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BACKGROUND: The hypothesis of this study is that latent class analysis could identify the subphenotypes of out-of-hospital cardiac arrest (OHCA) patients associated with the outcomes and allow us to explore heterogeneity in the effects of extracorporeal cardiopulmonary resuscitation (ECPR).Methods and Results:This study was a retrospective analysis of a multicenter prospective observational study (CRITICAL study) of OHCA patients. It included adult OHCA patients with initial shockable rhythm. Patients from 2012 to 2016 (development dataset) were included in the latent class analysis, and those from 2017 (validation dataset) were included for evaluation. The association between subphenotypes and outcomes was investigated. Further, the heterogeneity of the association between ECPR implementation and outcomes was explored. In the study results, a total of 920 patients were included for latent class analysis. Three subphenotypes (Groups 1, 2, and 3) were identified, mainly characterized by the distribution of partial pressure of O2(PO2), partial pressure of CO2(PCO2) value of blood gas assessment, cardiac rhythm on hospital arrival, and estimated glomerular filtration rate. The 30-day survival outcomes were varied across the groups: 15.7% in Group 1; 30.7% in Group 2; and 85.9% in Group 3. Further, the association between ECPR and 30-day survival outcomes by subphenotype groups in the development dataset was as varied. These results were validated using the validation dataset. CONCLUSIONS: The latent class analysis identified 3 subphenotypes with different survival outcomes and potential heterogeneity in the effects of ECPR.

BACKGROUND: The aim of our study was to investigate in detail the temporal trends in in-hospital characteristics, actual management, and survival, including neurological status, among adult out-of-hospital cardiac arrest (OHCA) patients in recent years.Methods and Results:From the prospective database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan, we enrolled all OHCA patients aged ≥18 years for whom resuscitation was attempted, and who were transported to participating hospitals between the years 2013 and 2017. The primary outcome measure was 1-month survival with favorable neurological outcome after OHCA. Temporal trends in in-hospital management and favorable neurological outcome among adult OHCA patients were assessed. Of the 11, 924 patients in the database, we included a total of 10, 228 adult patients from 16 hospitals. As for in-hospital advanced treatments, extracorporeal cardiopulmonary resuscitation (ECPR) use increased from 2.4% in 2013 to 4.3% in 2017 (P for trend

We aimed to investigate the association between blood urea nitrogen to creatinine ratio (BCR) and survival with favourable neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA).This prospective, multicentre, observational study conducted in Osaka, Japan enrolled consecutive OHCA patients transported to 16 participating institutions from 2012 through 2019. We included adult patients with non-traumatic OHCA who achieved a return of spontaneous circulation and whose blood urea nitrogen and creatinine levels on hospital arrival were available. Based on BCR values, they were divided into: 'low BCR' (BCR10), 'normal BCR' (10 ≤ BCR 20), 'high BCR' (20 ≤ BCR 30), and 'very high BCR' (BCR ≥ 30). We evaluated the association between BCR values and neurologically favourable outcomes, defined as cerebral performance category score of 1 or 2 at one month after OHCA.Among 4415 eligible patients, the 'normal BCR' group had the highest favourable neurological outcome [19.4 % (461/2372)], followed by 'high BCR' [12.5 % (141/1127)], 'low BCR' [11.2 % (50/445)], and 'very high BCR' groups [6.6 % (31/471)]. In the multivariable analysis, adjusted odds ratios for 'low BCR', 'high BCR', and 'very high BCR' compared with 'normal BCR' for favourable neurological outcomes were 0.58 [95 % confidence interval (CI 0.37-0.91)], 0.70 (95 % CI 0.49-0.99), and 0.40 (95 % CI 0.21-0.76), respectively. Cubic spline analysis indicated that the association between BCR and favourable neurological outcomes was non-linear (p for non-linearity = 0.003). In subgroup analysis, there was an interaction between the aetiology of arrest and BCR in neurological outcome (p for interaction0.001); favourable neurological outcome of cardiogenic OHCA patients was lower when the BCR was higher or lower, but not in non-cardiogenic OHCA patients.Both higher and lower BCR were associated with poor neurological outcomes compared to normal BCR, especially in cardiogenic OHCA patients.

The effect of post-cardiac arrest care in children with out-of-hospital cardiac arrest (OHCA) has not been adequately established, and the long-term outcome after pediatric OHCA has not been sufficiently investigated. We describe here detailed in-hospital characteristics, actual management, and survival, including neurological status, 90 days after OHCA occurrence in children with OHCA transported to critical care medical centers (CCMCs). We analyzed the database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITI-CAL) study, which is a multicenter, prospective observational data registry designed to accumulate both pre-and in-hospital data on OHCA treatments. We enrolled all consecutive pediatric patients aged

Background Bioactive lipid mediators play a crucial role during infection. Previously, we showed the expression level of FAAH mRNA in septic patients was lower than in healthy controls. Case Presentation Four patients with a Sequential Organ Failure Assessment (SOFA) score of

Background: Serum lactate reflects hypoxic insult in many conditions, but its role as prognostic markers after cardiac arrest is still controversial. This study aimed to investigate the association between serum lactate levels during cardiopulmonary resuscitation (CPR) and survival in patients with out-of-hospital cardiac arrest (OHCA).Methods:We analyzed the data of the Osaka Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study, a prospective multicenter observational study of 14 participating institutions in Osaka Prefecture, Japan that enrolled consecutive OHCA patients. We included adult nontraumatic OHCA patients transported to the hospital with ongoing CPR from 2013 to 2017. Based on the serum lactate levels during CPR, the patients were divided into four quartiles: Q1 (lactate ≤ 10.6 mEq/L), Q2 (10.6 < lactate ≤ 14.1 mEq/L), Q3 (14.1 < lactate ≤ 18.0 mEq/L), and Q4 (lactate > 18.0 mEq/L). The primary outcome of this study was 1-month survival. Results:A total of 11,960 patients were registered and 4,978 of them were eligible for our analyses. The Q1 group had the highest 1-month survival (4.3% [53/1,245]), followed by Q2 (2.5% [31/1,245]), Q3 (1.1% [14/1,328]), and Q4 (0.5% [6/1,160]) groups. In the multivariable logistic regression analysis, the proportion of 1-month survival in the Q4 group was significantly lower than that in the Q1 group (adjusted odds ratio 0.21; 95% confidence interval 0.086 to 0.50). One-month survival decreased in a stepwise manner as the quartiles increased (p for trend CONCLUSION:High serum lactate level during CPR was associated with poor 1-month survival in OHCA patients. Serum lactate may be one of the effective prognostic indications for OHCA during CPR, especially in patients with non-shockable rhythm.

The effect of post-cardiac arrest care in children with out-of-hospital cardiac arrest (OHCA) has not been adequately established, and the long-term outcome after pediatric OHCA has not been sufficiently investigated. We describe here detailed in-hospital characteristics, actual management, and survival, including neurological status, 90 days after OHCA occurrence in children with OHCA transported to critical care medical centers (CCMCs).We analyzed the database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study, which is a multicenter, prospective observational data registry designed to accumulate both pre- and in-hospital data on OHCA treatments. We enrolled all consecutive pediatric patients aged18 years who had an OHCA and for whom resuscitation was attempted and who were transported to CCMCs between 2012 and 2016.A total of 263 pediatric patients with OHCA were enrolled. The average age of the patients was 6.3 years, 38.0% were aged1 year, and 60.8% were male. After hospital arrival, 4.9% of these pediatric patients received defibrillation; 1.9%, extracorporeal life support; 6.5%, target temperature management; and 88.2% adrenaline administration. The proportions of patients with 90-day survival and a pediatric cerebral performance category (PCPC) score of 1 or 2 were 6.1% and 1.9%, respectively. The proportion of patients with a PCPC score of 1 or 2 at 90 days after OHCA occurrence did not significantly improve during the study period.The proportion of pediatric patients with a 90-day PCPC score of 1 or 2 transported to CCMCs was extremely low, and no significant improvements were observed during the study period.

Background We aimed to identify the association of pH value in blood gas assessment with neurological outcome among out-of-hospital cardiac arrest (OHCA) patients treated by extracorporeal cardiopulmonary resuscitation (ECPR). Methods We retrospectively analysed the database of a multicentre prospective observational study to collect pre-hospital and in-hospital data among OHCA patients in Osaka prefecture, Japan (CRITICAL study), from 1 July 2012 to 31 December 2016. We included the adult OHCA patients treated by ECPR with blood gas assessment before starting ECPR. Patients with OHCA of external causes, such as trauma, were excluded. The patients were divided into three approximately equal groups based on the pH values. We conducted logistic regression analysis to identify the odds ratio (OR) and 95% confidence interval (CI) of the groups for the 1-month neurological favourable outcome adjusted by the potential confounders of sex, age, witnessed by bystander, CPR by bystander, pre-hospital initial cardiac rhythm, and cardiac rhythm on hospital arrival. Results Among the 9,822 patients in the database, 260 patients were finally included in the analysis. The three groups were Tertile 1: pH ≥7.030, Tertile 2: pH 6.875-7.029, and Tertile 3: pH

Key Points Question Can the neurological outcome of patients with out-of-hospital cardiac arrest and shockable rhythm who are treated with extracorporeal cardiopulmonary resuscitation (ECPR) be predicted using accessible information? Findings In this prognostic study of 916 patients, a model using time to hospital arrival, pH in initial blood gas assessment, shockable rhythm on hospital arrival, and being younger than 65 years was developed to predict survival with good neurological outcome. The model had good performance and was well calibrated. Meaning These findings suggest that this model may be useful for predicting the neurological outcomes of patients with out-of-hospital cardiac arrest and shockable rhythm treated with ECPR., This prognostic study develops and validates a prediction model for neurological outcomes of patients with out-of-hospital cardiac arrest with shockable rhythm treated with extracorporeal cardiopulmonary resuscitation., Importance Extracorporeal cardiopulmonary resuscitation (ECPR) is expected to improve the neurological outcomes of patients with refractory cardiac arrest; however, it is invasive, expensive, and requires substantial human resources. The ability to predict neurological outcomes would assist in patient selection for ECPR. Objective To develop and validate a prediction model for neurological outcomes of patients with out-of-hospital cardiac arrest with shockable rhythm treated with ECPR. Design, Setting, and Participants This prognostic study analyzed data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a multi-institutional nationwide cohort study that included 87 emergency departments in Japan. All adult patients with out-of-hospital cardiac arrest and shockable rhythm who were treated with ECPR between June 2014 and December 2017 were included. Patients were randomly assigned to the development and validation cohorts based on the institutions. The analysis was conducted between November 2019 and August 2020. Exposures Age (

Acetaminophen (APAP) induced increases in intrahepatic expression of interleukin (IL)-1 alpha, IL-1 beta, and IL-1 receptor antagonist (IL-1ra), when administered intraperitoneally. These observations prompted us to define the pathophysiological roles of IL-1ra in APAP-induced liver injury. Compared with wild-type (WT) mouse-derived hepatocytes, IL-1ra-deficient (IL-1ra KO)-derived hepatocytes exhibited more resistance against APAP but not APAP-derived major toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Moreover, the amounts of a major APAP adduct (selenium-binding protein), an indicator of NAPQI generation from APAP, was significantly lower in IL-1ra KO mice than WT mice with depressed intrahepatic expression of CYP1A2, CYP2E1, and CYP3A11, the enzymes crucially involved in NAPQI generation from APAP. These observations would indicate that IL-1ra deficiency impaired APAP metabolism. IL-1 alpha and IL-1 beta were expressed to similar extents in livers of untreated IL-1ra KO and WT mice. By contrast, the intranuclear amount of p65 of NF-kappaB, which can suppress the gene expression of CYP1A2, CYP2E1, and CYP3A11, was higher in untreated IL-1ra KO than WT mice. Moreover, when mice were intraperitoneally administered APAP (200 mg/kg), IL-1ra KO mice exhibited attenuated APAP-induced liver injury as evidenced by reductions in serum alanine transferase levels and histopathological changes such as centrilobular necrosis, hemorrhages, and leukocyte infiltration. Finally, when given 12 h before APAP challenge, IL-1 alpha repressed the intrahepatic expression of CYP1A2, CYP2E1, and CYP3A11, eventually reducing APAP-induced liver injury, along with reduction in APAP adducts. Collectively, NF-kappaB was activated without any stimuli by the genetic disruption of IL-1ra, and suppressed cytochrome P450 enzyme expression, thereby reducing APAP-induced liver injury.