Ten-year inhospital mortality trends for patients with trauma in Japan: a multicentre observational study

Objectives: Trauma is one of the main causes of death in Japan, and treatments and prognoses of these injuries are constantly changing. We therefore aimed to investigate a 10-year trend (2004–2013) in inhospital mortality among patients with trauma in Japan.Design: Multicentre observational study.Setting: Japanese nationwide trauma registry (the Japan Trauma Data Bank) data.Participants: All patients with trauma whose Injury Severity Score (ISS) were 3 and above, who were aged 15 years or older, and whose mechanisms of injury (MOI) were blunt and penetrating between 2004 and 2013 (n=90 833).Outcome measures: A 10-year trend in inhospital mortality.Results: Inhospital mortality for all patients with trauma significantly decreased over the study decade in our Cochran-Armitage test (P<0.001). Similarly, inhospital mortality for patients with ISS 16 or more and patients who scored 50% or better on the Trauma and Injury Severity Score (TRISS) probability of survival scale significantly decreased (P<0.001). In addition, the OR for inhospital mortality of these three patient groups decreased yearly after adjusting for age, gender, MOI, ISS, Glasgow Coma Scale, systolic blood pressure and respiratory rate on hospital arrival in multivariable logistic regression analyses. Furthermore, inhospital mortality for patient with blunt trauma significantly decreased in injury mechanism-stratified Mantel-extension testing (P<0.001). Finally, multivariable logistic regression analyses showed that the OR for inhospital mortality of patients with ISS 16 and over decreased each year after adding and adjusting for means of transportation and usage of whole-body CT.Conclusion: Inhospital mortality for patients with trauma in Japan significantly decreased during the study decade after adjusting for patient characteristics, injury severity and the response environment after injury

Association of antithrombin with development of trauma-induced disseminated intravascular coagulation and outcomes

IntroductionTrauma activates the innate immune system to modulate hemostasis and minimize the damage caused by physiological bodily responses, including the activation of coagulation. Sufficiently severe trauma overwhelms physiological responses and elicits the systemic inflammatory response syndrome, which leads to the onset of disseminated intravascular coagulation (DIC), characterized by dysregulated inflammatory coagulofibrinolytic responses. Impaired anticoagulant mechanisms, including antithrombin, constitutes the pathology of DIC, while the dynamics of antithrombin and relevance to outcomes in trauma-induced coagulopathy have not been fully elucidated. This study investigated the associations of antithrombin activity with DIC onset and outcomes in severely injured patients.MethodsThis retrospective sub-analysis of a multicenter, prospective study included patients with an injury severity score ≥16. We characterized trauma patients with low antithrombin activity (antithrombin &lt;80% on hospital arrival, n = 75) in comparison with those who had normal antithrombin activity (antithrombin ≥80%, n = 200). Global markers of coagulation and fibrinolysis, molecular biomarkers for thrombin generation (soluble fibrin [SF]), and markers of anticoagulation (antithrombin) were evaluated to confirm the associations of antithrombin with DIC development and outcomes, including in-hospital mortality and the multiple organ dysfunction syndrome (MODS).ResultsPatients with low antithrombin activity had higher prevalence of shock, transfusion requirements, and in-hospital mortality. Higher DIC scores and more severe organ dysfunction were observed in the low AT group compared to that in the normal AT group. Antithrombin activity on arrival at the hospital was an independent predictor of the development of DIC in trauma patients, and levels of SF increased with lower antithrombin values (antithrombin activity &gt; 85%). Antithrombin activity at 3 h showed good predictive performance for in-hospital mortality, and a multivariable Cox proportional-hazard regression model with a cross-product term between the antithrombin and DIC showed that the in-hospital mortality in patients with DIC increased with decreased antithrombin activity. A multivariable logistic regression model showed that the odds for the development of MODS in patients with DIC increased with lower antithrombin values.ConclusionDecreased antithrombin activity in trauma-induced coagulopathy is associated with poor outcomes through worsening of DIC

Variation in the utilization of angioembolization for splenic injury in hospitals: a nationwide cross‐sectional study in Japan

Aim Substantial variations in the utilization of angioembolization have been reported internationally. However, the existence of variations in the utilization of angioembolization in Japan is currently unknown. Methods This was a cross‐sectional study using data from a nationwide trauma registry in Japan. Of the 4,896 registered adult patients with splenic injury, we investigated 3,319 patients in the top 25% of the hospitals that registered the highest number of splenic injury patients in the Japan Trauma Data Bank. The primary outcome of this study was initial angioembolization. We calculated the expected initial angioembolization rates using multiple regression analysis adjusted for patient factors. In addition, we evaluated the range of observed‐to‐expected initial splenic angioembolization ratio for each hospital. Moreover, we assessed whether this ratio was increased with time. Results The frequency of initial splenic angioembolization ranged from 0% to 52%. The median expected initial angioembolization rate, calculated through multiple logistic regression analysis, was 19.7%. The observed‐to‐expected initial splenic angioembolization ratio for each hospital ranged from 0 to 2.36. The observed initial angioembolization rate tended to increase with time (P < 0.001). Conclusions Despite adjustment for patient factors, substantial variations were observed in the utilization of splenic angioembolization among hospitals in Japan

Pioglitazone Modifies Kupffer Cell Function and Protects against Escherichia coli-Induced Bacteremia in Burned Mice

Infectious complications and subsequent sepsis in severely burned patients lead to high morbidity and mortality in response to uncontrolled innate immune responses mediated by macrophages. Peroxisome proliferator-activated receptor gamma (PPAR&gamma;) has anti-inflammatory activity and acts as a master regulator of macrophage polarization. In this study, we investigated whether the administration of a PPAR&gamma; agonist could modulate the Kupffer cell phenotype and thereby ameliorate the dysregulated innate response during post-burn bacterial infection. C57BL/6 mice were subjected to severe burns and randomized to receive either the PPAR&gamma; agonist, pioglitazone, or the vehicle control five days after injury, followed by the subsequent analysis of hepatic macrophages. Survival from the bacterial infection was monitored for seven days. Pioglitazone protected burned mice against bacterial infection. A single treatment with pioglitazone significantly enhanced phagocytosis, phagosome acidification, bacterial clearance, and reduction in inflammatory mediators in Kupffer cells. In conclusion, PPAR&gamma; activation by pioglitazone prevents clinical deterioration due to post-burn bacterial infection and improves survival. Our findings suggest that pioglitazone may be an effective therapeutic candidate for post-burn infectious complications

Effects of combination therapy using antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation

Abstract Background No single anticoagulant has been proven effective for sepsis-associated disseminated intravascular coagulation (DIC). Thus, the concomitant use of antithrombin concentrate and recombinant thrombomodulin has been conceived. This observational study was conducted to investigate the efficacy and safety of this combination therapy. Methods A total of 510 septic DIC patients who received antithrombin substitution were retrospectively analyzed. Among them, 228 were treated with antithrombin and recombinant thrombomodulin (combination therapy) and the rest were treated with antithrombin alone (monotherapy). Propensity score matching created 129 matched pairs, and 28-day all-cause mortality, DIC scores, the sequential organ failure assessment (SOFA) scores, and the incidence of bleeding were compared. Results A log-rank test revealed a significant association between combination therapy and a lower 28-day mortality rate (hazard ratio 0.49, 95% confidence interval 0.29–0.82, P = 0.006) in the matched pairs. The DIC scores and the SOFA scores in the combination therapy group were significantly lower than those in the monotherapy group on Day 4 and Day 7. The incidence of bleeding did not differ between the groups (2.11 vs. 2.31%, P = 1.000). Conclusions The current study demonstrated the potential benefit of adding recombinant thrombomodulin to antithrombin. The co-administration of these two anticoagulants was associated with reduced mortality among patients with sepsis-induced DIC without increasing the risk of bleeding

Early versus delayed vasopressor administration in patients with septic shock

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