charlson Comorbidity Index (CCI); 5) qSOFA+lactate levels; 6) qSOFA+Age+CCI+CFS+lactate levels. We calculated the area under the receiver operating characteristic curve (AUC) and other key clinical statistics at Youden’s index, where the sum of sensitivity and specificity is maximized. Following prior literature, an AUC >0.9 was deemed to indicate high accuracy; 0.7–0.9, moderate accuracy; 0.5–0.7, low accuracy; and 0.5, a chance result. Of the 951 patients included in the analysis, 151 (15.9%) died during hospitalization. The AUC for predicting in-hospital mortality was 0.627 (95% confidence interval [CI]: 0.580−0.673) for the qSOFA-Only model. Addition of other variables only marginally improved the model’s AUC; the model that included all potentially relevant variables yielded an AUC of only 0.730 (95% CI: 0.687–0.774). Other key statistic values were similar among all models, with sensitivity and specificity of 0.55−0.65 and 0.60−0.75, respectively. In this post-hoc data analysis from a prospective multicenter study based in Japan, combining qSOFA with other sepsis-related risk factors only marginally improved the model’s predictive value.

Background: Disseminated intravascular coagulation (DIC) commonly complicates sepsis and considerably worsens mortality. Recent studies suggested that anticoagulant therapies improved mortality only in specific sepsis populations, and key pathologies for selecting optimal targets needed to be identified. Anticoagulant activities were naturally altered with aging. This study aimed to evaluate age-related differences in efficacy of anticoagulant therapies in sepsis.Methods: This post hoc analysis of a nationwide multicenter cohort study was conducted in 42 intensive care units in Japan. Adult patients with septic DIC were divided into anticoagulant and control groups. Age-related changes in predicted mortality in both groups were compared using a logistic regression model including two-way interaction terms. Patients were also stratified into three subsets based on age, and propensity score-adjusted Cox regression analyses were conducted to examine survival effect of anticoagulants in each subset.Results: We included 1432 patients with septic DIC; 867 patients received anticoagulants and 565 received none. Age-related change in predicted mortality was significantly different between groups (p for interaction = 0.013), and the gap between groups was broad in the younger population. Similarly, in Cox regression analyses, anticoagulant therapies were associated with significantly lower mortality in the subsets of age ≤60 and 60-79 (hazard ratios = 0.461, 0.617, p = 0.007, 0.005, respectively), whereas there was no difference in survival between the groups in the subsets of age ≥80.Conclusion: The efficacy of anticoagulant therapies for septic DIC might be associated with patient age.

Purpose Posttraumatic meningitis is one of the severe complications that can result in increased mortality and longer hospital stay among trauma patients. Factors such as cerebrospinal fluid (CSF) fistula and basilar skull fracture are associated with posttraumatic meningitis. However, it remains unclear whether procedures such as burr hole surgery in the emergency department and decompressive craniectomy are associated with posttraumatic meningitis. The aim of this study was to assess factors associated with posttraumatic meningitis with a nationwide hospital-based trauma registry in Japan. Methods This was a retrospective observational study with a 12-year study period from January 2004 to December 2015. We included trauma patients registered in the Japanese Trauma Data Bank, whose head Abbreviated Injury Scale score was ≥ 3 in this study. The main endpoint was the occurrence of meningitis during hospitalization. Multivariable logistic regression analysis was used to assess independent parameters associated with posttraumatic meningitis such as CSF fistula, burr hole surgery in the emergency department, and decompressive craniectomy. Results Among 60,390 head injury patients with head AIS score 3 or more, 284 (0.5%) patients had posttraumatic meningitis. Factors associated with posttraumatic meningitis were burr hole surgery in the emergency department (adjusted odds ratio [AOR] 2.158 [95% confidence interval (CI) 1.401–3.325]), decompressive craniectomy (AOR 2.123 [95% CI 1.506–2.993]), external ventricular drainage (AOR 1.843 [95% CI, 1.157–2.935]), CSF leakage (AOR 3.328 [95% CI 2.205–5.022]), and basilar skull fracture (AOR 1.651 [95% CI 1.178–2.314]). Conclusions In this population of trauma patients, burr hole surgery in the emergency department and decompressive craniectomy was associated with posttraumatic meningitis.

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

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

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score-matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.

The diagnostic criteria of overt disseminated intravascular coagulation (DIC) were established by the International Society on Thrombosis and Haemostasis (ISTH) in 2001. Since then, DIC has long been associated with adverse outcomes. However, recent advances in sepsis shed light on the role of coagulation disorders in the progression of sepsis. Currently, inflammation and coagulation are recognized as the two drivers that promote organ dysfunction in sepsis and septic shock. The ISTH has published new diagnostic criteria for improved management, namely sepsis-induced coagulopathy (SIC), in 2017. SIC is a pragmatic scoring system composed of platelet count, prothrombin time, and organ dysfunction score to detect the early-stage of sepsis-associated DIC. Since overt DIC represents an uncompensated coagulation disorder, a two-step approach using SIC and overt DIC criteria is a novel strategy to evaluate the severity and manage this challenging complication. Although there is no globally agreed on anticoagulant therapy for DIC, the Japanese Surviving Sepsis Campaign Guidelines 2020 recommend using antithrombin and recombinant thrombomodulin for sepsis associated DIC. Since research in this area has been previously reported, an international collaborative study is necessary to develop future diagnostic tools and treatment strategies.

Glycemic control strategies for sepsis have changed significantly over the last decade, but their impact on dysglycemia and its associated outcomes has been poorly understood. In addition, there is controversy regarding the detrimental effects of hyperglycemia in sepsis. To evaluate the incidence and risks of dysglycemia under current strategy, we conducted a preplanned subanalysis of the sepsis cohort in a prospective, multicenter FORECAST study. A total of 1,140 patients with severe sepsis, including 259 patients with pre-existing diabetes, were included. Median blood glucose levels were approximately 140 mg/dL at 0 and 72 h indicating that blood glucose was moderately controlled. The rate of initial and late hyperglycemia was 27.3% and 21.7%, respectively. The rate of early hypoglycemic episodes during the initial 24 h was 13.2%. Glycemic control was accompanied by a higher percentage of initial and late hyperglycemia but not with early hypoglycemic episodes, suggesting that glycemic control was targeted at excess hyperglycemia. In nondiabetic patients, late hyperglycemia (hazard ratio, 95% confidence interval; P value: 1.816, 1.116-2.955, 0.016) and early hypoglycemic episodes (1.936, 1.180-3.175, 0.009) were positively associated with in-hospital mortality. Further subgroup analysis suggested that late hyperglycemia and early hypoglycemic episodes independently, and probably synergistically, affect the outcomes. In diabetic patients, however, these correlations were not observed. In conclusion, a significantly high incidence of dysglycemia was observed in our sepsis cohort under moderate glycemic control. Late hyperglycemia in addition to early hypoglycemia was associated with poor outcomes at least in nondiabetic patients. More sophisticated approaches are necessary to reduce the incidence of these serious complications.

The aim of this study was to describe epidemiologic features of pediatric blunt renal trauma. We performed a retrospective analysis using the Japan Trauma Data Bank over 15 years. We included patients younger than 18 years with blunt renal trauma. We analyzed temporal trends and variations across age groups in patient characteristics, intervention, and in-hospital mortality. We also assessed factors associated with in-hospital mortality. We identified 435 pediatric patients with blunt renal trauma. Their median age was 14 years and median Injury Severity Score (ISS) was 17. The most common mechanism of injury was traffic accident in all age groups. Nephrectomy was performed in 3.2%, and the overall in-hospital mortality was 4.6%, both of which showed decreasing trends. The most common mechanism of injury by age group was a pedestrian accident in infants/toddlers/preschoolers (43.5%), pedestrian accident in middle childhood (18.5%), bicycle accident in young teens (24.7%), and motorcycle accident in teenagers (41.2%). Sports-related injury was common in young teens (23.3%) and teenagers (15.2%). Factors such as ISS, shock, concomitant injury, and nephrectomy were associated with high in-hospital mortality. We described decreasing trends in nephrectomy and in-hospital mortality in pediatric blunt renal trauma and found traffic accident and sports-related injury were common in the pediatric population in Japan.

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

The hybrid emergency room (ER) system is a novel trauma workflow that uses angio-computed tomography equipment in a trauma resuscitation room. Although the hybrid ER system decreases time to start surgery and endovascular treatments and improves mortality, the optimal target benefitting from this system remained unclear. We aimed to identify a subset of trauma patients likely to receive the greatest benefits from the hybrid ER.This retrospective cohort study was conducted in a tertiary hospital in Japan from August 2007 to January 2020. We consecutively included severe adult blunt trauma patients (Injury Severity Score [ISS], ≥16) and divided them into two groups: conventional group (August 2007 to July 2011) and hybrid ER (August 2011 to January 2020) group. We evaluated the association between the hybrid ER group and 28-day mortality using multivariable logistic regression analysis. The 28-day mortality trend during the study period was evaluated with restricted cubic spline analysis. To evaluate heterogeneity of effects within various patient severities, we evaluated whether the patients' ISS modified the effect of the hybrid ER on survival.Among 1,050 trauma patients, the conventional group comprised 360 patients and the hybrid ER group comprised 690 patients. Injury Severity Score and probability of survival (Ps) were not significantly different between the groups. Twenty-eight-day mortality was significantly lower in the hybrid ER group (Ps-adjusted odds ratio, 0.48; 95% confidence interval, 0.32-0.71; p0.001). Restricted cubic spline analysis revealed that Ps-adjusted 28-day mortality sharply decreased approximately 200 days after installation of the hybrid ER. Increase of survival probabilities according to the increase of ISS was significantly improved in hybrid ER group (p = 0.014). Because ISS increased to25, survival probabilities in the hybrid ER group were higher compared with those in the conventional group.The hybrid ER may improve posttraumatic mortality, especially in patients with higher baseline severity.Therapeutic/care management, level IV.

Purpose The aim of this study was to assess the effect of fluid administration by emergency life-saving technicians (ELST) on the prognosis of traffic accident patients by using a propensity score (PS)-matching method. Methods The study included traffic accident patients registered in the JTDB database from January 2016 to December 2017. The main outcome was hospital mortality, and the secondary outcome was cardiopulmonary arrest on hospital arrival (CPAOA). To reduce potential confounding effects in the comparisons between two groups, we estimated a propensity score (PS) by fitting a logistic regression model that was adjusted for 17 variables before the implementation of fluid administration by ELST at the scene. Results During the study period, 10,908 traffic accident patients were registered in the JTDB database, and we included 3502 patients in this study. Of these patients, 142 were administered fluid by ELST and 3360 were not administered fluid by ELST. After PS matching, 141 patients were selected from each group. In the PS-matched model, fluid administration by ELST at the scene was not associated with discharge to death (crude OR: 0.859 [95% CI, 0.500–1.475]; p = 0.582). However, the fluid group showed statistically better outcome for CPAOA than the no fluid group in the multiple logistic regression model (adjusted OR: 0.231 [95% CI, 0.055–0.967]; p = 0.045). Conclusion In this study, fluid administration to traffic accident patients by ELST was associated not with hospital mortality but with a lower proportion of CPAOA.

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 p = 0.060). In the primary analysis, multivariate analysis adjusted for baseline imbalance revealed that patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.031, adjusted odds ratio [OR] 1.91, 95% confidence interval [CI] 1.06–3.46). In a repeated analysis using a multicenter validation cohort (underweight n = 343, non-underweight n = 1218), patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.045, OR 1.40, 95% CI 1.00–1.97). In conclusion, patients with a BMI

Supplemental Digital Content is available in the text, This study aimed to identify prognostic factors for severe sepsis-related in-hospital mortality using the structural equation model (SEM) analysis with statistical causality. Sepsis data from the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma study (FORECAST), a multicenter cohort study, was used. Forty seven observed variables from the database were used to construct 4 latent variables. SEM analysis was performed on these latent variables to analyze the statistical causality among these data. This study evaluated whether the variables had an effect on in-hospital mortality. Overall, 1148 patients were enrolled. The SEM analysis showed that the 72-hour physical condition was the strongest latent variable affecting mortality, followed by physical condition before treatment. Furthermore, the 72-hour physical condition and the physical condition before treatment strongly influenced the Sequential Organ Failure Assessment (SOFA) score with path coefficients of 0.954 and 0.845, respectively. The SOFA score was the strongest variable that affected mortality after the onset of severe sepsis. The score remains the most robust prognostic factor and can facilitate appropriate policy development on care.

Introduction Polymyxin B hemoperfusion (PMX-HP) is an adjuvant therapy for sepsis or septic shock that removes circulating endotoxin. However, PMX-HP has seldom achieved expectations in randomized trials targeting nonspecific overall sepsis patients. If used in an optimal population, PMX-HP may be beneficial. This study aimed to identify the optimal population for PMX-HP in patients with septic shock. Methods We used a prospective nationwide cohort targeting consecutive adult patients with severe sepsis (Sepsis-2) in 59 intensive care units in Japan. Associations between PMX-HP therapy and in-hospital mortality were assessed using multivariable Cox proportional hazard regression models. To identify best targets for PMX-HP, we developed a non-linear restricted cubic spline model including two-way interaction term (treatment × Acute Physiology and Chronic Health Evaluation [APACHE] II score/Sequential Organ Failure Assessment [SOFA] score) and three-way interaction term (treatment × age × each score). Results The final study cohort comprised 741 sepsis patients (92 received PMX-HP, 625 did not). Cox proportional hazards regression model adjusted for the covariates suggested no association between PMX-HP therapy and improved mortality overall. Effect modification of PMX-HP by APACHE II score was statistically significant (P for interaction = 0.189) but non-significant for SOFA score (P for interaction = 0.413). Three-way interaction analysis revealed suppressed risk hazard in the PMX-HP group versus control group only in septic shock patients with high age and in the most severe subset of both scores, whereas increased risk hazard was observed in those with high age but in the lower severity subset of both scores. Conclusions Our results suggested that although PMX-HP did not reduce in-hospital mortality among overall septic shock patients, it may benefit a limited population with high age and higher disease severity.

Background Dysglycemia is frequently observed in patients with sepsis. However, the relationship between dysglycemia and outcome is inconsistent. We evaluate the clinical characteristics, glycemic abnormalities, and the relationship between the initial glucose level and mortality in patients with sepsis. Methods This is a retrospective sub-analysis of a multicenter, prospective cohort study. Adult patients with severe sepsis (Sepsis-2) were divided into groups based on blood glucose categories (

Background: Antithrombin and recombinant human thrombomodulin (rhTM) are individually reported to improve survival in sepsis-induced disseminated intravascular coagulation (DIC). However, continuing controversy exists as to which agent is superior and whether concomitant therapy is superior to individual administration. Methods: This post hoc analysis included adult patients with sepsis-induced DIC from a nationwide multicenter registry database in Japan. We categorized patients into 4 groups: patients who received (1) individual administration of antithrombin, (2) individual administration of rhTM, (3) both, and (4) neither. In-hospital mortality was compared between every 2 groups among the 4 groups by Cox proportional hazards model adjusted with propensity scores. Results: In total, 1432 patients with sepsis-induced DIC were included. Although both antithrombin and rhTM were associated better outcome compared with no anticoagulants, mortality benefits were similar between each individual anticoagulant. Similarly, no significant difference in mortality was detected between individual administrations and concomitant therapy. Conclusion: Antithrombin and rhTM might have comparable efficacy in reducing mortality in patients with sepsis; however, concomitant therapy appeared to offer no additional survival benefit.

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.

To evaluate the efficacy and safety of direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) therapy in patients with sepsis.A systematic review and meta-analysis of four major databases: Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, and Science Citation Index Expanded.Randomized controlled trials comparing PMX-DHP with conventional therapy on the outcome of mortality in patients with severe sepsis/septic shock.Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. Primary outcomes were mortality and adverse events. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate quality of evidence and grade the strength of recommendation.In seven trials enrolling 841 patients, assessment for risk of bias indicated variations in study quality from high (n = 4) to unclear (n = 3) resulting from a lack of adequate randomization, blinding, and incomplete outcomes. Polymyxin B-immobilized fiber therapy was associated with lower mortality (risk ratio, 0.65; 95% confidence interval [CI], 0.47-0.89; p = 0.007; IPolymyxin B-immobilized fiber therapy was associated with reduced mortality in sepsis/septic shock. Based on the low quality of evidence, therapeutic use of PMX-DHP for survival benefit may be recommended conditionally for patients with high risk of death. Additional large randomized controlled trials are needed to confirm or refute this evidence.

Selecting an appropriate target population is essential to maximize survival benefits of anticoagulant therapy against sepsis. Our meta-analysis of three populations with sepsis and nationwide observational study in Japan showed that anticoagulants improved mortality only in sepsis-induced disseminated intravascular coagulation (DIC) but not in non-DIC. This divergent effect was physiologically explained by host-protective immune responses of local thrombosis, which are mandatory in the early stage of sepsis. Meanwhile, the lack of definitive evidence for survival benefit provided by several trials of sepsis-induced DIC indicated that this condition was probably not the best target of anticoagulants. Our multicenter cohort study including only patients with sepsis-induced DIC showed a survival benefit from recombinant thrombomodulin only in patients with high disease severity. Thus, we believe that the population with sepsis and DIC and high disease severity is the optimal target for anticoagulant therapy. Anticoagulant therapy without appropriate target selection should be avoided because of the increased risk of bleeding with no survival benefit.

Acute respiratory distress syndrome (ARDS) remains a major cause of death. Epidemiology should be continually examined to refine therapeutic strategies for ARDS. We aimed to elucidate demographics, treatments, and outcomes of ARDS in Japan.This is a prospective cohort study for ARDS. We included adult patients admitted to intensive care units through emergency and critical care departments who satisfied the American-European Consensus Conference (AECC) acute lung injury (ALI) criteria. In addition, the fulfillment of the Berlin definition was assessed. Logistic regression analyses were used to examine the association of independent variables with outcomes.Our study included 166 patients with AECC ALI from 34 hospitals in Japan; among them, 157 (94.6%) fulfilled the Berlin definition. The proportion of patients with PaO2/FIO2 ≤ 100, patients under invasive positive pressure ventilation (IPPV), and in-hospital mortality was 39.2%, 92.2%, and 38.0% for patients with AECC ALI and 38.9%, 96.8%, and 37.6% for patients with Berlin ARDS, respectively. The area of lung infiltration was independently associated with outcomes of ARDS. Low-mid-tidal volume ventilation was performed in 75% of patients under IPPV. Glucocorticoid use was observed in 54% patients, and it was positively associated with mortality.Our study included a greater percentage of patients with ARDS with high severity and found that the overall mortality was 38%. The management of ARDS in Japan was characterized by high the utilization rate of glucocorticoids, which was positively associated with mortality.

Sepsis leads to coagulopathy by the activation of inflammatory mediators and vascular endothelial cell injury. A number of biomarkers are used to evaluate coagulopathy on sepsis. Fibrinogen and antithrombin activity have been reported as biomarkers of coagulopathy; however, the utility of these two markers has not been well established. This study aimed to evaluate the detailed association between these two markers and clinical outcomes in sepsis patients.This was a post hoc analysis of a multicenter, prospective cohort study conducted in 59 intensive care units throughout Japan from January 2016 to March 2017. We included 1103 adult patients with severe sepsis based on the Sepsis-2 criteria. The associations between the coagulation markers and in-hospital mortality were examined using linear and non-linear logistic regression analyses. We also evaluated the associations between the coagulation markers and disseminated intravascular coagulation (DIC) scores. The International Society on Thrombosis and Haemostasis overt DIC score was calculated after subtracting the fibrinogen component.The decreased levels of the fibrinogen and antithrombin activity were significantly associated with an increase in mortality (P = 0.011 and 0.002, respectively). In addition, cubic spline regression demonstrated that mortality sharply increased at a fibrinogen level of approximately200 mg/dL and at an antithrombin activity of approximately50%. Similarly, the decreased levels of the two markers non-linearly correlated with the elevation of DIC score.The fibrinogen level and antithrombin activity should be reconsidered as unique biomarkers for sepsis and sepsis-induced DIC.

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.

Background Disseminated intravascular coagulation (DIC) associated with multiple organ dysfunction syndrome (MODS) plays pivotal roles in severe sepsis. Objectives We performed a multicenter, prospective data collection study and retrospectively analyzed the data to confirm the role of DIC in severe sepsis. Methods Eligible patients were ICU patients who met the definitions of severe sepsis, and 1013 patients were included. DIC scores as well as disease severity and the development of MODS on the day of the diagnosis of severe sepsis (day 0) and at day 3 were evaluated. The primary outcome was hospital mortality, and MODS on days 0 and 3 was the secondary outcomes. Results The overall mortality rate of severe sepsis was 21.5%, and the prevalence of DIC was 50.9% (516/1013). DIC patients were more seriously ill and exhibited a higher prevalence of MODS (32.0% vs. 13.1%) on day 0 and worse mortality rate (24,8% vs. 17.5%) than non-DIC patients. DIC patients also showed a lower survival probability than non-DIC patients (Log rank p = 0.028). Logistic regression analyses after propensity score adjustment for potential confounders confirmed a significant association between DIC and MODS and hospital death in the patients with severe sepsis. The new development of DIC and persistent DIC from days 0 to 3 were associated with a high incidence of MODS and low survival probability. Conclusions The mortality rate of severe sepsis has been improved; however, DIC is still associated with the poor prognosis of these patients. Evaluating the dynamic changes in the DIC status may improve the prediction capability.

Nakao, S., Katayama, Y., Hirayama, A. et al. Trends and outcomes of blunt renal trauma management: a nationwide cohort study in Japan. World J Emerg Surg 15, 50 (2020). https://doi.org/10.1186/s13017-020-00329-w, Background: There is a paucity of information for predicting patient outcomes other than the American Association for the Surgery of Trauma (AAST) renal injury scale. The aim of this study was to evaluate the association between the patient characteristics and outcomes of patients with blunt renal trauma using a nationwide database in Japan. Methods: We performed a retrospective analysis of the Japan Trauma Data Bank (JTDB) from 2004 to 2018. We identified patients with blunt renal trauma by AIS codes converted to AAST grades. We evaluated trends in patient characteristics and management and assessed factors associated with mortality and nephrectomy using a multivariable logistic regression analysis. Results: We identified 3550 patients with blunt renal trauma. Their median age was 43 years and 74.2% were male. Nephrectomy was performed in 3.8%, and the overall mortality rate was 9.5%. We found increasing trends in age and emergency abdominal angiography and decreasing trends in nephrectomy and mortality over the 15-year period. The following factors were associated with mortality: Age ≥ 65 years (adjusted OR 3.36); pedestrian accident (adjusted OR 1.94); fall from height (adjusted OR 1.91); shock on arrival (adjusted OR 4.02); concomitant injuries to the head/neck (adjusted OR 3.14), pelvis/lower-extremity (adjusted OR 1.59), liver (adjusted OR 1.68), spleen (adjusted OR 1.45), and gastrointestinal tract (adjusted OR 1.90); AAST grades III-V (adjusted ORs 1.42, 2.16, and 5.55); and emergency abdominal angiography (adjusted OR 0.70). The following factors were associated with nephrectomy: Shock on arrival (adjusted OR 1.98), concomitant injuries to the thorax (adjusted OR 0.46) and spleen (adjusted OR 2.07), AAST grades III, IV, and V (adjusted ORs 18.40, 113.89, and 468.17), and emergency abdominal angiography (adjusted OR 0.28). Conclusions: We demonstrated that the AAST grade and emergency angiography were associated with mortality and nephrectomy in blunt renal trauma in the Japanese population.

Supplemental Digital Content is available in the text, Clinical manifestations of sepsis differ between patients with and without diabetes mellitus (DM), and these differences could influence the clinical behaviors of medical staff. Therefore, we aimed to investigate whether pre-existing DM was associated with the time to antibiotics or sepsis care protocols. This was a retrospective cohort study. It conducted at 53 intensive care units (ICUs) in Japan. Consecutive adult patients with severe sepsis admitted directly to ICUs form emergency departments from January 2016 to March 2017 were included. The primary outcome was time to antibiotics. Of the 619 eligible patients, 142 had DM and 477 did not have DM. The median times (interquartile ranges) to antibiotics in patients with and without DM were 103 minutes (60–180 minutes) and 86 minutes (45–155 minutes), respectively (P = .05). There were no significant differences in the rates of compliance with sepsis protocols or with patient-centred outcomes such as in-hospital mortality. The mortality rates of patients with and without DM were 23.9% and 21.6%, respectively (P = .55). Comparing patients with and without DM, the gamma generalized linear model-adjusted relative difference indicated that patients with DM had a delay to starting antibiotics of 26.5% (95% confidence intervals (95%CI): 4.6–52.8, P = .02). The gamma generalized linear model-adjusted relative difference with multiple imputation for missing data of sequential organ failure assessment was 19.9% (95%CI: 1.0–42.3, P = .04). The linear regression model-adjusted beta coefficient indicated that patients with DM had a delay to starting antibiotics of 29.2 minutes (95%CI: 6.8–51.7, P = .01). Logistic regression modelling showed that pre-existing DM was not associated with in-hospital mortality (odds ratio, 1.26; 95%CI: 0.72–2.19, P = .42). Pre-existing DM was associated with delayed antibiotic administration among patients with severe sepsis or septic shock; however, patient-centred outcomes and compliance with sepsis care protocols were comparable.

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.

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. Electronic supplementary material The online version of this article (10.1186/s13054-018-2186-7) contains supplementary material, which is available to authorized users.

Essentials Most anticoagulant therapy has failed to demonstrate a survival benefit in the overall sepsis population. We conducted separate meta-analyses of anticoagulant therapy in three different populations. Survival benefit was observed only in the septic disseminated intravascular coagulation (DIC) population. Further randomized controlled trials should focus on specific populations with septic DIC. SummaryBackground Although many preclinical trials have indicated the effectiveness and safety of anticoagulant therapy as an adjuvant therapy against sepsis, there is little evidence to support its effectiveness to reduce mortality in the overall population with sepsis in clinical situations. However, several studies suggested that specific anticoagulant therapy may potentially reduce mortality in patients with sepsis-induced disseminated intravascular coagulation (DIC). Objective We investigated whether the survival benefit of anticoagulant therapy might pertain to the coagulopathic population with sepsis. Methods We conducted separate meta-analyses of randomized controlled trials for anticoagulant therapy in three different populations: (i) overall population with sepsis, (ii) population with sepsis-induced coagulopathy, and (iii) population with sepsis-induced DIC. We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials comparing anticoagulant therapy with placebo or no intervention in sepsis patients. We measured all-cause mortality as the primary outcome and bleeding complications as the secondary outcome. Results We analyzed 24 trials enrolling 14 767 patients. There were no significant reductions in mortality in the overall sepsis population and the population with sepsis-induced coagulopathy. Otherwise, we observed significant reductions in mortality (risk ratio 0.72, 95% confidence interval 0.62–0.85) in the population with sepsis-induced DIC. As adverse events, bleeding complications tended to increase similarly with anticoagulant therapy in all three populations. Conclusion Although associated with an increased risk of bleeding, anticoagulant therapy resulted in no survival benefits in the overall sepsis population and even the population with sepsis-induced coagulopathy; beneficial effects on mortality were observed only in the population with sepsis-induced DIC.

Background: Current disseminated intravascular coagulation (DIC) criteria are insufficient for predicting mortality. Hemostatic endothelial molecular markers are useful for DIC diagnoses. We aimed to design new DIC criteria involving these markers based on the recently published Japanese Association for Acute Medicine (JAAM) DIC criteria, which exhibit higher sensitivity for mortality. Materials and Methods: Patients with severe sepsis or septic shock admitted to a tertiary referral hospital in Japan between September 2009 and November 2011 were included. Clinical data, including hemostatic endothelial molecular markers, were measured within 12 hours after admission. Receiver operating characteristic analyses were conducted for 8 candidate variables to identify the mortality-related markers. Then, we designed new unified criteria based on the JAAM DIC criteria and involving the identified optimal markers. Results: Of the 79 patients, 66 (83.5%) survived and 13 (16.5%) died. Protein C activity correlated best with mortality with a very high prognostic value (area under the curves [AUCs] = 0.850; P < .001), followed by plasminogen activator inhibitor 1 (AUC = 0.828; P < .001). The unified criteria, consisting of the JAAM DIC criteria plus these 2 markers, exhibited greater prognostic value for mortality (sensitivity, 84.6%; specificity, 80.3%). Moreover, DIC-positive patients using the unified criteria had significantly higher disease severity, as indicated by the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. Conclusion: Our unified criteria involving hemostatic endothelial molecular markers reflected not only mortality but also the severity of illness in patients with severe sepsis.

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. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1415-1) contains supplementary material, which is available to authorized users.