Pyridoxine Has a Potential to Prevent the Appearance of Pigmented Spots: Effects on the Phagocytosis and Differentiation of Keratinocytes.

Pyridoxine (VB6) is a vitamin that is essential to maintain the homeostasis of the human body by contributing to various metabolic reactions. In the skin, although some studies have shown that VB6 is involved in regulating homeostasis through the attenuation of intracellular oxidative stress, there are few reports regarding the effects of VB6 on the prevention or improvement of skin aging. Thus, we conducted this study to determine the potential anti-skin pigmentation effect of VB6 focusing on the phagocytosis of melanosomes (MSs) by keratinocytes. The phagocytosis of MSs by keratinocytes is activated by oxidative stress and is an important factor of skin pigmentation and the eventual appearance of pigmented spots. First, we confirmed the antioxidant property of VB6 that enhanced the expression of several intracellular antioxidants via nuclear erythroid factor 2-related factor 2 (Nrf2). Although the incorporation of fluorescent beads (FBs), which are used as pseudo-MSs, into keratinocytes was increased under higher oxidation conditions caused by UVB and by the depletion of intracellular glutathione, treatment with VB6 suppressed the increased incorporation of FBs into those keratinocytes via Nrf2 activation. Furthermore, VB6 restored the decreased expression of differentiation marker proteins in keratinocytes caused by FB incorporation. Taken together, the results show that VB6 has the potential to prevent the appearance of pigmented spots by suppressing the activation of phagocytosis in keratinocytes caused by oxidative stress, and by restoring the differentiation of keratinocytes disrupted by FB incorporation.

Disseminated intravascular coagulation with increased fibrinolysis during the early phase of isolated traumatic brain injury.

BACKGROUND: There is evidence to demonstrate that the coagulopathy which occurs in patients with traumatic brain injury coincides with disseminated intravascular coagulation (DIC). We hypothesized that DIC with increased fibrinolysis during the early stage of isolated traumatic brain injury (iTBI) affects the outcome of the patients and that hypoperfusion contributes to hyperfibrinolysis in the DIC. METHODS: This retrospective study included 92 patients with iTBI who were divided into DIC and non-DIC groups according to the Japanese Association Acute Medicine DIC scoring system. The DIC patients were subdivided into those with and without hyperfibrinolysis. The platelet counts and global markers of coagulation and fibrinolysis were measured. Systemic inflammatory response syndrome (SIRS), organ dysfunction (assessed by the Sequential Organ Failure Assessment score), tissue hypoperfusion (assessed by the lactate levels) and the transfusion volume were also evaluated. The outcome measure was all-cause hospital mortality. RESULTS: DIC patients showed consumption coagulopathy, lower antithrombin levels and higher fibrin/fibrinogen degradation products (FDP) and D-dimer levels than non-DIC patients. All of the DIC patients developed SIRS accompanied by organ dysfunction and required higher blood transfusion volumes, leading to a worse outcome than non-DIC patients. These changes were more prominent in DIC with hyperfibrinolysis. A higher FDP/D-dimer ratio suggests that DIC belongs to the fibrinolytic phenotype and involves fibrin(ogen)olysis. The mean blood pressures of the patients with and without DIC on arrival were identical. Hypoperfusion and the lactate levels were not identified as independent predictors of hyperfibrinolysis. CONCLUSIONS: DIC, especially DIC with hyperfibrinolysis, affects the outcome of patients with iTBI. Low blood pressure-induced tissue hypoperfusion does not contribute to hyperfibrinolysis in this type of DIC.

Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with out-of-hospital cardiac arrest.

BACKGROUND: We tested the hypothesis that disseminated intravascular coagulation (DIC) during the early phase of post-cardiopulmonary resuscitation (CPR) is associated with systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS) and affects the outcome of out-of-hospital cardiac arrest (OHCA) patients. METHODS: A review of the computer-based medical records of OHCA patients was retrospectively conducted and included 388 patients who were divided into DIC and non-DIC patients based on the Japanese Association for Acute Medicine DIC diagnostic criteria. DIC patients were subdivided into two groups: those with and without hyperfibrinolysis. Pre-hospital factors, platelet count, coagulation and fibrinolysis markers and lactate levels within 24 h after resuscitation were evaluated. The outcome measure was all-cause hospital mortality. RESULTS: DIC patients exhibited lower platelet counts, prolonged prothrombin time, decreased levels of fibrinogen and antithrombin associated with increased fibrinolysis than those without DIC. DIC patients more frequently developed SIRS and MODS, followed by worse outcomes than non-DIC patients. The same changes were observed in DIC patients with hyperfibrinolysis who showed a higher prevalence of MODS, leading to worse outcome than those without hyperfibrinolysis. Logistic regression analyses showed that lactate levels predicted hyperfibrinolysis and DIC is an independent predictor of patient death. Survival probabilities of DIC patients during hospital stay were significantly lower than non-DIC patients. The area under the receiver operating characteristic curve of DIC for the prediction of death was 0.704. CONCLUSIONS: The fibrinolytic phenotype of DIC during the early phase of post-CPR more frequently results in SIRS and MODS, especially in patients with hyperfibrinolysis, and affects the outcome of OHCA patients.

[The clinical condition and treatment of diseases associated with sudden death].

The Hokkaido Medical Society is a group of doctors and medical researchers in Hokkaido. Its purpose is to contribute to medicine and to the improvement of medical treatment. This symposium was carried out in order to inform citizens about the condition known as sudden death. We hypothesize that the incidence of sudden death tends to increase in line with the incidence of metabolic syndrome. Approximately four hundred patients were transported to our hospital by ambulance in a state of cardiopulmonary arrest (CPA) last year. The number of CPA patients who are treated in our hospital has increased in comparison to the previous decade. The theme of this year is "The clinical condition and treatment of diseases associated with sudden death" in view of the above mentioned situation. In 2015, it was reported that sudden death occurred in an American pilot and that the co-pilot was forced to make an emergency landing. Interestingly, sudden death can ever sometimes occur in pilots who undergo regular physical examinations. Numerous diseases and conditions are associated with sudden death, including: acute myocardial infarction, irregular pulse, cardiac insufficiency, cerebrovascular disease, aortic dissection and choking. We are of the opinion that the frequency of sudden death is very high in the fields of emergency medicine, cardiovascular medicine, cardiovascular surgery and neurosurgery. In this symposium, we presented and explained the condition that is known as sudden death and the current state of treatment of sudden death in emergency medicine, cardiovascular medicine, cardiovascular surgery and neurosurgery departments of the Hokkaido University Graduate School of Medicine in October, 2015. We hope that the symposium will help the citizen audience to understand the condition and treatment of sudden death, and also to help prevent sudden death.

Fibrinogen level deteriorates before other routine coagulation parameters and massive transfusion in the early phase of severe trauma: a retrospective observational study.

In trauma, hemostatic functions should be maintained appropriately to prevent massive bleeding. This study elucidated the time-dependent changes in platelet count and coagulation variables, and the effects of disseminated intravascular coagulation (DIC) on these changes during the early phase of trauma. Trauma patients with an injury severity score ≥16 were enrolled. The critical levels of platelet count and coagulation variables were defined according to recent trauma guidelines. Massive transfusion was defined as >10 units red cell concentrate. The time from arrival at the emergency department to reaching the critical levels and meeting the criteria for massive transfusion were evaluated. Eighty trauma patients were enrolled; 35 were diagnosed with DIC on arrival. Among all patients, fibrinogen levels reached the critical level earliest among routine coagulation parameters; other routine coagulation parameters deteriorated after the patients met the criteria for massive transfusion. Routine coagulation parameters reached their critical levels earlier in DIC patients than patients without DIC. Massive transfusion was performed more frequently in DIC patients, who met the criteria earlier. During the early phase of trauma, fibrinogen levels deteriorate earlier than other routine coagulation parameters, especially in DIC patients.

Rapid evaluation of fibrinogen levels using the CG02N whole blood coagulation analyzer.

Rapid evaluation of fibrinogen (Fbg) levels is essential for maintaining homeostasis in patients with massive bleeding during severe trauma and major surgery. This study evaluated the accuracy of fibrinogen levels measured by the CG02N whole blood coagulation analyzer (A&T Corporation, Kanagawa, Japan) using heparinized blood drawn for blood gas analysis (whole blood-Fbg). A total of 100 matched pairs of heparinized blood samples and citrated blood samples were simultaneously collected from patients in the intensive care unit. Whole blood-Fbg results were compared with those of citrated plasma (standard-Fbg). The whole blood coagulation analyzer measured fibrinogen levels within 2 minutes. Strong correlations between standard-Fbg and whole blood-Fbg were observed (ρ = 0.91, p < 0.001). Error grid analysis showed that 88% of the values were clinically acceptable, and 12% were in a range with possible effects on clinical decision-making; none were in a clinically dangerous range without appropriate treatment. Using a fibrinogen cutoff value of 1.5 g/L for standard-Fbg, the area under the receiver operating characteristic curve of whole blood-Fbg was 0.980 (95% confidence interval 0.951-1.000, p < 0.001). The whole blood coagulation analyzer can rapidly measure fibrinogen levels in heparinized blood and could be useful in critical care settings where excessive bleeding is a concern.

Should laryngeal tubes or masks be used for out-of-hospital cardiac arrest patients?

OBJECTIVE: Few studies have compared airway management via laryngeal masks (LM) or laryngeal tubes (LT) in patients with out-of-hospital cardiac arrest (OHCA). This study evaluated whether LT insertion by emergency medical service (EMS) personnel affected ventilation and outcomes in OHCA patients (vs. the standard LM treatment). METHODS: This prospective, cluster-randomized, and open-label study evaluated data that were collected by the Sapporo Fire Department between June 2012 and January 2013. We selected the 14 EMS teams that treated the greatest number of OHCA patients in Sapporo, Japan during 2011, and randomized the teams into Groups A and B. In the first study period (June 2012 to September 2012), Group A treated OHCA patients via LT and Group B treated OHCA patients via LM. In the second period (October 2012 to January 2013), Group A treated OHCA patients via LM and Group B treated OHCA patients via LT. If necessary, both groups were allowed to use an esophageal obturator airway (EOA) kit. The primary endpoints were time from cardiopulmonary resuscitation to device insertion and the rate of successful pre-hospital ventilation. The secondary endpoints were return of spontaneous circulation and survival and favorable neurological outcomes at 1 month after cardiac arrest. RESULTS: LT was used in 148 OHCA patients and LM was used in 165 OHCA patients. Our intention-to-treat analyses revealed no significant differences in the primary and secondary outcomes of the LT- and LM-treated groups. CONCLUSION: Prehospital advanced airway management via LT provides similar outcomes to those of LM in OHCA patients.

Trauma, shock, and disseminated intravascular coagulation: lessons from the classical literature.

A trauma patient's survival depends on the ability to control 2 opposing conditions, bleeding at the early phase and thrombosis at a late phase of trauma. The mixed existence of physiological responses for hemostasis and wound healing and pathological hemostatic responses makes it difficult to understand the mechanisms of the 2 stages of coagulopathy after trauma. Traumatic coagulopathy is multifactorial but disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype is the predominant and initiative pathogenesis of coagulopathy at the early stage of trauma. High levels of inflammatory cytokines and severe tissue injuries activate the tissue-factor-dependent coagulation pathway followed by massive thrombin generation and its activation. Low levels of protein C and antithrombin induce insufficient coagulation control and the inhibition of the anticoagulation pathway. Primary and secondary fibrin(ogen)olysis is highly activated by the shock-induced tissue hypoxia and disseminated fibrin formation, respectively. Consumption coagulopathy and severe bleeding are subsequently observed in trauma patients. Persistently high levels of plasminogen activator inhibitor-1 expressed in the platelets and endothelium then change the DIC with the fibrinolytic phenotype into the thrombotic phenotype at approximately 24 to 48 hours after the onset of trauma. All of these changes coincide with the definition of DIC, which can be clearly distinguished from normal responses for hemostasis and wound healing by using sensitive molecular markers and DIC diagnostic criteria such as those outlined by the Japanese Association for Acute Medicine and the International Society on Thrombosis and Haemostasis. Treatments of DIC with the fibrinolytic phenotype involve the surgical repair of the trauma, improvement of shock, and the rapid and sufficient replacement of platelet concentrate, fresh frozen plasma, and depleted coagulation factors. The administration of an antifibrinolytic agent (tranexamic acid) may reduce the risk of death in bleeding trauma patients associated with this type of DIC.

Dramatic changes of the gut flora immediately after severe and sudden insults.

BACKGROUND: The gut flora is crucially involved in host homeostasis. However, the changes in the gut flora during the early phase of a critical illness are unknown. AIMS: We investigated the changes in the gut flora at an early phase of severe insult in critically ill patients. METHODS: Fifteen patients who experienced a sudden and severe insult were studied, along with 12 healthy volunteers as the control group. Fecal samples were acquired from the subjects by swabs of the rectum within 6 h after admission to the emergency room (day 0). Samples were serially collected from patients until day 14. Samples were also collected from control subjects. RESULTS: On day 0, total bacterial counts were decreased to one-thousandth the number of the control subjects, in particular, obligate anaerobes and Lactobacillus were significantly decreased. In addition, on day 0, the major short-chain fatty acids of the patients were significantly lower than those of the control subjects. The gut flora and the concentrations of major short-chain fatty acids did not recover to normal levels. In contrast, Enterococcus and Pseudomonas increased during the study period. CONCLUSIONS: The gut flora in critically ill patients changed immediately after a severe insult. The concentrations of the three major short-chain fatty acids were immediately decreased in tandem with the destruction of the gut flora. The gut flora and the concentration of major short-chain fatty acids did not improve during the first 2 weeks after hospital admission. At the same time, the number of harmful bacteria gradually increased.

Clinical Features of Early Stage COVID-19 in a Primary Care Setting.

Background: The coronavirus disease 2019 (COVID-19) pandemic remains a global healthcare crisis. Nevertheless, the majority of COVID-19 cases involve mild to moderate symptoms in the early stages. The lack of information relating to these cases necessitates further investigation. Methods: Patients visiting the outpatient clinic at the Kamagaya General Hospital were screened by interview and body temperature check. After initial screening, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was suspected in 481 patients who then underwent blood tests and the loop-mediated isothermal amplification (LAMP) test for SARS-CoV-2. Clinical characteristics between positive and negative SARS-CoV-2 groups were compared. Further, the novel predictive value of routine blood test results for SARS-CoV-2 infection was evaluated using ROC analysis. Results: A total of 15,560 patients visited our hospital during the study period. After exclusion and initial screening by interview, 481 patients underwent the LAMP test and routine blood tests. Of these patients, 69 (14.3%) were positive for SARS-CoV-2 and diagnosed with COVID-19 (positive group), and 412 (85.7%) were negative (negative group). The median period between the first onset of symptoms and visit to our hospital was 3.4 and 2.9 days in the negative and positive groups, respectively. Cough (p = 0.014), rhinorrhea (p = 0.039), and taste disorders (p < 0.001) were significantly more common in the positive group, while gastrointestinal symptoms in the negative group (p = 0.043). The white blood cell count (p < 0.001), neutrophil count (p < 0.001), and percentage of neutrophils (p < 0.001) were higher in the negative group. The percentage of monocytes (p < 0.001) and the levels of ferritin (p < 0.001) were higher in the positive group. As per the predictive values for COVID-19 using blood tests, the values for the area under the curve for the neutrophil-to-monocyte ratio (NMR), white blood cell-to-hemoglobin ratio (WHR), and the product of the two (NMWH) were 0.857, 0.837, and 0.887, respectively. Conclusion: Symptoms in early stage COVID-19 patients were similar to those in previous reports. Some blood test results were not consistent with previous reports. NMR, WHR, and NMWH are novel diagnostic scores in early-stage mild-symptom COVID-19 patients in primary care settings.

[A case of brugada syndrome presenting with syncope transferred by ambulance to a neurosurgical hospital].

Brugada syndrome is a known cause of sudden death. We report a case of Brugada syndrome who was transferred by ambulance to our neurosurgical hospital. An 18-year-old male suddenly lost consciousness and collapsed at his home. His mother urgently called for an ambulance because there was atypical absence of consciousness for several minutes. Because the Japan Coma Scale (JCS) and the consciousness level was about 10 on arrival by ambulance, the emergency services suspected brain concussion, so transported him to our neurosurgical hospital. However, the JCS reached a level of 1 in the emergency room. Both skull X-P and a brain CT scan were performed but no abnormalities were observed, such as bone fracture or hematoma camed by cerebral contusion of the skull. We recognized a saddle-back ST elevation in the V3 portion and an atypical corved ST elevation in the V1-V2 portion based on the findings of electrocardiograms. As a result of the above findings, we suspected that the patient may have Brugada syndrome and the patient was therefore hospitalized and carefully followed up. We finally diagnosed the patient to have Brugada syndrome after consulting with a circulatory organ internal medicine specialist during the patient's hospitalization. Since, Brugada syndrome is a disease that may result in sudden death, further steps, such as an ICD (implantable cardioverter defibrillator) are thus considered to be necessary in this case.

Insufficient production of urinary trypsin inhibitor for neutrophil elastase release after cardiac arrest.

To investigate the relationship between the inflammatory responses and postresuscitation syndrome, we prospectively examined the serial changes of neutrophil elastase (NE), urinary trypsin inhibitor (UTI), and TNF-alpha) in successfully resuscitated patients after out-of-hospital cardiac arrest. This study included 36 patients with out-of-hospital cardiac arrests who were admitted to our intensive care unit after return of spontaneous circulation (ROSC). The 11 patients who restored to spontaneous circulation within 30 min after cardiac arrest were defined as the short cardiac arrest group. The 25 patients who restored to spontaneous circulation more than 30 min after cardiac arrest were defined as the long cardiac arrest group. Eight healthy volunteers served as control group. Daily plasma levels of NE, UTI, and TNF-alpha were measured from days 1 to 5 after ROSC. The releases of NE from activated neutrophil just after ROSC in the patients with long cardiac arrest were statistically higher than those of the short cardiac arrest group. There was a significant correlation between the NE levels and the duration of cardiac arrest. A high but insufficient production of UTI for NE release was observed on day 1, especially in the patients with a long duration of cardiac arrest. The cerebral performance category of the short cardiac arrest group was better than that of the long cardiac arrest group. Although high levels of TNF-alpha were sustained in the postresuscitation period, the levels of TNF-alpha were unrelated to the duration of cardiac arrest. In conclusion, a massive release of NE in proportion to the duration of cardiac arrest and an insufficient production of UTI for the NE release may contribute to the pathogenesis of postresuscitation syndrome after out-of-hospital cardiac arrest.

An alternative pathway for fibrinolysis is activated in patients who have undergone cardiopulmonary bypass surgery and major abdominal surgery.

INTRODUCTION: We conducted this prospective study in order to investigate the hypotheses that an alternative pathway for fibrinolysis is activated in patients who have undergone cardiopulmonary bypass (CPB) surgery and major abdominal surgery and that the levels of fibrin degradation products digested by polymorphonuclear neutrophil elastase (elastase-XDP) and the D-dimer increase in the patients' plasma. MATERIALS AND METHODS: We studied a total of 77 patients who were scheduled to undergo either CPB surgery (36 patients) or major abdominal surgery (41 patients) and then measured the elastase-XDP and D-dimer levels at several time points both during and after the surgeries. The CPB surgery was divided into surgery for aortic dissection (AD) and cardiac surgery. The major abdominal surgery consists of hepatic resection and esophagectomy. RESULTS: The elastase-XDP and D-dimer levels significantly increased in the patients who underwent both CPB surgery and major abdominal surgery. The elastase-XDP levels in AD surgery showed highest values at the end of the CPB, while the levels in the other surgeries reached their peak on the day after the surgery. Statistical difference was seen in the levels of elastase-XDP among the three subgroups undergoing a hepatic resection. While we found significant correlations between the levels of elastase-XDP and D-dimer in patients undergoing CPB surgery and a subsegmentectomy of a cirrhotic liver, the correlation coefficients were markedly low in comparison to those of the other surgeries. CONCLUSIONS: Our findings demonstrated that the elastase-mediated pathway of fibrinolysis is activated to varying degrees depending on the surgery performed. Variations in the correlation coefficients between the levels of elastase-XDP and D-dimer may suggest that elastase-mediated fibrinolysis play a different role from the physiological fibrinolysis mediated by plasmin.

The activation of neutrophil elastase-mediated fibrinolysis is not sufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation associated with systemic inflammation.

INTRODUCTION: We conducted a prospective study to test the hypothesis that the activation of neutrophil elastase-mediated fibrinolysis is insufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation (DIC) in patients associated with systemic inflammation. MATERIALS AND METHODS: We investigated 45 consecutive patients with systemic inflammatory response syndrome (SIRS) and sepsis, classified as 11 DIC and 34 non-DIC. Fibrin degradation products by neutrophil elastase (Elastase-XDP) and by plasmin (FDP), cross-linked fibrin degradation products (D-dimer), soluble fibrin, antithrombin, protein C, plasminogen activator inhibitor-1 (PAI-1), and urinary trypsin inhibitor (UTI) were measured within 24 h after the patients met either the SIRS or sepsis criteria (day 0), as well as on days 2 and 4. RESULTS: In DIC patients, higher levels of soluble fibrin, PAI-1, and FDP and markedly lower levels of antithrombin and protein C were observed in comparison to those in non-DIC patients. DIC patients showed a significantly higher level of peak Elastase-XDP than non-DIC patients (25.7+/-5.9 vs. 16.3+/-2.6 microg/mL, respectively; p=0.0333). However, we could not find any substantial difference in the levels of Elastase-XDP, UTI, and D-dimer on each day during the study period between the two groups. Good correlations were observed between the levels of D-dimer and Elastase-XDP in both patients with and without DIC (r(s)=0.699 and r(s)=0.817, respectively), but the coefficients of determination in both groups showed low values and the slopes of the regression lines were less than 1.0. A multivariate logistic regression analysis showed the elevated peak Elastase-XDP levels to inversely correlate with death. On the other hand, the DIC patients showed a higher number of organ dysfunctions and a poorer prognosis than did the non-DIC patients. CONCLUSIONS: The activation of the neutrophil elastase-mediated fibrinolytic pathway may be insufficient to overcome the fibrinolytic shutdown by PAI-1 and may in part explain the poor prognosis of DIC patients associated with systemic inflammation.

High macrophage migration inhibitory factor levels in disseminated intravascular coagulation patients with systemic inflammation.

To determine the relationship between macrophage migration inhibitory factor (MIF) and disseminated intravascular coagulation (DIC) in patients with systemic inflammatory response syndrome (SIRS) and sepsis, and their relationship to multiple organ dysfunction syndrome (MODS) and prognosis, we conducted a prospective cohort study. Forty-eight patients with SIRS or sepsis were classified as 20 DIC and 28 non-DIC patients. MIF, tumor necrosis factor-alpha (TNF-alpha), soluble fibrin, protein C activity (protein C), and plasminogen activator inhibitor-1 (PAI-1) were all measured within 24 h after the patients met the criteria of SIRS or sepsis (day 0), and on days 1 to 4. The number of SIRS criteria that the patients met and the DIC scores were determined simultaneously. In DIC patients, significantly higher levels of MIF, TNF-alpha, soluble fibrin, PAI-1 were found compared with non-DIC patients. We also found significantly lower protein C levels in the DIC patients than in the non-DIC patients. Significant correlations were found between the peak levels of MIF and soluble fibrin in the DIC patients (rs = 0.496, p < 0.0407). All DIC patients had MODS and also showed a higher number of dysfunctioning organs and a poorer prognosis than the non-DIC patients. A simple logistic regression analysis showed the peak MIF levels and DIC significantly to be related to the patients' death (odds ratio 1.016 and 40.5; p < 0.0409, p < 0.0009, respectively). In conclusion, DIC patients with elevated levels of MIF and TNF-alpha had more organ dysfunctions leading to a poor prognosis in a population of SIRS and sepsis patients. MIF may therefore play a role in the inflammatory and thrombotic processes in DIC patients.

Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients.

OBJECTIVE: This study aimed to test the hypothesis that coagulation, fibrinolytic markers and disseminated intravascular coagulation (DIC) score (International Society on Thrombosis and Haemostasis) at hospital admission of out-of-hospital cardiac arrest (OHCA) patients can predict neurological outcomes 1 month after cardiac arrest. METHODS: In this retrospective, observational analysis, data were collected from the Sapporo Utstein Registry and medical records at Hokkaido University Hospital. We included patients who experienced OHCA with successful return of spontaneous circulation (ROSC) between 2006 and 2012 and were transferred to Hokkaido University Hospital. From medical records, we collected information about the following coagulation and fibrinolytic factors at hospital admission: platelet count; prothrombin time; activated partial thromboplastin time; plasma levels of fibrinogen, D-dimer, fibrin/fibrinogen degradation products (FDP), and antithrombin; and calculated DIC score. Favorable neurological outcomes were defined as a cerebral performance category 1-2. RESULTS: We analyzed data for 315 patients. Except for fibrinogen level, all coagulation variables, fibrinolytic variables, and DIC score were associated with favorable neurological outcomes. In the receiver operating characteristic curve analysis, FDP level had the largest area under the curve (AUC; 0.795). In addition, the AUC of FDP level was larger than that of lactate level. CONCLUSIONS: All of the coagulation and fibrinolytic markers, except for fibrinogen level, and DIC score at hospital admission, were associated with favorable neurological outcomes. Of all of the variables, FDP level was most closely associated with favorable neurological outcomes in OHCA patients who successfully achieved ROSC.

Activated protein C does not increase in the early phase of trauma with disseminated intravascular coagulation: comparison with acute coagulopathy of trauma-shock.

We hypothesized that activated protein C does not increase in disseminated intravascular coagulation (DIC) after trauma and that the same is true for acute coagulopathy of trauma-shock (ACOTS). Activated protein C levels were prospectively measured in 57 trauma patients: 30 with DIC and 27 without DIC. Normal to more decreased activated protein C levels were observed in DIC patients than in the controls and non-DIC patients. The activated protein C levels in ACOTS patients were similar to those in DIC patients. In conclusion, activated protein C does not increase in either DIC or ACOTS in the early phase of trauma.

The response time threshold for predicting favourable neurological outcomes in patients with bystander-witnessed out-of-hospital cardiac arrest.

OBJECTIVE: It is well established that the period of time between a call being made to emergency medical services (EMS) and the time at which the EMS arrive at the scene (i.e. the response time) affects survival outcomes in patients who experience out-of-hospital cardiac arrest (OHCA). However, the relationship between the response time and favourable neurological outcomes remains unclear. We therefore aimed to determine a response time threshold in patients with bystander-witnessed OHCA that is associated with positive neurological outcomes and to assess the relationship between the response time and neurological outcomes in patients with OHCA. METHODS: This study was a retrospective, observational analysis of data from 204,277 episodes of bystander-witnessed OHCA between 2006 and 2012 in Japan. We used classification and regression trees (CARTs) and receiver operating characteristic (ROC) curve analyses to determine the threshold of response time associated with favourable neurological outcomes (Cerebral Performance Category 1 or 2) 1 month after cardiac arrest. RESULTS: Both CARTs and ROC analyses indicated that a threshold of 6.5min was associated with improved neurological outcomes in all bystander-witnessed OHCA events of cardiac origin. Furthermore, bystander cardiopulmonary resuscitation (CPR) prolonged the threshold of response time by 1min (up to 7.5min). The adjusted odds ratio for favourable neurological outcomes in patients with OHCA who received care within ≤6.5min was 1.935 (95% confidential interval: 1.834-2.041, P<0.001). CONCLUSIONS: A response time of ≤6.5min was closely associated with favourable neurological outcomes in all bystander-witnessed patients with OHCA. Bystander CPR prolonged the response time threshold by 1min.

Effects of prehospital epinephrine administration on neurological outcomes in patients with out-of-hospital cardiac arrest.

BACKGROUND: To determine if the effects of epinephrine administration on the outcome of out-of-hospital cardiac arrest (OHCA), patients are associated with the duration of cardiopulmonary resuscitation (CPR) performed by Emergency Medical Service (EMS) personnel. METHODS: This retrospective, nonrandomized, observational analysis used the All-Japan Utstein Registry, a prospective, nationwide population-based registry of all OHCA patients transported to the hospital by EMS staff as the data source. We stratified all OHCA patients for quartile of EMSs' CPR duration. Group 1 consisted of patients who fell under the 25th percentile of EMSs' CPR duration (under 15 min); group 2, patients who fell into the 25th to 50th percentile (between 15 and 19 min); group 3, patients who fell into the 50th to 75th percentile (between 20 and 26 min); and group 4, patients who fell at or above the 75th percentile (over 26 min). The primary endpoint was a favorable neurological outcome 1 month after cardiac arrest. The secondary endpoints were ROSC before arrival at the hospital and 1-month survival. RESULTS: A total of 383,811 patients aged over 18 years who had experienced OHCA between 2006 and 2010 in Japan, when stratified for quartile of EMSs' CPR duration, the epinephrine administration increased the rate of return of spontaneous circulation (ROSC) approximately tenfold in all groups. However, the beneficial effects of epinephrine administration on 1-month survival disappeared in patients on whom EMSs' CPR had been performed for more than 26 min, and the beneficial effects of epinephrine administration on neurological outcomes were observed only in patients on whom EMSs' CPR had been performed between 15 and 19 min (odds ratio, 1.327, 95 % confidence intervals, 1.017-1.733 P = 0.037). CONCLUSIONS: Epinephrine administration is associated with an increase of ROSC and with improvement in the neurological outcome on which EMSs' CPR duration is performed between 15 and 19 min.

Noble-Collip Drum Trauma Induces Disseminated Intravascular Coagulation But Not Acute Coagulopathy of Trauma-Shock.

BACKGROUND: There are two opposing possibilities for the main pathogenesis of trauma-induced coagulopathy: an acute coagulopathy of trauma shock and disseminated intravascular coagulation with the fibrinolytic phenotype. OBJECTIVE: The objective of this study was to clarify the main pathogenesis of trauma-induced coagulopathy using a rat model of Noble-Collip drum trauma. METHODS: Eighteen rats were divided into the control, trauma 0, and trauma 30 groups. The trauma 0 and 30 groups were exposed to Noble-Collip drum trauma. Blood samples were drawn without, immediately after, and 30 min after Noble-Collip drum trauma in the control, trauma 0, and trauma 30 groups, respectively. Coagulation and fibrinolysis markers were measured. Thrombin generation was assessed according to a calibrated automated thrombogram. RESULTS: Spontaneous thrombin bursts resulting from circulating procoagulants were observed in the nonstimulated thrombin generation assay immediately after trauma. Soluble fibrin levels (a marker of thrombin generation in the systemic circulation) were 50-fold greater in the trauma groups than in the control group. The resultant coagulation activation consumed platelets, coagulation factors, and antithrombin. Endogenous thrombin potential and factor II ratio were significantly negatively correlated with antithrombin levels, suggesting insufficient control of thrombin generation by antithrombin. High levels of active tissue-type plasminogen activator induced hyperfibrin(ogen)olysis. Soluble thrombomodulin increased significantly. However, activated protein C levels did not change. CONCLUSIONS: The systemic thrombin generation accelerated by insufficient antithrombin control leads to the consumption of platelets and coagulation factors associated with hyperfibrin(ogen)olysis. These changes are collectively termed disseminated intravascular coagulation with the fibrinolytic phenotype.