Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis.

BACKGROUND: Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC syndrome have previously been examined, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review on the combined administration of AT and rTM for the treatment of septic DIC to investigate the superiority of the combination therapy over either AT or rTM monotherapy using a random-effects analysis model. METHOD: We searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was occurrence of serious bleeding complications compared to monotherapy. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study. RESULTS: We analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy (HR 0.67 [0.43-1.05], OR 0.73 [0.45-1.18]). The I2 values were 60% and 72%, respectively, suggesting high heterogeneity. As a secondary outcome, bleeding complications were similar between the two groups (pooled OR 1.11 [0.55-2.23], I2 value 55%). CONCLUSIONS: Although the findings in this analysis could not confirm a statistically significant effect of AT and rTM combination therapy for septic DIC, it showed a promising effect in terms of improving mortality. The incidence of bleeding was low and clinically feasible. Further research is warranted to draw more conclusive results. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: 000049820).

In-hospital extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: an analysis by time-dependent propensity score matching using a nationwide database in Japan.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score. METHODS: This was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model. RESULTS: Of 57,754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR, n = 913 and control, n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR, n = 370 and control, n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38-2.25] for shockable rhythm and 5.37 [95%CI 2.53-11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82-1.49] for shockable rhythm and 4.25 [95%CI 1.43-12.63] for non-shockable rhythm, compared to controls. CONCLUSION: ECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR.

Severity of SARS-CoV-2 infection in pregnant women and their neonates during the Omicron period compared to the pre-Omicron period: A retrospective cohort study.

AIM: To compare the clinical outcomes among women diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy, and their neonates, during the period when the Omicron variant predominated in Japan with those of the pre-Omicron variant period. METHODS: We conducted a retrospective single-center cohort study between August 1, 2020, and June 30, 2022. The cohort was divided into pre-Omicron group (August 1, 2020 to November 30, 2021) and Omicron group (December 1, 2021 to June 30, 2022). The primary outcome was maternal intensive care unit (ICU) admission during the perinatal period. The secondary outcomes were maternal oxygen administration before and after delivery, preterm birth (PTB), and low birth weight (LBW). RESULTS: During the study period, 81 pregnant women were admitted to the hospital with SARS-CoV-2 infection (pre-Omicron period, n = 28; Omicron period, n = 53). SARS-CoV-2 infection during the Omicron period was associated with lower risk of maternal ICU admission (adjusted-odds ratio [aOR]: 0.10, 95% confidence interval [CI]: 0.01-1.23, p = 0.072), oxygen administration via a nasal cannula or mask (aOR: 0.18, 95% CI: 0.03-0.96, p = 0.045), PTB (aOR: 0.15, 95% CI: 0.04-0.51, p = 0.002), and LBW (aOR: 0.13, 95% CI: 0.03-0.55, p = 0.005). CONCLUSION: Among pregnant women, SARS-CoV-2 infection during the Omicron period was associated with reduced risk of maternal ICU admission, requiring supplemental oxygen, PTB, and LBW. This can be attributable to lower virulence of the Omicron variant and higher vaccination coverage during the Omicron period.

Steric Interaction of Polyglycerol-Functionalized Detonation Nanodiamonds.

Detonation nanodiamonds have found numerous potential applications in a diverse array of fields such as biomedical imaging and drug delivery. Here, we systematically characterized non-functionalized and polyglycerol-functionalized detonation nanodiamond particles (DNPs) dispersed in aqueous suspensions at different ionic strengths (∼1.0 × 10-7 to 1.0 × 10-2 M) via dynamic light scattering and cryogenic transmission electron microscopy. For these colloidal suspensions, the total potential energies of interactions between a pair of DNPs were theoretically calculated using the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory plus the fitting of the Boltzmann distribution to the interparticle spacing distribution of the colloidal DNPs. These investigations revealed that the non-functionalized DNPs are dispersed in aqueous media through the long-range (>10 nm) and weak (<7 kBT) electrical double-layer repulsive interaction, while the driving force on dispersion of polyglycerol-functionalized DNPs is mostly derived from the short-range (<2 nm) and strong (∼55 kBT) steric repulsive potential barrier generated by the polyglycerol. Moreover, our results show that the truly monodispersed and individually dispersed DNP colloids, forming no aggregates in aqueous suspensions, are available by both functionalizing DNPs by polyglycerol and increasing ionic strength of suspending media to ≳1.0 × 10-2 M.

Search for the Decomposition Process of 2,4,6-Trinitrotoluene by an Evolutionary Algorithm.

In this paper, we explored stable states in the system of 2,4,6-trinitrotoluene (TNT) crystal with a few additional hydrogen radicals (Hadd's) using a structure-search scheme based on first-principles calculations and an evolutionary algorithm (EA) to get insights into the decomposition process of TNT. We introduced three evolutionary operators acting on Hadd's and transforming only local structures of TNT molecules: "displacement", "permutation", and "mating". We searched for stable structures by increasing the number of Hadd's (n) from 1 to 2, 3, 4, 6, and 8 and constructed a convex-hull diagram for the formation energy from solid TNT and solid hydrogen. We showed that the system of n = 6 had the largest energy reduction, in which five of the eight TNT molecules in the calculation cell were transformed into NO, H2O, C2H3N, C2NO3H3, C8N2O4H7, C9N2O8H5, and C14N7O12H11. Analysis of the structural transformations observed during the EA search indicates that (1) the Hadd's approaching the TNT molecules react with C, forming a six-membered ring, and with N and O in nitro groups, leaving the TNT molecules as NO, H2O, C2H3N, and C2NO3H3, and (2) the partially decomposed TNT molecules are bonded to one another via C, N, and O.

Early prognostic impact of serum sodium level among out-of-hospital cardiac arrest patients: a nationwide multicentre observational study in Japan (the JAAM-OHCA registry).

Dysnatremia is an electrolytic disorder commonly associated with mortality in various diseases. However, little is known about dysnatremia in out-of-hospital cardiac arrest (OHCA) cases. Here, we investigated the association between serum sodium level on hospital arrival and neurological outcomes after OHCA. This nationwide hospital-based observational study (The Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry) enrolled patients with OHCA between 2014 and 2017. We included adult patients aged ≥ 18 years with non-traumatic OHCA who achieved return of spontaneous circulation (ROSC) and whose serum sodium level on hospital arrival was available. Based on the serum sodium level, patients were divided into three levels: hyponatremia (Na < 135 mEq/L), normal sodium level (Na ≥ 135 or ≤ 145 mEq/L), and hypernatremia (Na > 145 mEq/L). The primary outcome was 1-month survival with favourable neurological outcomes. Altogether, 34 754 patients with OHCA were documented, and 5160 patients with non-traumatic OHCA and who achieved ROSC were eligible for our analyses. The proportion of favourable neurological outcomes was highest in patients with normal sodium levels at 17.6% (677/3854), followed by patients with hyponatremia at 8.2% (57/696) and patients with hypernatremia at 5.7% (35/610). Moreover, hyponatremia and hypernatremia were associated with a decreased probability of favourable neurological outcomes compared with normal sodium level (vs. hyponatremia, adjusted odds ratio [AOR] 0.97, 95% confidence interval [CI] 0.95-0.99; vs. hypernatremia, AOR 0.96, 95% CI 0.94-0.98). Hypo- and hypernatremia on hospital arrival were associated with a decreased probability of favourable neurological outcomes in patients with non-traumatic OHCA who achieved ROSC.

Predictive accuracy of the shock index for severe postpartum hemorrhage in high-income countries: A systematic review and meta-analysis.

AIM: The shock index has been suggested as a screening tool for predicting postpartum hemorrhage (PPH); however, there is little comprehensive evidence regarding its predictive accuracy. This systematic review and meta-analysis aim to investigate the predictive accuracy of the shock index for severe PPH in high-income countries. METHODS: A comprehensive search was conducted on MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science (from inception to June 2021). Studies assessing the predictive performance of the shock index for PPH in high-income countries were included. Two or more reviewers independently extracted the data and assessed the risk of bias and applicability concerns using the modified Quality Assessment of Diagnostic Accuracy Studies 2 tool. PPH requiring higher-level care, such as blood transfusions, were considered as primary analyses. We described the hierarchical summary receiver-operating characteristic curve for data synthesis. RESULTS: Nine studies were included after the eligibility assessment. All studies were considered to either have a high risk of bias or high applicability concerns. The sensitivity of the four studies that defined severe PPH as PPH requiring blood transfusion ranged from 0.51 to 0.80, whereas their specificity ranged from 0.33 to 0.92. CONCLUSIONS: This review shows that the predictive performance of the shock index for severe PPH is inconsistent. Therefore, the evidence for using the shock index alone as a screening tool for PPH in high-income countries is insufficient. STUDY REGISTRATION: This review was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000044230).

Association between initial body temperature on hospital arrival and neurological outcome among patients with out-of-hospital cardiac arrest: a multicenter cohort study (the CRITICAL study in Osaka, Japan).

BACKGROUND: The association between spontaneous initial body temperature on hospital arrival and neurological outcomes has not been sufficiently studied in patients after out-of-hospital cardiac arrest (OHCA). METHODS: From the prospective database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan, we enrolled all patients with OHCA of medical origin aged > 18 years for whom resuscitation was attempted and who were transported to participating hospitals between 2012 and 2019. We excluded patients who were not witnessed by bystanders and treated by a doctor car or helicopter, which is a car/helicopter with a physician. The patients were categorized into three groups according to their temperature on hospital arrival: ≤35.9 °C, 36.0-36.9 °C (normothermia), and ≥ 37.0 °C. The primary outcome was 1-month survival, with a cerebral performance category of 1 or 2. Multivariable logistic regression analyses were performed to evaluate the association between temperature and outcomes (normothermia was used as the reference). We also assessed this association using cubic spline regression analysis. RESULTS: Of the 18,379 patients in our database, 5014 witnessed adult OHCA patients of medical origin from 16 hospitals were included. When analyzing 3318 patients, OHCA patients with an initial body temperature of ≥37.0 °C upon hospital arrival were associated with decreased favorable neurological outcomes (6.6% [19/286] odds ratio, 0.51; 95% confidence interval, 0.27-0.95) compared to patients with normothermia (16.4% [180/1100]), whereas those with an initial body temperature of ≤35.9 °C were not associated with decreased favorable neurological outcomes (11.1% [214/1932]; odds ratio, 0.78; 95% confidence interval, 0.56-1.07). The cubic regression splines demonstrated that a higher body temperature on arrival was associated with decreased favorable neurological outcomes, and a lower body temperature was not associated with decreased favorable neurological outcomes. CONCLUSIONS: In adult patients with OHCA of medical origin, a higher body temperature on arrival was associated with decreased favorable neurologic outcomes.

Association between pregnant women fasting duration and neonatal hypoglycemia: A prospective cohort study.

OBJECTIVE: To evaluate the association between maternal fasting time before delivery and the occurrence of hypoglycemia in neonates immediately after birth. METHODS: This prospective single-center cohort study included pregnant women who delivered at the study institution between October 2021 and January 2023 and their neonates. The primary outcome was the incidence of neonatal hypoglycemia after birth, defined as a blood glucose level less than 47 mg/dL. Fasting time was categorized into quartiles, and the association between maternal fasting time and neonatal hypoglycemia was investigated. The crude or adjusted odds ratios of maternal fasting time for neonatal hypoglycemia were calculated using logistic regression analysis. RESULTS: The study included 663 pregnant women and 696 neonates. Compared with the reference group with a short fasting time of 4.3 h or less, the adjusted odds ratios for neonatal hypoglycemia were 1.47 (95% confidence interval [CI] 0.70-3.20) for middle fasting time (4.3-9.8 h), 4.05 (95% CI 2.02-8.56) for long fasting time (9.8-14.6 h), and 4.99 (95% CI 2.59-10.25) for very long fasting time (>14.6 h). In the subgroup analysis, the association between maternal fasting time and neonatal hypoglycemia showed different trends according to the mode of delivery. CONCLUSION: Maternal fasting time over 9-10 h before delivery was associated with the occurrence of neonatal hypoglycemia. Obstetrical management, considering not only maternal safety but also neonatal hypoglycemia prevention, is required.

Efficacy of antithrombin administration for patients with sepsis: A systematic review, meta-analysis, and meta-regression.

Aims: There have been inconsistent reports regarding the effect of antithrombin on sepsis; furthermore, there are limited reports on how dosage affects therapeutic efficacy. Thus, we aimed to perform a systematic review and meta-analysis of the use of antithrombin for sepsis and a meta-regression analysis of antithrombin dosage. Methods: We included randomized controlled trials (RCTs) and observational studies of adult patients with sepsis who received antithrombin. Outcomes included all-cause mortality and serious bleeding complications. Statistical analyses and data synthesis were performed using a random-effects model; further, meta-regression and funnel plots were used to explore heterogeneity and biases. Results: Seven RCTs and six observational studies were included. Most patients in the RCTs and observational studies had severe sepsis and septic-disseminated intravascular coagulation (DIC), respectively. A meta-analysis using RCTs showed no significant differences in mortality between the antithrombin and control groups. However, the meta-analysis of observational studies indicated a trend of decreasing mortality rates with antithrombin administration (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.68-0.92; p = 0.002). Bleeding complications were significantly higher in the antithrombin group than in the control group in both study types (OR, 1.90; 95% CI, 1.52-2.37; p < 0.01). The meta-regression analysis showed no correlation between antithrombin dosage and mortality. Conclusion: A meta-analysis of RCTs confirmed no survival benefit of antithrombin, whereas that of observational studies, which mostly focused on septic DIC, showed a significant beneficial effect on improving outcomes. Indications of antithrombin should be considered based on its beneficial and harmful effects.

Non-linear association between the time required to reaching temperature targets and the neurological outcome in patients undergoing targeted temperature management after out-of-hospital cardiac arrest: Observational multicentre cohort study.

Purpose: We evaluated associations between outcomes and time to achieving temperature targets during targeted temperature management of out-of-hospital cardiac arrest. Methods: Using Comprehensive Registry of Intensive Care for out-of-hospital cardiac arrest Survival (CRITICAL) study, we enrolled all patients transported to participating hospitals from 1 July 2012 through 31 December 2017 aged ≥ 18 years with out-of-hospital cardiac arrest of cardiac aetiology and who received targeted temperature management in Osaka, Japan. Primary outcome was Cerebral Performance Category scale of 1 or 2 one month after cardiac arrest, designated as "one-month favourable neurological outcome". Non-linear multivariable logistic regression analyses assessed the primary outcome based on time to reaching temperature targets. In patients subdivided into quintiles based on time to achieving temperature targets, multivariable logistic regression calculated adjusted odds ratios and 95% confidence intervals. Results: We analysed 473 patients. In non-linear multivariable logistic regression analysis, p value for non-linearity was < 0.01. In the first quintile (< 26.7 minutes), second quintile (26.8-89.9 minutes), third quintile (90.0-175.1 minutes), fourth quintile (175.2-352.1 minutes), and fifth quintile (≥ 352.2 minutes), one-month favourable neurological outcome was 32.6% (31/95), 40.0% (36/90), 53.5% (53/99), 57.4% (54/94), and 37.9% (36/95), respectively. Adjusted odds ratios with 95% confidence intervals for one-month favourable neurological outcome in the first, second, third, and fifth quintiles compared with the fourth quintile were 0.38 (0.20 to 0.72), 0.43 (0.23 to 0.81), 0.77 (0.41 to 1.44), and 0.46 (0.25 to 0.87), respectively. Conclusion: Non-linear multivariable logistic regression analysis could clearly describe the association between neurological outcome in patients with out-of-hospital cardiac arrest and the time from the introduction of targeted temperature management to reaching the temperature targets.

External Validation of Updated Prediction Models for Neurological Outcomes at 90 Days in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset. METHODS AND RESULTS: We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d_lasso/). CONCLUSIONS: The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

Divisively normalized neuronal processing of uncertain visual feedback for visuomotor learning.

When encountering a visual error during a reaching movement, the motor system improves the motor command for the subsequent trial. This improvement is impaired by visual error uncertainty, which is considered evidence that the motor system optimally estimates the error. However, how such statistical computation is accomplished remains unclear. Here, we propose an alternative scheme implemented with a divisive normalization (DN): the responses of neuronal elements are normalized by the summed activity of the population. This scheme assumes that when an uncertain visual error is provided by multiple cursors, the motor system processes the error conveyed by each cursor and integrates the information using DN. The DN model reproduced the patterns of learning response to 1-3 cursor errors and the impairment of learning response with visual error uncertainty. This study provides a new perspective on how the motor system updates motor commands according to uncertain visual error information.

Epidemiology and outcomes of pregnant trauma patients in Japan: a nationwide descriptive study.

PURPOSE: Trauma during pregnancy is the leading indirect obstetric cause of death, and its management is challenging owing to its characteristics. We aimed to describe the epidemiology of pregnant trauma patients and explore their characteristics by comparing them with those of non-pregnant patients. METHODS: Using the Japan Trauma Data Bank data collected between January 2004 and May 2019, we identified pregnant and non-pregnant female trauma patients between the ages of 15-45 years. We described patient characteristics, prehospital information, in-hospital management, and clinical outcomes. We also investigated the differences in the information between pregnant and non-pregnant patients. RESULTS: In total, 165 pregnant trauma patients were identified (0.7%). Motor vehicle collisions were the most frequent mechanism of injury (64.6%) in pregnant patients. The time from call to the arrival of emergency medical services at the hospital was similar for both pregnant and non-pregnant patients. The use of abdominal computed tomography (CT) scans was lower and injury to the abdomen was more frequent in pregnant than non-pregnant patients. In-hospital mortality was 7.2% in pregnant patients and 10.9% in non-pregnant patients. No significant differences in mortality after adjustment for confounding factors were found (adjusted odds ratio: 0.78, 95% confidential interval: 0.35-1.75, p = 0.548). CONCLUSION: Transport time and mortality were similar between pregnant and non-pregnant trauma patients. Abdominal trauma and surgery were more common in pregnant relative to non-pregnant patients, while the number of CT scans was less. Further research is required to investigate the effects of trauma on the course of pregnancy and the fetus.

Efficacy of sleep extension therapy using a remote support system in university students with increased social jetlag: a parallel, single-blind, randomized controlled trial.

Purpose: The efficacy of sleep extension therapy using a remote support system (SET-R) was investigated in university students with increased social jetlag (SJL). Methods: For this two-arm parallel randomized controlled trial, we recruited Japanese university students with SJL ≥ 60 min. The SET-R provided an individualized sleep schedule for gradual sleep extension using email and sleep hygiene education, stimulus control therapy, and progressive muscle relaxation as web content. The control group was sent an email that encouraged them to record their sleep. The duration of the intervention program was two weeks. The primary outcome was the mean change in SJL two weeks later, assessed using the Munich ChronoType Questionnaire (MCTQ). The other outcomes included Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale (ESS), Insomnia Severity Index, Patient Health Questionnaire-9 (PHQ-9), and sleep quiz. A follow-up survey was conducted 6 months after the intervention. Results: Of 54 students, 26 were assigned to an intervention group and 28 to a control group. The difference in the mean change in SJL between the two groups (n = 26, n = 27) at two weeks was statistically significant (27.7 min, P = 0.048). The scores for the ESS, PHQ-9, and sleep quiz were improved in the intervention group relative to the control group. At the 6-month follow-up point, the difference in the mean change in SJL between the two groups (n = 22, n = 27) was not statistically significant, but scores for the PHQ-9, and sleep quiz remained significant. Conclusions: This study demonstrated the efficacy of the SET-R among university students with increased SJL. Trial Registration: The study was registered with the UMIN Clinical Trials Registry (UMIN000042634, 2021/02/01).

Correction: Efficacy of sleep extension therapy using a remote support system in university students with increased social jetlag: a parallel, single-blind, randomized controlled trial.

[This corrects the article DOI: 10.1007/s41105-023-00453-5.].

External validation of the TiPS65 score for predicting good neurological outcomes in patients with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation.

AIM: Estimating prognosis of patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) is essential for selecting candidates. The TiPS65 score can predict neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) treated with ECPR. We aimed to perform an external validation of this score. METHODS: Data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a multicentred, nationwide, prospectively registered database, were analysed. All adult patients with OHCA and shockable rhythm and treated with ECPR between January 2018 to December 2019 were included. In the TiPS65 score, age, call-to-hospital arrival time, initial cardiac rhythm at hospital arrival, and initial pH value were used as predictors. The primary outcome was 30-day survival with favourable neurological outcomes (Cerebral Performance Category 1 or 2). Discrimination, using the C-statistic, and predictive performances of each score, such as sensitivity and specificity, were investigated. RESULTS: Of 590 included patients (517 [81.6%] men; median [interquartile range] age, 60 [50-69] years), 64 (10.8%) reported favourable neurological outcomes. The C-statistic of the TiPS65 score was 0.729 (95% confidence interval (CI): 0.672-0.786). When the cut-off of TiPS65 score was set to >1, the sensitivity and specificity were 0.906 (95%CI: 0.807-0.965) and 0.430 (95%CI: 0.387-0.473), respectively; conversely, when the cut-off was set to >3, they were 0.172 (95%CI: 0.089-0.287) and 0.971 (95%CI: 0.953-0.984), respectively. CONCLUSIONS: The TiPS65 score shows reasonable discrimination and predictive performances. This score can be supportive in the decision-making process for the selection of eligible patients for ECPR in clinical settings.

Association between blood urea nitrogen to creatinine ratio and neurologically favourable outcomes in out-of-hospital cardiac arrest in adults: A multicentre cohort study.

BACKGROUND: 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). METHODS: 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' (BCR <10), '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. RESULTS: 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 interaction <0.001); favourable neurological outcome of cardiogenic OHCA patients was lower when the BCR was higher or lower, but not in non-cardiogenic OHCA patients. CONCLUSIONS: Both higher and lower BCR were associated with poor neurological outcomes compared to normal BCR, especially in cardiogenic OHCA patients.

Diagnostic test accuracy of life-threatening electrocardiographic findings (ST-elevation myocardial infarction equivalents) for acute coronary syndrome after out-of-hospital cardiac arrest without ST-segment elevation.

AIM: Life-threatening electrocardiographic (ECG) findings aid in the diagnosis of acute coronary syndrome (ACS), which has not been well-evaluated in patients with out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate the diagnostic test accuracy (DTA) of ST-elevation myocardial infarction (STEMI) equivalents following the return of spontaneous circulation (ROSC) in patients with OHCA to identify patients with ACS. METHODS: Using the database of the Comprehensive Registry of In-Hospital Intensive Care for OHCA Survival study from 2012 to 2017, patients aged ≥18 years with non-traumatic OHCA and ventricular fibrillation or pulseless ventricular tachycardia on the arrival of emergency medical service personnel or arrival at the emergency department, who achieved ROSC, were included. Patients without ST-segment elevation or complete left bundle branch block on ECG and those who did not undergo ECG or coronary angiography, were excluded from the study. We evaluated the DTA of STEMI equivalents for the diagnosis of ACS: isolated T-wave inversion, ST-segment depression, Wellens' signs, and ST-segment elevation in lead aVR. RESULTS: Isolated T-wave inversion and Wellens' signs had high specificity for ACS with 0.95 (95% confidence interval [CI], 0.87-0.99) and 0.92 (95% CI, 0.82-0.97), respectively, but their positive likelihood ratios were low, with a wide range of 95% CI: 1.89 (95% CI, 0.51-7.02) and 0.81 (95% CI, 0.25-2.68), respectively. CONCLUSION: The DTA of STEMI equivalents for the diagnosis of ACS was low among patients with OHCA. Further investigation considering the measurement timing of the ECG after ROSC is required.

Intra-Aortic Balloon Pump among Shockable Out-of-Hospital Cardiac Arrest Patients: A Propensity-Weighted Analysis in a Multicenter, Nationwide Observational Study in Japan (The JAAM-OHCA Registry).

BACKGROUND: The effectiveness of IABP for shockable out-of-hospital cardiac arrest (OHCA) has not been extensively investigated. This study aimed to investigate whether the use of an intra-aortic balloon pump (IABP) for non-traumatic shockable OHCA patients was associated with favorable neurological outcomes. METHODS: From the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a nationwide multicenter prospective registry, we enrolled adult patients with non-traumatic and shockable OHCA for whom resuscitation was attempted, and who were transported to participating hospitals between 2014 and 2019. The primary outcome was 1-month survival with favorable neurological outcomes after OHCA. After adopting the propensity score (PS) inverse probability of weighting (IPW), we evaluated the association between IABP and favorable neurological outcomes. RESULTS: Of 57,754 patients in the database, we included a total of 2738 adult non-traumatic shockable patients. In the original cohort, the primary outcome was lower in the IABP group (OR with 95% confidence intervals (CIs)), 0.57 (0.48-0.68), whereas, in the IPW cohort, it was not different between patients with and without IABP (OR, 1.18; 95% CI, 0.91-1.53). CONCLUSION: In adult patients with non-traumatic shockable OHCA, IABP use was not associated with 1-month survival with favorable neurological outcomes.