Taro Irisawa

Impact of transport to critical care medical centers on outcomes after out-of-hospital cardiac arrest ,

BACKGROUND Post-resuscitation care has emerged as an important predictor of survival from out-of-hospital cardiac arrest (OHCA). In Japan, selected hospitals are certified as Critical Care Medical Centers (CCMCs) based on their ability and expertise. HYPOTHESIS Outcome after OHCA is better in patients transported to a CCMC compared a non-critical care hospital (NCCH). MATERIALS AND METHODS Adults with OHCA of presumed cardiac etiology, treated by emergency medical services systems, and transported in Osaka from January 1, 2005 to December 31, 2007 were registered using a prospective Utstein style population cohort database. Primary outcome measure was 1 month neurologically favorable survival (CPC< or =2). Outcomes of patients transported to CCMC were compared with patients transported to NCCH using multiple logistic regressions and stratified on the basis of stratified field ROSC. RESULTS 10,383 cases were transported. Of these, 2881 were transported to CCMC and 7502 to NCCH. Neurologically favorable 1-month survival was greater in the CCMC group [6.7% versus 2.8%, P<0.001]. Among patients who were transported to hospital without field ROSC, neurologically favorable outcome was greater in the CCMC group than the NCCH group [1.7% versus 0.5%; adjusted odds ratio (OR), 3.39; 95% confidence interval (CI), 2.17-5.29; P<0.001]. In the presence of field ROSC, survival was similar between the groups [43% versus 41%; adjusted OR, 1.09; 95% CI, 0.82-1.45; P=0.554]. CONCLUSIONS Survival after OHCA of presumed cardiac etiology transported to CCMCs was better than those transported to NCCHs. For OHCA patients without field ROSC, transport to a CCMC was an independent predictor for a good neurological outcome.

Presence of Neutrophil Extracellular Traps and Citrullinated Histone H3 in the Bloodstream of Critically Ill Patients

Neutrophil extracellular traps (NETs), a newly identified immune mechanism, are induced by inflammatory stimuli. Modification by citrullination of histone H3 is thought to be involved in the in vitro formation of NETs. The purposes of this study were to evaluate whether NETs and citrullinated histone H3 (Cit-H3) are present in the bloodstream of critically ill patients and to identify correlations with clinical and biological parameters. Blood samples were collected from intubated patients at the time of ICU admission from April to June 2011. To identify NETs, DNA and histone H3 were visualized simultaneously by immunofluorescence in blood smears. Cit-H3 was detected using a specific antibody. We assessed relationships of the presence of NETs and Cit-H3 with the existence of bacteria in tracheal aspirate, SIRS, diagnosis, WBC count, and concentrations of IL-8, TNF-α, cf-DNA, lactate, and HMGB1. Forty-nine patients were included. The median of age was 66.0 (IQR: 52.5–76.0) years. The diagnoses included trauma (7, 14.3%), infection (14, 28.6%), resuscitation from cardiopulmonary arrest (8, 16.3%), acute poisoning (4, 8.1%), heart disease (4, 8.1%), brain stroke (8, 16.3%), heat stroke (2, 4.1%), and others (2, 4.1%). We identified NETs in 5 patients and Cit-H3 in 11 patients. NETs and/or Cit-H3 were observed more frequently in “the presence of bacteria in tracheal aspirate” group (11/22, 50.0%) than in “the absence of bacteria in tracheal aspirate” group (4/27, 14.8%) (p<.01). Multiple logistic regression analysis showed that only the presence of bacteria in tracheal aspirate was significantly associated with the presence of NETs and/or Cit-H3. The presence of bacteria in tracheal aspirate may be one important factor associated with NET formation. NETs may play a pivotal role in the biological defense against the dissemination of pathogens from the respiratory tract to the bloodstream in potentially infected patients.

Profile of gene expression in the subventricular zone after traumatic brain injury.

Neural stem cells, which reside in the subventricular zone (SVZ) and dentate gyrus (DG) of adult mammals, give rise to new neurons throughout life. However, these neural stem cells do not appear to contribute to regeneration in the damaged central nervous system. Following traumatic brain injury (TBI) in adult rats, the number of proliferating cells labeled with bromodeoxyuridine (BrdU) is significantly increased in the bilateral SVZ and DG; however, these proliferating cells do not contribute to effective regeneration in the damaged area. To gain insight into the molecular mechanisms of these biological actions, changes in gene expression in the SVZ after brain trauma were examined by cDNA microarray. Of 9,596 genes screened, 97 were upregulated and 204 were downregulated. Classifying these genes according to their function suggests that TBI affects a broad range of cellular functions. The validity of the data was confirmed by RT-PCR. The expression of some genes localized in the SVZ was confirmed by in situ hybridization. This combined strategy is effective for comprehensive analysis of the pathophysiological changes in the SVZ after brain injury and should contribute to the understanding of the molecular events that occur after injury. In the future, this may enable regeneration of the damaged central nervous system.

Acute Cerebral Blood Flow Variations after Human Cardiac Arrest Assessed by Stable Xenon Enhanced Computed Tomography

In this study, changes in cerebral blood flow (CBF) during acute phase after cardiopulmonary arrest (CPA) were examined in patients using stable Xenon enhanced computed tomography (Xe-CT). All patients (8) were stabilized hemodynamically within 4 hours after admission, and Xe-CT was performed immediately after restoration of spontaneous circulation (ROSC) at 8, 24, 48, 96 and 168 hours after ROSC. The progress of patients was monitored in other hospitals and clinics after discharge. Neurological outcomes were evaluated using the Glasgow outcome scale (GOS) 6 months after admission, and scores were compared against changes in CBF. Patients were grouped by prognosis. Four patients belonged to Group A (good recovery) and Group B (2 severely disabled, 2 in persistent vegetative state). The pattern of change in CBF after ROSC was found to be significantly different between Groups A and B (p <0.05). The CBF ratio relative to normal controls was higher in Group B than Group A within 48 hours after ROSC. However, at 48, 96, and 168 hours after ROSC, the opposite was observed: The CBF ratio was significantly higher in Group A than Group B (p<0.05). Based on these results, we concluded that CBF in the patients who survived after CPA changed remarkable especially within the first week. Furthermore, patients with abnormally low CBF that returns to supernormal within the first 48 hours following CPA can be expected to recover well neurologically.

Identification of neutrophil extracellular traps in the blood of patients with systemic inflammatory response syndrome.

Objective Neutrophils are able to form ‘neutrophil extracellular traps’ (NETs), which they use to trap and kill pathogens such as bacteria and fungi at the foci of infection. This observational study investigated the presence of NETs in the blood from critically ill patients and healthy volunteers. Methods Fluorescent triple-colour immunocytochemical analysis of blood smears collected from patients with systemic inflammatory response syndrome (SIRS; associated with various clinical conditions) who had been hospitalized in the intensive care unit, and healthy volunteers, was undertaken to identify NETs in the blood. Blood smears were stained for DNA, histone H1 and neutrophil elastase. Results NETs were identified in 10 of 21 (47.6%) blood samples from the study group compared with none of the blood samples from eight healthy volunteers. Conclusion These data suggest that fluorescent triple-colour immunocytochemical staining of NETs in the blood could be used to simplify the early identification of critically ill patients with SIRS. Larger studies are required to clarify the pathophysiological role of NETs in this specific patient population.

Neutrophil extracellular traps in bronchial aspirates: a quantitative analysis

Neutrophil extracellular traps (NETs) are structures composed of DNA and granular proteins, which rapidly trap and kill pathogens. The formation of NETs has been detected during infection in animal experiments, but their role in humans is unclear. The purposes of this study were to quantitatively evaluate the production of NETs during acute respiratory infection and to study the relationship between the NET length and various inflammatory mediators. We examined bronchial aspirates collected from nine intubated patients in an intensive care unit. Samples were collected at the onset of acute respiratory infection (day 0) and on days 1, 3–5, and 6–8. The NET length was visualised by immunohistochemistry and quantified using computer tracing software. The NET length was measured and compared at each time point. The length differed significantly between time points (p<0.001). NETs were significantly longer on day 1 than on day 0 (p<0.001). Neutrophils released NETs abundantly in response to respiratory infection and regression analysis showed that NET length correlated with six clinical parameters (white blood cells, platelets, lactate, CXC ligand-2, interleukin-8, and procalcitonin) as the explanatory variables. NETs in bronchial aspirates may reflect disease progression of respiratory infections. Quantification of NETs in bronchial aspirates may provide a new indicator of inflammation. NET length increases with respiratory inflammation which correlates with progression of infections http://ow.ly/sPbEX

Case of invasive nontypable Haemophilus influenzae respiratory tract infection with a large quantity of neutrophil extracellular traps in sputum.

Haemophilus influenzae type b was once the most common cause of invasive H. influenzae infection, but the incidence of this disease has decreased markedly with introduction of conjugate vaccines to prevent the disease. In contrast, the incidence of invasive infection caused by nontypable H. influenzae has increased in the US and in European countries. Neutrophil extracellular traps (NETs) are fibrous structures released extracellularly from activated neutrophils during inflammation, including in pneumonia, and rapidly trap and kill pathogens as a first line of immunological defense. However, their function and pathological role have not been fully investigated. Here, we report a case of fatal nontypable H. influenzae infection with severe pneumonia and bacteremia in an adult found to have a vast amount of NETs in his sputum. The patient had a two-day history of common cold-like symptoms and was taken to the emergency room as a cardiopulmonary arrest. He recovered temporarily, but died soon afterwards, although appropriate antibiotic therapy and general management had been instituted. Massive lobular pneumonia and sepsis due to nontypable H. influenzae was found, in spite of H. influenzae type b vaccine being available. His sputum showed numerous bacteria phagocytosed by neutrophils, and immunohistological staining indicated a number of NETs containing DNA, histone H3, and neutrophil elastase. This case highlights an association between formation of NETs and severe respiratory and septic infection. An increase in severe nontypable H. influenzae disease can be expected as a result of “pathogen shift” due to increased use of the H. influenzae type b vaccine in Japan.

Chest compression release velocity: Association with survival and favorable neurologic outcome after out-of-hospital cardiac arrest

PURPOSE We evaluated the association between chest compression release velocity (CCRV) and outcomes after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS CPR quality was measured using a defibrillator with accelerometer-based technology (E Series, ZOLL Medical) during OHCA resuscitations by 2 EMS agencies in Arizona between 10/2008 and 06/2013. All non-EMS-witnessed adult (≥ 18 years) arrests of presumed cardiac etiology were included. The association between mean CCRV (assessed as an appropriate measure of central tendency) and both survival to hospital discharge and neurologic outcome (Cerebral Performance Category score = 1 or 2) was analyzed using multivariable logistic regression to control for known and potential confounders and multiple imputation to account for missing data. RESULTS 981 OHCAs (median age 68 years, 65% male, 11% survival to discharge) were analyzed with 232 (24%) missing CPR quality data. All-rhythms survival varied significantly with CCRV [fast (≥ 400 mm/s) = 18/79 (23%); moderate (300-399.9 mm/s) = 50/416 (12%); slow (<300 mm/s) 17/255 (7%); p < 0.001], as did favorable neurologic outcome [fast = 14/79 (18%); moderate = 43/415 (10%); slow = 11/255 (4%); p < 0.001]. Fast CCRV was associated with increased survival compared to slow [adjusted odds ratio (aOR) 4.17 (95% CI: 1.61, 10.82) and moderate CCRV [aOR 3.08 (1.39, 6.83)]. Fast CCRV was also associated with improved favorable neurologic outcome compared to slow [4.51 (1.57, 12.98)]. There was a 5.2% increase in the adjusted odds of survival for each 10mm/s increase in CCRV [aOR 1.052 (1.001, 1.105)]. CONCLUSION CCRV was independently associated with improved survival and favorable neurologic outcome at hospital discharge after adult OHCA.

Duration of Coma in Out-of-Hospital Cardiac Arrest Survivors Treated With Targeted Temperature Management.

Study objective: We evaluate the time to awakening after out‐of‐hospital cardiac arrest in patients treated with targeted temperature management and determine whether there was an association with any patient or event characteristics. Methods: This was a prospective, observational cohort study of consecutive adult survivors of out‐of‐hospital cardiac arrest of presumed cardiac cause who were treated with targeted temperature management between January 1, 2008, and March 31, 2014. Data were obtained from hospitals and emergency medical services agencies responding to approximately 90% of Arizonas population as part of a state‐sponsored out‐of‐hospital cardiac arrest quality improvement initiative. Results: Among 573 out‐of‐hospital cardiac arrest patients who completed targeted temperature management, 316 became responsive, 60 (19.0%) of whom woke up at least 48 hours after rewarming. Eight patients (2.5%) became responsive more than 7 days after rewarming, 6 of whom were discharged with a good Cerebral Performance Category score (1 or 2). There were no differences in standard Utstein variables between the early and late awakeners. The early awakeners were more likely to be discharged with a good Cerebral Performance Category score (odds ratio 2.93; 95% confidence interval 1.09 to 7.93). Conclusion: We found that a substantial proportion of adult out‐of‐hospital cardiac arrest survivors treated with targeted temperature management became responsive greater than 48 hours after rewarming, with a resultant good neurologic outcome.

Ambulance calls and prehospital transportation time of emergency patients with cardiovascular events in Osaka City

This study investigated the association between the number of phone calls made to hospitals from ambulances requesting if they can accept prehospital emergency patients with cardiovascular events, and the prehospital transportation time.