Modified abbreviated burn severity index as a predictor of in-hospital mortality in patients with inhalation injury: development and validation using independent cohorts.

PURPOSE: The ability to accurately evaluate the severity of inhalation injury can help to optimize patient care. However, there is no accepted severity grading system, especially for inhalation injury. METHODS: We screened a multicenter burn registry and included adult patients who required oxygen treatment or mechanical ventilation. After the patient data were divided into development and validation cohorts, missing values were replaced with multiple imputation. Twelve potential predictors were analyzed using multivariate logistic regression to identify prognostic variables for in-hospital mortality and scores were assigned to each predictor based on odds ratios to develop the Modified Abbreviated Burn Severity Index, mABSI. The mABSI was validated using c-statistics and calibration curves. RESULTS: We randomly assigned 1377 and 919 patients to the development and validation cohorts, respectively. Age, self-inflicted injury, cutaneous burn area, and mechanical ventilation requirement were identified as independent predictors, and the mABSI (1-17 scale) was, thus, developed. The mABSI has a high discriminatory power (c-statistic = 0.94; 95% CI 0.92-0.97), and both estimated and observed in-hospital mortalities increased from 1% at score ≤ 5 to almost 100% at score ≥ 14 with linear calibration plots. CONCLUSIONS: We developed and validated the mABSI which accurately predicts in-hospital mortality.

Effects of thrombomodulin alfa on hemostatic parameters in disseminated intravascular coagulation: Post hoc analysis of a phase 3 randomized controlled trial.

BACKGROUND: The efficacy and safety of thrombomodulin alfa (TM-α), a cofactor protein promoting thrombin-mediated protein C activation, have been examined in a phase 3 randomized, double-blinded, parallel-group trial in Japan. We have previously reported that TM-α is noninferior to heparin for the resolution of disseminated intravascular coagulation (DIC). OBJECTIVE: To investigate the basis for the efficacy of TM-α in the phase 3 clinical trial in Japan through post hoc analysis of coagulation and fibrinolysis parameters. PATIENTS/METHODS: The 227 patients of the full analysis set population described in the original phase 3 trial in Japan were included in this analysis. Changes in parameters between before and after TM-α or heparin administration in each of the two patient groups, with underlying diseases of either hematologic malignancy or infection, were studied separately and results were compared between TM-α and heparin treatment groups in a post hoc manner. RESULTS: TM-α administration did not prolong activated partial thromboplastin time but significantly decreased thrombin-antithrombin complex levels compared with heparin treatment. TM-α administration reduced consumption of endogenous anticoagulants such as antithrombin and protein C by DIC, compared with the heparin group. DIC scores were decreased in both TM-α and heparin groups during the 6-day treatment. CONCLUSION: TM-α can alleviate intravascular coagulation and consumption of anticoagulants without extending coagulation times. This may be associated with the relatively low risk of bleeding during TM-α treatment.

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.

Correlation of the Blood Test Results Obtained between Assays Using Microliter-scale Fingertip Blood Samples Collected with a Novel Blood Collection Device and Conventional Venous Blood Assays: a Secondary Publication in English.

In this study, we investigated the correlations between biochemical and hematological test results obtained using microliter-scale fingertip blood samples collected with a newly developed blood collection device and those obtained using conventional venous blood. Eighty volunteer subjects were enrolled in this study. Blood samples were drawn from the fingertip of the ring finger by a single puncture, and 60-µL samples were promptly and accurately aspirated into a blood collection chip. Then the chip was tightly sealed in a chip container and was shaken to mix the contents without dispersion. For biochemical tests other than that for HbA1c, blood was collected without anticoagulant and centrifuged to obtain 15 µL of serum which was then diluted with 190 µL of physiological saline for the assay. For hematological tests and the test for HbA1c, the sample was assayed with blood collected using EDTA-2 K. Good correlations were obtained between the test results of the assay using fingertip blood and that using venous blood. The correlation coefficients were ≥0.97 for TG, T-CHO, HDL-C, LDL-C, GLU, ALT, γ-GTP, UA, BUN, and HbA1c and ≥0.95 for WBC, RBC, Hgb, and Hct. These results suggest that our microliter-scale blood testing system is comparable to assays using venous blood and may be useful as a rapid and simple test to determine basic clinical parameters that are close to the reference intervals.

Early evaluation of severity in patients with severe sepsis: a comparison with "septic shock" - subgroup analysis of the Japanese Association for Acute Medicine Sepsis Registry (JAAM-SR).

Aim: The purpose of this subgroup analysis of a Japanese multicenter registry, the Japanese Association for Acute Medicine Sepsis Registry Advanced (JAAM-SR-Advanced), was to identify early outcome indicators for severe sepsis that are useful and more objective than "septic shock." Methods: Among 624 patients with severe sepsis registered in JAAM-SR-Advanced, 554 with valid serum lactate data were retrospectively studied. Hypotension before and after fluid resuscitation and the highest lactate values over the initial 24 h were compared for their ability to predict in-hospital mortality. Results: Of the study group, 155 (28.0%) patients were non-survivors and had significantly lower systolic blood pressures and higher lactate peaks. The mortality of 364 patients with initial hypotension was higher than those patients without it (32.7% versus 19.1%, P < 0.01). Patients with the worst lactate values ≥4 mmol/L had much higher mortality than other patients (P < 0.001). In an attempt to predict outcomes, we combined initial hypotension and the worst lactate values. The patient group with initial hypotension and the worst lactate values ≥4 mmol/L (183 patients, 33.0%) had a significantly higher mortality rate of 48.6% than the other groups (P < 0.01). Conclusion: The novel combined criterion of initial hypotension and the worst lactate values ≥4 mmol/L within the initial 24 h is potentially useful as a single outcome predictor for severe sepsis.

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.

[Correlation of the Blood Test Results Obtained Between Assays Using Microliter-Scale Fingertip Blood Samples Collected with a Novel Blood Collection Device and Conventional Venous Blood Assays].

In this study, we investigated the correlations of values of biochemical and hematological tests obtained using microliter-scale fingertip blood samples collected with a newly developed blood collection device with those using conventional venous blood. Eighty volunteer subjects were enrolled in the study. Blood sam- ples were drawn from the fingertip of the ring finger by a single puncture and 60 µL of each sample was promptly and accurately aspirated into a blood collection chip. Then the chip was tightly sealed with chip container and was shaken to mix the contents without dispersing. For biochemical tests except of HbAlc, blood was collected without anticoagulant and centrifuged to obtain 15 µL of serum which was then diluted with 190 pL of physiological saline for the assay. For hematological tests and HbAlc, the sample was as- sayed with blood collected using EDTA-2K. As a result, a good correlation of the test values was obtained between the assay with fingertip blood and that with venous blood. The correlation coefficients were found to be 0.97 in TG, T-CHO, HDL-C, LDL-C, GLU, ALT, γ-GTP, UA, BUN and HbAlc and ≥ 0.95 for WBC, RBC, Hgb, and Hct. These results suggest that our microliter-scale blood testing can be comparable to the assay using venous blood and may be useful as a rapid and simple test for determination of basic clinical tests near the reference intervals. [Original].

Cardiopulmonary Resuscitation Training in Schools: A Comparison of Trainee Satisfaction among Different Age Groups.

Cardiopulmonary resuscitation (CPR) has recently been added to the school curriculum worldwide and is currently taught to students between the ages of 10 and 16 years. The effect of the age of trainees on their satisfaction with CPR training has yet been elucidated. The aim of this study was to compare the satisfaction of trainees of different ages who participated in CPR training in schools in Japan. In total, 392 primary school students (10-11 years old), 1798 junior high school students (12-13 years old), and 4162 high schools students (15-16 years old) underwent the same 3-h course of CPR training, according to the guidelines of 2000 for Emergency Cardiovascular Care and CPR. The course was evaluated by a questionnaire completed by the participants. Primary school students responded most positively to all questions, including those reflecting enjoyment and the confidence of participants to apply CPR (Jonckheere-Terpstra test: P < 0.01). Exploratory factor analysis defined three latent variables (reaction, concentration, and naïveté) based on the seven variables addressed in the questionnaire. In the causal relationships analyzed by structural equation modeling (SEM), naïveté (which is related to age) directly affected the other latent variables. The current model suggested that the students' satisfaction with CPR training was strongly related to their age. Primary school students enjoyed CPR training more and were more confident in their ability to perform CPR than junior high and high school students were. Therefore, children aged 10-11 years may be the most appropriate candidates for the introduction of CPR training in schools.

Infection site is predictive of outcome in acute lung injury associated with severe sepsis and septic shock.

BACKGROUND AND OBJECTIVE: Sepsis is a leading cause of acute lung injury (ALI); however, the characteristics and outcome of sepsis-associated ALI are poorly understood. We aimed to elucidate factors that predict patient outcome in sepsis-associated ALI. METHODS: Secondary analysis of a multicenter, prospective, observational study was performed. RESULTS: Among 624 patients with severe sepsis and septic shock, 251 (40.2%) fulfilled the definition of American-European Consensus Conference definition of ALI. All-cause 28-day and in-hospital mortalities were 30.7% and 38.6%, respectively. More than 40% of ALI patients had neurological, cardiovascular and haematological dysfunctions or disseminated intravascular coagulation, all of which were associated with higher mortality. We report a significant correlation between infection site and mortality in patients with ALI, but not in those without ALI. The proportion of ALI was significantly higher in pulmonary sepsis; further, a complication of ALI was associated with higher mortality in sepsis from pulmonary and other sources, but not in abdominal sepsis. Among the other sepsis sites, urinary tract, central nervous system, catheter-related and undetermined foci of infection had worse outcomes when associated with ALI. None of the individual severe sepsis bundles, including fluid resuscitation and early antibiotic administration, correlated with mortality. Compliance with a set of sepsis management bundles was associated with better outcomes. CONCLUSION: In severe sepsis and septic shock, the proportion and effect on outcome was not uniform among infection sites. The infection site was predictive of outcome in patients with ALI but not in those without ALI.

Correlation between pharmacokinetic/pharmacodynamic indices and clinical outcomes in Japanese patients with skin and soft tissue infections treated with daptomycin: analysis of a phase III study.

The relationships between pharmacokinetic (PK)/pharmacodynamic (PD) indices and outcomes were investigated in patients with skin and soft tissue infection (SSTI) who received daptomycin at 4 mg/kg/day. Efficacy was evaluated in 55 patients from whom Staphylococcus aureus was isolated, with success rates of 94.5% and 69.1% for clinical and microbiological responses, respectively. The odds ratio for the relationship between the area under the day 1 concentration-time curve (AUC0-24h) to the MIC and the probability of clinical success was 1.03 (95% confidence interval [CI] 0.73-1.45), and that for the relationship for probability of microbiological success was 0.94 (95% CI 0.81-1.09). In 82 patients in the safety analysis, only 1 met the creatine phosphokinase (CPK) elevation criteria, and this patient's minimum concentration (C(min)) of plasma daptomycin was 5.37 µg/mL. No significant relationship was found between peak CPK and C(min) (Pearson's correlation coefficient -0.0452). In conclusion, no clear correlation between PK/PD indices and the probability of efficacy or safety events was demonstrated when daptomycin was administered in SSTI patients using the clinically recommended dosage of 4 mg/kg/day.

Impact of serum glucose levels on disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis.

Aim: To determine whether glycemic abnormality and pre-existing diabetes are associated with disease severity and mortality in patients with severe sepsis. Methods: Six hundred and nineteen patients with severe sepsis were grouped into four categories according to their blood glucose levels (<100, 100-199, 200-299, and ≥300 mg/dL). We compared disease severity and mortality between glycemic categories. In addition, we examined whether there was any relationship with pre-existing diabetes status. Results: There were no significant differences in disseminated intravascular coagulation, Sequential Organ Failure Assessment, or Acute Physiology and Chronic Health Evaluation II scores and mortality rates between patients with or without pre-existing diabetes. However, in patients without pre-existing diabetes, those with blood glucose level <100 mg/dL had higher disseminated intravascular coagulation, Sequential Organ Failure Assessment, and Acute Physiology and Chronic Health Evaluation II scores than those with levels of 100-299 mg/dL. In addition, those with level ≥300 mg/dL had a higher hospital mortality rate than those with levels of 100-199 mg/dL (odds ratio = 4.837). Multivariate logistic regression analysis revealed that a blood glucose level ≥300 mg/dL is an independent predictor of hospital mortality in these patients. In contrast, no significant differences among severity scores or mortality were observed in patients with pre-existing diabetes. Conclusions: In patients with severe sepsis, the impact of glycemic abnormality on disease severity and hospital mortality depends on the pre-existing diabetes status. Specifically, a blood glucose level ≥300 mg/dL may be associated with increased mortality in patients without pre-existing diabetes.

Clinical utility of the neutrophil elastase inhibitor sivelestat for the treatment of acute respiratory distress syndrome.

Acute respiratory distress syndrome is a serious condition that can arise following direct or indirect lung injury. It is heterogeneous and has a high mortality rate. Supportive care is the mainstay of treatment and there is no definitive pharmacological treatment as yet. Sivelestat is a neutrophil elastase inhibitor approved in Japan and the Republic of Korea for acute lung injury, including acute respiratory distress syndrome in patients with systemic inflammatory response syndrome. The aim of this review is to examine the clinical utility of sivelestat in different disease states, using data from nonclinical and clinical studies. In nonclinical studies, sivelestat appears to show benefit in acute lung injury without inhibiting the host immune defense in cases of infection. Clinical studies do not yet provide a clear consensus. Phase III and IV Japanese studies have shown improvements in pulmonary function, length of intensive care unit stay, and mechanical ventilation, but a non-Japanese multicenter study did not demonstrate sivelestat to have an effect on ventilator-free days or 28-day all-cause mortality. Evidence of improvement in various parameters, including duration of stay in intensive care, mechanical ventilation, the ratio of partial pressure of arterial oxygen and fraction of inspired oxygen (PaO2/FIO2 ratio) ratio, and lung injury scores, has been shown in patients with sepsis or gastric aspiration, and following the surgical treatment of esophageal cancer. To date, there are no particular concerns regarding adverse events, and the available data do not suggest that sivelestat might worsen infections. One study has analyzed cost-effectiveness, finding that sivelestat may reduce costs compared with standard care. The currently available evidence suggests that sivelestat may show some benefit in the treatment of acute lung injury/acute respiratory distress syndrome, although large, randomized controlled trials are needed in specific pathophysiological conditions to explore these potential benefits.

Epidemiology of severe sepsis in Japanese intensive care units: a prospective multicenter study.

Severe sepsis is a leading cause of morbidity and mortality in the intensive care unit (ICU). We conducted a prospective multicenter study to evaluate epidemiology and outcome of severe sepsis in Japanese ICUs. The patients were registered at 15 general critical care centers in Japanese tertiary care hospitals when diagnosed as having severe sepsis. Of 14,417 patients, 624 (4.3%) were diagnosed with severe sepsis. Demographic and clinical characteristics at enrollment (Day 1), physiologic and blood variables on Days 1 and 4, and mortality were evaluated. Mean age was 69.0 years, and initial mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 23.4 and 8.6, respectively. The 28-day mortality was 23.1%, and overall hospital mortality was 29.5%. SOFA score and disseminated intravascular coagulation (DIC) score were consistently higher in nonsurvivors than survivors on Days 1 and 4. SOFA score, DIC score on Days 1 and 4, and hospital mortality were higher in patients with than without septic shock. SOFA score on Days 1 and 4 and hospital mortality were higher in patients with than without DIC. Logistic regression analyses showed age, presence of septic shock, DIC, and cardiovascular dysfunction at enrollment to be predictors of 28-day mortality and presence of comorbidity to be an additional predictor of hospital mortality. Presence of septic shock or DIC resulted in approximately twice the mortality of patients without each factor, whereas the presence of comorbidity may be a significant predictor of delayed mortality in severe sepsis.

A multicenter, prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines.

To elucidate the standard Surviving Sepsis Campaign (SSC) guidelines-based quality of care and mortality related to severe sepsis in Japan, we conducted a multicenter, prospective, observational study using a new web-based database between June 1, 2010, and December 31, 2011. A total of 1104 patients with severe sepsis were enrolled from 39 Japanese emergency and critical care centers. All-cause hospital mortality was 29.3% in patients with severe sepsis and 40.7% in patients with septic shock. Pulmonary, renal, hepatic, and hematological dysfunctions were associated with significantly higher mortality, and hematological dysfunction, especially coagulopathy, was associated with the highest odds ratio for mortality. Compliance with severe sepsis bundles in our study was generally low compared with that in a previous international sepsis registry study, and glycemic control was associated with lowest odds ratio for mortality. Despite higher complication rates of multiple organ dysfunction syndrome and low compliance with severe sepsis bundles on the whole, mortality in our study was similar to that in the international sepsis registry study. From these results, we concluded that our prospective multicenter study was successful in evaluating SSC guidelines-based standard quality of care and mortality related to severe sepsis in Japan. Although mortality in Japan was equivalent to that reported worldwide in the above-mentioned international sepsis registry study, compliance with severe sepsis bundles was low. Thus, there is scope for improvement in the initial treatment of severe sepsis and septic shock in Japanese emergency and critical care centers.

Penetration of micafungin into the burn eschar in patients with severe burns.

Micafungin (MCFG) concentrations in the plasma and in burn eschar were investigated after daily intravenous infusion (1 h) of MCFG (200 mg) in three patients with severe burns. MCFG treatment was initiated more than 72 h after the burn injuries. The MCFG concentrations in the plasma were determined at the end of the first administration of MCFG, immediately before the second dosing, at the end of the MCFG infusion after at least 4 days from the initial treatment, and immediately before the subsequent dosing using high-performance liquid chromatography. In addition, the trough levels in burn eschar after both the initial administration and repeated administration were measured. The peak and trough levels in the plasma were comparable to or slightly lower than the reported values in healthy volunteers. The mean (range) MCFG concentrations in the burn eschar after initial administration and repeated administration were 1.41 µg/mL (<0.1-3.98 µg/mL) and 6.65 µg/mL (1.10-14.81 µg/mL), respectively. In most cases, the MCFG concentrations in the burn eschar, especially after repeated administration, were higher than the reported MIC90 of MCFG against the clinically important pathogenic species of Candida and Aspergillus. These results suggest that MCFG is capable of penetrating burn eschar.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents - Special references to bacteria isolated between April 2011 and March 2012].

Bacteria isolated from surgical infections during the period from April 2011 to March 2012 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 785 strains including 31 strains of Candida spp. were isolated from 204 (78.8%) of 259 patients with surgical infections. Five hundred and twenty three strains were isolated from primary infections, and 231 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp. and Staphylococcus spp., in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter cloacae, in this order, and from surgical site infection, E. coli was most predominantly isolated, followed by P. aeruginosa, K. pneumoniae, and E. cloacae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Collinsella aerofaciens, Lactobacillus acidophilus and Finegoldia magna, and from surgical site infection, E. lenta was most predominantly isolated, followed by P micra and L. acidophilus, in this order. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroidesfragilis was the highest from primary infections, followed by Bilophila wadsworthia, Bacteroides thetaiotaomicron, Bacteroides uniformis and Bacteroides vulgatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides caccae, B. thetaiotaomicron, Bacteroides ovatus and B. wadsworthia, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant Staphylococcus aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed. We should carefully follow up B. wadsworthia which was resistant to various antimicrobial agents, and also Bacteroides spp. which was resistant to many ß-lactams.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2010 and March 2011].

Bacteria isolated from surgical infections during the period from April 2010 to March 2011 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 631 strains including 25 strains of Candida spp. were isolated from 170 (81.7%) of 208 patients with surgical infections. Four hundred and twenty two strains were isolated from primary infections, and 184 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. such as Enterococcus faecalis, Enterococcus faecium, and Enterococcus avium was highest, followed by Streptococcus spp. such as Streptococcus anginosus and Staphylococcus spp. such as Staphylococcus aureus, in this order, from primary infections, while Enterococcus spp. such as E. faecalis and E. faecium was highest, followed by Staphylococcus spp. such as S. aureus from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Pseudomonas aeruginosa in this order, and from surgical site infection, E. coli and R aeruginosa were most predominantly isolated, followed by E. cloacae and K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rates of Parvimonas micra, Eggerthella lenta, Streptococcus constellatus, Gemella morbillorum, and Collinsella aerofaciens were the highest from primary infections, and the isolation rate from surgical site infection was generally low. Among anaerobic Gram-negative bacteria, the isolation rate of Bilophila wadsworthia was the highest from primary infections, followed by, Bacteroides fragilis and Bacteroides ovatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides thetaiotaomnicron, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant S. aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed.

The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis.

INTRODUCTION: Abnormal body temperatures (Tb) are frequently seen in patients with severe sepsis. However, the relationship between Tb abnormalities and the severity of disease is not clear. This study investigated the impact of Tb on disease severity and outcomes in patients with severe sepsis. METHODS: We enrolled 624 patients with severe sepsis and grouped them into 6 categories according to their Tb at the time of enrollment. The temperature categories (≤ 35.5 °C, 35.6-36.5 °C, 36.6-37.5 °C, 37.6-38.5 °C, 38.6-39.5 °C, ≥ 39.6 °C) were based on the temperature data of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring. We compared patient characteristics, physiological data, and mortality between groups. RESULTS: Patients with Tb of ≤ 36.5 °C had significantly worse sequential organ failure assessment (SOFA) scores when compared with patients with Tb >37.5 °C on the day of enrollment. Scores for APACHE II were also higher in patients with Tb ≤ 35.5 °C when compared with patients with Tb >36.5 °C. The 28-day and hospital mortality was significantly higher in patients with Tb ≤ 36.5 °C. The difference in mortality rate was especially noticeable when patients with Tb ≤ 35.5 °C were compared with patients who had Tb of >36.5 °C. Although mortality did not relate to Tb ranges of ≥ 37.6 °C as compared to reference range of 36.6-37.5 °C, relative risk for 28-day mortality was significantly greater in patients with 35.6-36.5 °C and ≤ 35.5 °C (odds ratio; 2.032, 3.096, respectively). When patients were divided into groups based on the presence (≤ 36.5 °C, n = 160) or absence (>36.5 °C, n = 464) of hypothermia, disseminated intravascular coagulation (DIC) as well as SOFA and APACHE II scores were significantly higher in patients with hypothermia. Patients with hypothermia had significantly higher 28-day and hospital mortality rates than those without hypothermia (38.1% vs. 17.9% and 49.4% vs. 22.6%, respectively). The presence of hypothermia was an independent predictor of 28-day mortality, and the differences between patients with and without hypothermia were observed irrespective of the presence of septic shock. CONCLUSIONS: In patients with severe sepsis, hypothermia (Tb ≤ 36.5 °C) was associated with increased mortality and organ failure, irrespective of the presence of septic shock. TRIAL REGISTRATION: UMIN-CTR ID UMIN000008195.

A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation.

OBJECTIVES: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. DESIGN: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial. SETTING: Two hundred and thirty-three ICUs in 17 countries. PATIENTS: All adult patients admitted with sepsis and suspected disseminated intravascular coagulation as assessed using a modified International Society on Thrombosis and Hemostasis score. INTERVENTIONS: Patients were randomized to receive IV ART-123 (0.06 mg/kg/d) for 6 days or placebo, in addition to standard of care. The primary endpoint was reduction in mortality. Secondary endpoints included reversal of overt disseminated intravascular coagulation and reduction in disease severity. MEASUREMENTS AND MAIN RESULTS: A total of 750 patients were randomized, nine of whom did not receive the allocated treatment so that 371 patients received ART-123 and 370 received placebo. There were no meaningful differences between the two groups in any of the baseline variables. Twenty-eight-day mortality was 17.8% in the ART-123 group and 21.6% in the placebo group (Cochran-Mantel-Haenszel two-sided p value of 0.273 in favor of ART-123, which met the predefined statistical test for evidence suggestive of efficacy). There were no statistically significant differences in event-free and alive days between the two groups. d-dimer, prothrombin fragment F1.2 and TATc concentrations were lower in the ART-123 group than in the placebo group. There were no differences between the two groups in organ function, inflammatory markers, bleeding or thrombotic events or in the development of new infections. In post hoc analyses, greatest benefit from ART-123 was seen in patients with at least one organ system dysfunction and an international normalized ratio greater than 1.4 at baseline. CONCLUSIONS: ART-123 is a safe intervention in critically ill patients with sepsis and suspected disseminated intravascular coagulation. The study provided evidence suggestive of efficacy supporting further development of this drug in sepsis-associated coagulopathy including disseminated intravascular coagulation. Future study should focus on using ART-123 in the subgroup of patients most likely to respond to this agent.

A multicenter, prospective validation study of the Japanese Association for Acute Medicine disseminated intravascular coagulation scoring system in patients with severe sepsis.

INTRODUCTION: To validate the Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scoring system in patients with severe sepsis, we conducted a multicenter, prospective study at 15 critical care centers in tertiary care hospitals. METHODS: This study included 624 severe sepsis patients. JAAM DIC was scored on the day of diagnosis of severe sepsis (day 1) and day 4. Scores for disease severity and organ dysfunction were also evaluated. RESULTS: The prevalence of JAAM DIC was 46.8% (292/624), and 21% of the DIC patients were scored according to the reduction rate of platelets. The JAAM DIC patients were more seriously ill and exhibited more severe systemic inflammation, a higher prevalence of multiple organ dysfunction syndrome (MODS) and worse outcomes than the non-DIC patients. Disease severity, systemic inflammation, MODS and the mortality rate worsened in accordance with an increased JAAM DIC score on day 1. The Kaplan-Meier curves demonstrated lower 1-year survival in the JAAM DIC patients than in those without DIC (log-rank test P<0.001). The JAAM DIC score on day 1 (odds ratio=1.282, P<0.001) and the Delta JAAM DIC score (odds ratio=0.770, P<0.001) were independent predictors of 28-day death. Dynamic changes in the JAAM DIC score from days 1 to 4 also affected prognoses. The JAAM DIC scoring system included all patients who met the International Society on Thrombosis and Haemostasis overt DIC criteria on day 1. The International Society on Thrombosis and Haemostasis scoring system missed a large number of nonsurvivors recognized by the JAAM scoring system. CONCLUSIONS: The JAAM DIC scoring system exhibits good prognostic value in predicting MODS and poor prognosis in patients with severe sepsis and can detect more patients requiring treatment. Conducting repeated daily JAAM scoring increases the ability to predict the patient's prognosis.