Reevaluation of the efficacy and safety of the neutrophil elastase inhibitor, Sivelestat, for the treatment of acute lung injury associated with systemic inflammatory response syndrome; a phase IV study.

INTRODUCTION: Sivelestat, a neutrophil elastase inhibitor, has been approved in Japan for the treatment of patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome (SIRS). The Pharmaceuticals and Medical Devices Agency (PMDA) has ordered to conduct a postmarket clinical study in order to reevaluate the efficacy and safety of Sivelestat in actual clinical settings in Japan. METHODS: According to the PMDA's order, we evaluated the efficacy and safety of Sivelestat in Japanese patients with ALI associated with SIRS using ventilator-free days (VFD) as the primary endpoint. The surrogate endpoints are ventilator-weaning rate, ICU discharge rate, and 180-day survival rate. Study design was an open-label, non-randomized, multi-center clinical trial. Sivelestat was intravenously administered at 0.2 mg/kg/h continuously for a maximum of 14 days. Sivelestat group and control group were compared by adjusting the outcome values using an inverse probability of treatment weighted method based on the propensity scores. RESULTS: Four hundred and four Sivelestat group patients and 177 control group patients were enrolled. The adjusted mean number of VFD was 15.7 and 12.1 in the Sivelestat group and control group, respectively (P = 0.0022). Both the adjusted ventilator-weaning rate and ICU discharge rate were significantly higher in the Sivelestat group than in the control group (P = 0.0028 and P = 0.019, respectively). The adjusted 180-day survival rate was significantly higher in the Sivelestat group than in the control group (71.8 percent vs. 56.3 percent). CONCLUSIONS: Sivelestat contributed to early weaning from the mechanical ventilation, while showing no negative effect on the long-term outcomes of ALI associated with SIRS. The results of this study suggest the clinical usefulness of Sivelestat in this patient population.

[CPR education in Japan--past, present and future].

the last 7 years, more than 300,000 automated external defibrillators(AEDs) installed nationwide in Japan, and at least one AED has placed in 38,634 schools. Therefore, only 0.7% of bystanders used the AEDs(By-AED) in all OHCA cases with th 48 % of ROSC. In recent years, elementary and junior high school student has interested in AED results in each school has at least one AED. Therefore, introduction of CPR education starting from elementary school was extremely important. CPR education is not yet ubiquitous, and the promotion of AEDs and CPR education on a nationwide scale remains an urgent issue. Therefore, to solve this problem, we investigated the status of CPR education in schools teachers. We conducted surveys targeting for school teachers in Tokyo. Question; "What age do you think suitable for CPR training ?" Most of teachers answered"Suitable age for start CPR education from the upper grades of elementary school to a junior high school". Reason is, physically, continuous high quality chest compression could performed age of junior high. However, 'Importance of life' could teach from lower grade of elementary school because of child have a good long time memory. In this reason, CPR education is extremely important. Also teachers need 'more time', 'curriculum for CPR education and 'good CPR instruction tool for teaching'. The solution to teacher's request, we prepared follows. A 90 minutes hands only CPR curriculum should be introduced to elementary school CPR for basic CPR education. CPR +AED education should be started in lower grade of elementary school with AED trainer. In conclusion, school CPR programs are extremely important for awareness both in skill and knowledge of CPR among the entire school. Future research is warranted to improve the resuscitation rate by school CPR program.

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.

Disseminated intravascular coagulation (DIC) diagnosed based on the Japanese Association for Acute Medicine criteria is a dependent continuum to overt DIC in patients with sepsis.

INTRODUCTION: Sepsis is the most common disease associated with disseminated intravascular coagulation (DIC). To test the hypothesis that DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC scoring system (JAAM DIC) constitutes a dependent continuum to overt DIC diagnosed by the International Society on Thrombosis and Haemostasis (ISTH) overt DIC scoring system (ISTH overt DIC) in patients with sepsis, we conducted a retrospective study. MATERIALS AND METHODS: The databases from two prospective, multicenter clinical investigations were analyzed. The inclusion criteria comprised patients with sepsis-related DIC, who met the JAAM DIC criteria. RESULTS: The present study enrolled 166 patients, of whom 67 met the ISTH overt DIC criteria. All patients with sepsis who developed to overt DIC during the study period could be identified by the JAAM DIC diagnostic criteria in the first study. While the overall 28-day mortality was 31.3%, mortality (40.3%, p=0.0040) and the incidence of multiple organ dysfunction syndrome (70.1%, p=0.008) of the patients with the ISTH overt DIC was approximately one and a half times that of the patients associated with only the JAAM DIC. A stepwise increase in the ISTH overt DIC scores and the incidence of the ISTH overt DIC were also observed in accordance with the increase in the JAAM DIC scores. CONCLUSION: DIC diagnosed based on the JAAM DIC diagnostic criteria exists in a dependent continuum to the ISTH overt DIC in patients with sepsis, thus enabling them to receive early treatment.

Natural history of disseminated intravascular coagulation diagnosed based on the newly established diagnostic criteria for critically ill patients: results of a multicenter, prospective survey.

OBJECTIVE: To survey the natural history of disseminated intravascular coagulation (DIC) in patients diagnosed according to the Japanese Association for Acute Medicine (JAAM) DIC scoring system in a critical care setting. DESIGN: Prospective, multicenter study during a 4-month period. SETTING: General critical care center in a tertiary care hospital. PATIENTS: All patients were enrolled when they were diagnosed as DIC by the JAAM DIC scoring system. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Platelet counts, prothrombin time ratio, fibrinogen, and fibrin/fibrinogen degradation products were measured, and the systemic inflammatory response syndrome criteria met by the patients were determined following admission. Of 3,864 patients, 329 (8.5%) were diagnosed with DIC and the 28-day mortality rate was 21.9%, which was significantly different from that of the non-DIC patients (11.2%) (p < .0001). The progression of systemic inflammation, deterioration of organ function, and stepwise increase in incidence of the International Society on Thrombosis and Haemostasis (ISTH) DIC and its scores all correlated with an increase in the JAAM DIC score as demonstrated by the patients on day 0. There were significant differences in the JAAM DIC score and the variables adopted in the scoring system between survivors and nonsurvivors. The logistic regression analyses showed the JAAM DIC score and prothrombin time ratio on the day of DIC diagnosis to be predictors of patient outcome. The patients who simultaneously met the ISTH DIC criteria demonstrated twice the incidence of multiple organ dysfunction (61.1 vs. 30.5%, p < .0001) and mortality rate (34.4 vs. 17.2%, p = .0015) compared with those without the ISTH DIC diagnosis. CONCLUSIONS: This prospective survey demonstrated the natural history of DIC patients diagnosed by the JAAM DIC diagnostic criteria in a critical care setting. The study provides further evidence of a progression from the JAAM DIC to the ISTH overt DIC.

Clinical course and outcome of disseminated intravascular coagulation diagnosed by Japanese Association for Acute Medicine criteria. Comparison between sepsis and trauma.

The Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) study group recently announced new diagnostic criteria for DIC. These criteria have been prospectively validated and demonstrated to progress to overt DIC as defined by the International Society on Thrombosis and Haemostasis (ISTH). Although an underlying condition is essential for the development of DIC, it has never been clarified if patients with different underlying disorders have a similar course. Among 329 patients with DIC diagnosed by the JAAM criteria, those with underlying sepsis (n = 98) or trauma (n = 95) were compared. The 28-day mortality rate was significantly higher in sepsis patients than trauma patients (34.7% vs. 10.5%, p < 0.0001). Within three days of fulfilling the JAAM criteria, sepsis patients had a lower platelet count, higher prothrombin time ratio, higher systemic inflammatory response syndrome score, and higher Sequential Organ Failure Assessment score compared with trauma patients. On day 3, a significantly higher percentage of trauma patients than sepsis patients showed improvement of DIC (64.2% vs. 30.6%, p < 0.001). These differences were mainly due to patients with lower JAAM DIC scores. More than 50% of the JAAM DIC patients with sepsis who died within 28 days could not be detected by ISTH DIC criteria during the initial three days. In contrast, most trauma patients who died within 28 days had DIC simultaneously diagnosed by JAAM and ISTH criteria, except for those with brain death. These findings suggest that coagulation abnormalities, organ dysfunction, and the outcome of JAAM DIC differ between patients with sepsis and trauma.

Predictors of vascular and gastrointestinal complications in severe acute pancreatitis.

AIM: To determine prognostic factors for arterial injury and gastrointestinal perforation in patients with severe acute pancreatitis (AP). METHODS: A prospective cohort study was performed in 39 patients with AP whose Ranson scores were > or =3. The following parameters were assessed: Ranson score, APACHE II score, C-reactive protein (CRP) concentration on admission and on day 7, and contrast-enhanced computed tomography (CT) scans on admission (first CT) and between days 6 and 8 (second CT). The Balthazar CT severity index was calculated. RESULTS: Six patients developed seven vascular and/or gastrointestinal complications (duodenal perforations in 3 and arterial pseudoaneurysm in 4). CRP on day 7 and the CT severity indices at the second CT were significantly higher in the complication group than in the noncomplication group. A stepwise logistic regression analysis demonstrated that CRP > or =15 mg/dl on day 7 and CT severity index > or =7 at the second CT were independent risk factors (p = 0.02 and 0.04, respectively). The odds ratio for CRP > or =15 mg/dl was 23.0 and 15.7 for a CT severity index of > or =7. CONCLUSION: A persistent elevation of the CRP concentration and a high CT severity index are independent risk factors for local complications associated with AP.

[Influence of the diagnosis and treatment guidelines for mycosis profunda (deep mycosis) in the field of emergency and critical care medicine--with reference to patient background].

PURPOSE: This study was designed to elucidate the present situation of diagnosis and treatment for mycosis in the field of emergency and critical care medicine following presentation of the diagnosis and treatment guidelines for deep mycosis (in February, 2003). METHODS: In patients (administered antimycotics or who have pyrexia showing no response to any antimicrobial drug), medically examined and suspected of having had a fungal infection at 15 medical institutions throughout Japan, participating in the Japanese Society for the Study of Critical Care for Mycosis during the period from May 2003 through August 2004 and with facilities for emergency and critical care medicine, patient background, risk factors, contents of treatment, and patient outcomes were totaled and assessed. RESULTS: The subjects of this assessment were 125 patients consisting of 87 (69.6%) men and 38 (30.4%) women. Their mean age was 59.6 years, and 36.8% were 70 years of age or older. Intravascular catheterization was conducted in 78.4% of the 125 subjects. Antimycotics were administered to 89 patients, and the frequencies of fluconazole (FLCZ) for the initial administration and during the period of data registration were the highest (74.2% and 80.9%, respectively). The frequency with which a carbapenem antimicrobial drug was administered prior to antimycotics was the highest (41.6%). Blood culture was conducted in 85 patients (68.0%), monitoring culture in 108 (86.4%). Fungi were detected in 10 patients (11.8%) with blood culture and 72 (66.7%) with monitoring culture. The frequency of Candida albicans detection was the highest, 50.0% (5/10), with blood culture. With monitoring culture as well, the frequency of C. albicans detection was the highest, 55.6% (40/72). Alleviation of fever at the completion of registration was recognized in 65.6%. The survival rates at the completion of and at 28 days after the start of data registration of were 78.4% and 69.6%, respectively. CONCLUSION: Many patients in the field of emergency and critical care medicine had risk factors for deep mycosis; 11.8% and 66.7% of our 125 subjects were positive on blood and monitoring cultures, respectively. The majority of the fungi detected belonged to the Candida group, and FLCZ was the most frequently used antimycotic.

[Influence of the diagnosis and treatment guidelines for mycosis profunda (deep mycosis) in the field of emergency and critical care medicine--the influences of conformity and non-conformity to the guidelines on the outcomes of patients].

PURPOSE: This study was designed to investigate the influence of "The diagnosis and treatment guidelines for deep mycosis" (hereinafter referred to as "the Guidelines") in Japan on the diagnosis and treatment of deep mycosis in the field of emergency and critical care medicine and their influences on patient outcomes. METHODS: In patients (administered antimycotics or who had pyrexia showing no response to any antimicrobial drug) medically examined and suspected of having had a fungal infection at 15 medical institutions throughout Japan, participating in the Japanese Society for the Study of Critical Care for Mycosis during the period from May 2003 through August 2004 and with facilities for emergency and critical care medicine, patient background, risk factors, awareness of the Guidelines, diagnosis, contents of treatment, and outcomes were investigated. On the basis of the data pertaining to these items, whether or not the course of diagnosis and treatment for each patient conformed to the diagnosis and treatment recommended in the Guidelines was retrospectively evaluated. Whether or not the treatment had been conducted with antimycotics and the doses recommended in the Guidelines, was also investigated, and outcomes were assessed according to conformity and non-conformity to the Guidelines. RESULTS: Of the 125 subjects assessed, 55.2% responded that they were conscious of the Guidelines. The subjects who had indications for the Guidelines included 10 (8.0%), who were definitely diagnosed as having had mycosis, 3 (2.4%) who were diagnosed as having had clinical mycosis, and 35 (28.0%) who were suspected of having had mycosis. In the remaining 77 (61.6%), whether their conditions were non-mycosis or mycosis could not be determined. The treatment conformed to the Guidelines in 25 subjects (20.0%), but did not in 23 (18.4%). In 77 subjects (61.6%), whether or not the condition had been mycosis could not be determined. The number of the patients in whom whether or not the treatment had conformed to the Guidelines could be determined was decreased and there was a marked influence of administration of antimycotics, which was based on the assumption that "pyrexia with no response to broad-spectrum antimicrobial drugs persists for at least 3 days" in the Guidelines, was given as the reason. There was no significant difference in outcomes (survival or death) at the end of the study based on whether or not the subject had been conscious of the Guidelines or whether or not the contents of treatment conformed to the Guidelines. The number of days that treatment was administered in the ICU was greater in the treatment conforming to the Guidelines than in that not conforming to the Guidelines, but the difference did not reach statistical significance. CONCLUSION: The Guidelines were recognized at the time of treatment by more than half of the patients registered, but there were actually only a few patients in whom the diagnosis and treatment conformed to the Guidelines. One possible reason is considered to be that there was a marked influence of one item of the Guidelines, i.e. "pyrexia without response to broad-spectrum antimicrobial drugs persists for at least 3 days", in patients with suspected mycosis, who receive empirical treatment, in terms of the reason. Future examination is considered to be needed regarding the validity of this item.

SIRS-associated coagulopathy and organ dysfunction in critically ill patients with thrombocytopenia.

BACKGROUND: Coagulopathy and thrombocytopenia often occur in critically ill patients, and disseminated intravascular coagulation (DIC) can lead to multiple organ dysfunction and a poor outcome. However, the relation between coagulopathy and systemic inflammatory response has not been thoroughly clarified. Thus, we evaluated coagulative activity, organ dysfunction, and systemic inflammatory response syndrome (SIRS) in critically ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation. PATIENTS AND METHODS: Two hundred seventy-three patients, who were admitted to 13 critical care centers in Japan and fulfilled the criteria of platelet count of less than 150*10(9)/L, were included. Coagulative variables (platelet count, fibrin/fibrinogen degradation products, and DIC scores), organ dysfunction index (Sequential Organ Failure Assessment [SOFA] score), and SIRS score in each patient were evaluated for 4 consecutive days after fulfilling the above entry criteria. The effect of SIRS on coagulopathy and organ dysfunction was evaluated in these patients. RESULTS: Both the maximum SIRS score and entry SIRS score had significant relation to the maximum SOFA score during the observation period. Coagulation disorders indicated by the minimum platelet count, maximum DIC scores, and positivity for DIC worsened gradually with increases in SIRS scores. Both the minimum platelet count and maximum DIC scores were significantly correlated with the maximum SOFA score, indicating that a relation exists between coagulopathy and organ dysfunction. CONCLUSIONS: In critically ill patients with thrombocytopenia, coagulopathy and organ dysfunction progress with significant mutual correlation, depending on the increase in SIRS scores. The SIRS-associated coagulopathy may play a critical role in inducing organ dysfunction after severe insult.

Predicting the severity of systemic inflammatory response syndrome (SIRS)-associated coagulopathy with hemostatic molecular markers and vascular endothelial injury markers.

INTRODUCTION: The changes in biomarkers of coagulation or fibrinolysis, anticoagulation, inflammation, and endothelial damage occur in patients with systemic inflammatory response syndrome (SIRS). The purpose of this study is to assess the prognostic value of these markers in patients with SIRS-associated hypercoagulopathy. METHODS: Sixty-six SIRS patients with a platelet count less than 15.0 x 10(4)/mm3 in three university hospital intensive care units were enrolled in this prospective, comparative study. Blood samples were obtained on day 0 and day 2. Twelve hemostatic, inflammatory, and vascular endothelial indices were measured and the data were compared between the severe group (patients with a total maximum Sequential Organ Failure Assessment score of 10 or more and nonsurvivors; n = 25) and the less-severe group (Sequential Organ Failure Assessment score <10; n = 41). RESULTS: Significant changes between the groups were observed in platelet count, fibrin or fibrinogen degradation products, interleukin-6, soluble thrombomodulin, antithrombin (AT) activity, and protein C activity, both on day 0 and on day 2. In contrast, the d-dimer, soluble fibrin, plasmin-[alpha]2-antiplasmin complex, and E-selectin levels were higher in the severe group only on day 2. No significant difference was seen regarding the thrombin-AT complex and total plasminogen activator inhibitor on both days. A comparison of the areas under the receiver operating characteristic curve revealed the AT activity to be the best predictor of a progression of organ dysfunction. CONCLUSION: The changes in some hemostatic molecular markers and vascular endothelial markers were conspicuous in patients with organ dysfunction. The AT activity is considered to be the most useful predictor of organ dysfunction.

The therapeutic efficacy of edaravone in extensively burned rats.

BACKGROUND: Extensive burn injury leads to production of free radicals subsequent to massive fluid resuscitation, which in turn increases the risk of acute lung injury. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger, is clinically effective in improving the prognosis after cerebral infarction. However, the effect of edaravone against extensive burn injury has not been tested. Objected To evaluate whether edaravone can reduce free radical precursors in a 30% burn model in rats. DESIGN: Prospective, randomized controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats weighing 200 to 220 g. MAIN OUTCOME MEASURES: All rats (n = 10) were given a 30% full-thickness burn according to the Walker and Mason method. Immediately after the burn, edaravone was injected into the rats (n = 5) intraperitoneally at a dose of 9 mg/kg. One hour after burn injury, blood and tissue samples were collected to analyze free radical changes of serum and tissue malondialdehyde (MDA) and xanthine oxidase (XOD) and lung white blood cells. RESULTS: Statistical significance was found between nontreatment and edaravone treatment relative to serum MDA (mean +/- SD, 2.50 +/- 0.54 vs 1.74 +/- 0.29 nmol/mL), serum XOD (mean +/- SD, 5.04 +/- 1.67 vs 2.26 +/- 0.83 U/L), tissue MDA (mean +/- SD, 1268.7 +/- 289.9 vs 569.1 +/- 135.9 nmol/mg protein), tissue XOD (mean +/- SD, 256.3 +/- 58.1 vs 50.96 +/- 19.60 mU/g tissue), lung white blood cells (mean +/- SD, 3088 +/- 1144 vs 1542 +/- 575 mU/g tissue), and lung XOD (mean +/- SD, 428.3 +/- 210.5 vs 81.8 +/- 36.0 nmol/mg protein). CONCLUSIONS: Edaravone treatment induces significant reduction of free radical precursors and their metabolites compared with controls in burn rats. This suggests that edaravone could be helpful in the clinical treatment of large burns.

Aggressive endoscopic hemostasis for severe gastrointestinal bleeding in critically ill patients to decrease mortality.

BACKGROUND/AIMS: In critically ill patients, with gastrointestinal (GI) bleeding achieving endoscopic hemostasis has been reported to be often difficult, with a high rebleeding rate. The purpose of this study was to examine the efficacy of endoscopic hemoclipping for severe GI bleeding in critically ill patients. METHODOLOGY: This prospective study was performed at the Department of Traumatology and Critical Care Medicine, Kyorin University Hospital from June 1996 to December 1999. Patients with predefined clinically significant GI bleeding were treated using an established endoscopic hemoclipping protocol that covered indications and procedures. RESULTS: A total of 1429 patients were enrolled in this study. Of 11 hospitalized cases meeting the definition of severe GI bleeding, it occurred at 12.3 +/- 3.9 days (mean +/- SD) after admission. Initial hemostasis was possible in all patients. Although rebleeding was seen in 1 patient, the permanent hemostasis rate by additional endoscopic hemostasis was 100%. Of the 11, 9 patients were discharged and there were 2 hospital deaths. The direct cause of death depended on the degree of underlying critical illness and combined severe pneumonia. Complications caused by endoscopic hemostasis were not seen in any patient. CONCLUSIONS: Endoscopic hemostasis is useful in critically ill patients with the severe GI bleeding that occurs during critical care in the intensive care unit.

Evaluation of out-of-hospital cardiopulmonary resuscitation with resuscitative drugs: a prospective comparative study in Japan.

OBJECTIVE: This study aimed at evaluating two emergency medical service systems, one in which emergency life-saving technicians (ELSTs) are allowed to administer epinephrine (adrenaline) to patients with out-of-hospital cardiac arrest and one in which ELSTs are allowed to administer epinephrine, lidocaine, and atropine. METHODS: A modified, prospective community health trial was conducted from April 1 to October 31, 2003. Areas served by physician-manned ambulances, where out-of-hospital cardiopulmonary resuscitation (CPR) was performed with resuscitative drugs (experimental areas), were compared to areas served by ELST-manned ambulances, where resuscitative drugs were not administered outside the hospital (reference areas). The sequence of emergency procedures performed in the experimental areas was divided into three phases. Phase I included administration of epinephrine, which simulated administration of epinephrine by ELSTs. Phase II started with the use of lidocaine or atropine. Phases I and II simulated administration of epinephrine, lidocaine, and atropine by ELSTs. Phase III began with administration of another drug. Outcomes, resuscitation rates and 1-month survival rates were determined, and differences between the two types of areas were analyzed. RESULTS: For non-traumatic cardiac arrest, outcomes through phase II in the experimental areas were significantly better than those in the reference areas. Phase I-only outcomes in the experimental areas were better, but not significantly better, than those in the reference areas. CONCLUSION: Use of resuscitative drugs for non-traumatic prehospital CPR appears to be effective in terms of resuscitation rates and 1-month survival rates.

Development of a tissue-engineered human oral mucosa equivalent based on an acellular allogeneic dermal matrix: a preliminary report of clinical application to burn wounds.

Tissue-engineered skin equivalents composed of epidermal and dermal components have been widely investigated for coverage of full-thickness skin defects. We developed a tissue-engineered oral mucosa equivalent based on an acellular allogeneic dermal matrix and investigated its characteristics. We also tried and assessed its preliminary clinical application. Human oral mucosal keratinocytes were separated from a piece of oral mucosa and cultured in a chemically-defined medium. The keratinocytes were seeded on to the acellular allogeneic dermal matrix and cultured. Histologically, the mucosa equivalent had a well-stratified epithelial layer. Immunohistochemical study showed that it was similar to normal oral mucosa. We applied this equivalent in one case with an extensive burn wound. The equivalent was transplanted three weeks after the harvest of the patient's oral mucosa and about 30% of the graft finally survived. We conclude that this new oral mucosa equivalent could become a therapeutic option for the treatment of extensive burns.

An outcome study of out-of-hospital cardiac arrest using the Utstein template--a Japanese experience.

Publication of the Utstein style template has made it possible to evaluate and compare national, regional, and hospital based Emergency Medical Services. This research was a national investigation to present outcome data for out-of-hospital cardiac arrest (OHCA) patients in Japan. 3029 OHCA patients who were transported to 10 Emergency and Critical Care Medical Center from November 1997 to April 1999 were recorded according to the Utstein style and the outcome evaluated by logistic regression analysis. Among 3029 OHCA patients, 109 were found dead. The remaining 2920 patients who underwent cardiopulmonary resuscitation (CPR) by emergency medical technicians (EMT) were included in this study. Among these patients, 1294 were considered of primary cardiac origin patients by the EMT and 722 of these patients suffered a witnessed cardiac arrest. Bystander CPR were performed in 28.4% of these witnessed patients and the discharge rate was 3.5% overall and 11.4% in witnessed VF/VT. Outcome analysis showed that a discharge rate in witnessed primary cardiac arrest was 30% in prehospital resuscitation which was 7.5 times higher than in-hospital emergency room resuscitation groups (4.0%). The longer the interval between an emergency telephone call and defibrillation, the lower the 1 month survival rate, which reached almost 0% at 30 min. Follow up evaluation after discharge revealed that the survival rate rapidly decreased from 24 h to 3 months, then became a plateau in primary cardiac patients was rapidly decreased from 24 h to 1 month, then became a near plateau in non-cardiac origin group. To improve the resuscitation rate in the prehospital phase, a prehospital medical control system should be developed with expansion of on scene techniques by Japanese paramedics such as tracheal intubation, administration of emergency drugs and early defibrillation with standing orders. Education and motivation of first responders will be needed and every effort should be concentrated on improving bystander CPR rate.

[Postgraduate trauma education for surgeon--from the veiwpoint of trauma and emergency physicians].

A recent important topic in the field of trauma care is the elimination of "preventable death." Since patients' satisfactory prognosis and good recovery mainly depend upon the success of the initial evaluation and care, the responsibility of physicians who first come into contact with trauma patients in the emergency room is especially heavy. Many general surgeons examine trauma patients, although, unfortunately they have few opportunities for training in how to deal with those patients in the present educational program. Traumatology should be one of the most important areas of surgery, and therefore this paper emphasizes that every surgeon needs to be educated and trained in an adequate curriculum of trauma care. The Japanese Association for Acute Medicine could help by offering the Japan Advanced Trauma Evaluation and Care (JATEC) training program. JATEC proposes standardized guidelines as well as a nationwide the educational program for trauma management.

Thrombomodulin alfa in the treatment of infectious patients complicated by disseminated intravascular coagulation: subanalysis from the phase 3 trial.

To investigate treatment effects of thrombomodulin alfa (TM-α) in patients with disseminated intravascular coagulation (DIC) having infection as the underlying disease, retrospective subanalysis of a double-blind, randomized controlled phase 3 trial was conducted. In the phase 3 trial, 227 DIC patients (full-analysis set) having infection and/or hematologic malignancy as the underlying disease received either TM-α (0.06 mg·kg for 30 min once daily) or heparin (8 U·kg·h for 24 h) for 6 days using the double-dummy method. Among these patients, 147 patients with noninfectious comorbidity leading to severe thrombocytopenia (e.g., hematologic malignancy, or aplastic anemia) were excluded from the present analysis, and 80 patients with infectious disease and DIC were extracted and subjected to the present retrospective subanalysis. Disseminated intravascular coagulation resolution rates were determined using the DIC diagnostic criteria for critically ill patients at 7 days, and mortality rates were evaluated at 28 days. In the TM-α and heparin groups, DIC resolution rates were 67.5% (27/40) and 55.6% (20/36), and 28-day mortality rates were 21.4% (9/42) and 31.6% (12/38), respectively. Mortality rates of patients who recovered from DIC were 3.7% (1/27) in the TM-α group and 15% (3/20) in the heparin group. These results suggest TM-α may be valuable in the treatment of DIC associated with infection.