Search

Excitatory synapses are formed and matured by the cooperative actions of synaptic organizers, such as neurexins (Nrxns), neuroligins (Nlgns), LRRTMs, and Cbln1. Recent super-resolution nanoscopy developments have revealed that many synaptic organizers, as well as glutamate receptors and glutamate release machinery, exist as nanoclusters within synapses. However, it is unclear how such nanodomains interact with each other to organize excitatory synapses in vivo. By applying X10 expansion microscopy to epitope tag knockin mice, we found that Cbln1, Nlgn1, and LRRTM1, which share Nrxn as a common presynaptic receptor, form overlapping or separate nanodomains depending on Nrxn with or without a sequence encoded by splice site 4. The size and position of glutamate receptor nanodomains of GluD1, NMDA, and AMPA receptors were regulated by Cbln1, Nlgn1, and LRRTM1 nanodomains, respectively. These findings indicate that Nrxns anterogradely regulate the postsynaptic nanoscopic architecture of glutamate receptors through competition and coordination of Nrxn ligands. [Display omitted] • Expansion microscopy revealed the nanoscopic architecture of excitatory synapses • Nlgn1, LRRTM1, and Cbln1 formed nanoclusters independently of PSD-95 • The presynaptic Nrxn isoforms regulate Nlgn1, LRRTM1, and Cbln1 nanoclusters • Nlgn1, LRRTM1, and Cbln1 nanoclusters are linked to glutamate receptor subtypes Synaptic organizers, such as neuroligin1, LRRTM1, and Cbln1, commonly target neurexin. Using X10 expansion microscopy, Nozawa et al. revealed that presynaptic neurexin isoforms regulated nanoclusters of postsynaptic neurexin ligands and glutamate receptor subtypes. Their findings provide models of how neurexin ligands coordinate or compete to organize excitatory synapses in vivo. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Extracorporeal cardiopulmonary resuscitation (ECPR) is performed in refractory out-of-hospital cardiac arrest (OHCA) patients, and the eligibility has been conventionally determined based on three criteria (initial cardiac rhythm, time to hospital arrival within 45 minutes, and age <75 years) in Japan. Owing to limited information, this study descriptively determined neurological outcomes after applying the three criteria among OHCA patients who underwent ECPR.Methods: This study conducted a post-hoc analysis of data from the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study. This was a multi-institutional prospective observational study of OHCA patients in Osaka Prefecture, Japan. All adult (aged ≥18 years) OHCA patients with internal medical causes treated with ECPR between 1 July 2012 and 31 December 2019 were evaluated. We described one-month neurological favourable outcomes based on the three criteria (initial shockable, time to hospital arrival within 45 minutes, and age <75 years), and we compared them using the chi-square test.Results: Among 18,379 patients screened from the CRITICAL study database, we included 517 OHCA patients treated by ECPR; 311 (60.2%) patients met all three criteria. Favourable neurological outcomes were as follows: patients meeting no or one criterion: 2.3% (1/43), those meeting two criteria: 8% (13/163), and those meeting all criteria: 16.1% (50/311) (P-value = 0.004).Conclusions: In this study, approximately 60% of patients treated by ECPR met the three criteria (initial shockable, time to hospital arrival within 45 minutes, and age <75 years), and the greater the number of criteria met, the better were the neurological outcomes achieved. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To develop and validate a model for the early prediction of long-term neurological outcome in patients with non-traumatic out-of-hospital cardiac arrest (OHCA).Methods: We analysed multicentre OHCA registry data of adult patients with non-traumatic OHCA who experienced return of spontaneous circulation (ROSC) and had been admitted to the intensive care unit between 2013 and 2017. We allocated 1329 (2013-2015) and 1025 patients (2016-2017) to the derivation and validation sets, respectively. The primary outcome was the dichotomized cerebral performance category (CPC) at 90 days, defined as good (CPC 1-2) or poor (CPC 3-5). We developed 2 models: model 1 included variables without laboratory data, and model 2 included variables with laboratory data available immediately after ROSC. Logistic regression with least absolute shrinkage and selection operator regularization was employed for model development. Measures of discrimination, accuracy, and calibration (C-statistics, Brier score, calibration plot, and net benefit) were assessed in the validation set.Results: The C-statistic (95% confidence intervals) of models 1 and 2 in the validation set was 0.947 (0.930-0.964) and 0.950 (0.934-0.966), respectively. The Brier score of models 1 and 2 in the validation set was 0.0622 and 0.0606, respectively. The calibration plot showed that both models were well-calibrated to the observed outcome. Decision curve analysis indicated that model 2 was similar to model 1.Conclusion: The prediction tool containing detailed in-hospital information showed good performance for predicting neurological outcome at 90 days immediately after ROSC in patients with OHCA. [ABSTRACT FROM AUTHOR]

We aimed to investigate the association between serum lactate levels during cardiopulmonary resuscitation (CPR) and survival in patients with out-of-hospital cardiac arrest (OHCA). From the database of a multicenter registry on OHCA patients, we included adult nontraumatic OHCA patients transported to the hospital with ongoing CPR. Based on the serum lactate levels during CPR, the patients were divided into four quartiles: Q1 (≤ 10.6 mEq/L), Q2 (10.6–14.1 mEq/L), Q3 (14.1–18.0 mEq/L), and Q4 (> 18.0 mEq/L). The primary outcome was 1-month survival. Among 5226 eligible patients, the Q1 group had the highest 1-month survival (5.6% [74/1311]), followed by Q2 (3.6% [47/1316]), Q3 (1.7% [22/1292]), and Q4 (1.0% [13/1307]) groups. In the multivariable logistic regression analysis, the adjusted odds ratio of Q4 compared with Q1 for 1-month survival was 0.24 (95% CI 0.13–0.46). 1-month survival decreased in a stepwise manner as the quartiles increased (p for trend < 0.001). In subgroup analysis, there was an interaction between initial rhythm and survival (p for interaction < 0.001); 1-month survival of patients with a non-shockable rhythm decreased when the lactate levels increased (p for trend < 0.001), but not in patients with a shockable rhythm (p for trend = 0.72). In conclusion, high serum lactate level during CPR was associated with poor 1-month survival in OHCA patients, especially in patients with non-shockable rhythm. [ABSTRACT FROM AUTHOR]

Background: Sudden cardiac arrest is a serious complication of acute myocardial infarction (MI). Although in-hospital mortality from MI has decreased, the mortality of MI patients complicated with out-of-hospital cardiac arrest (OHCA) remains high. However, the features of acute MI patients with OHCA have not been well known.Objectives: We sought to characterize the clinical and angiographic features of acute MI patients with OHCA comparing with those without OHCA.Methods: We retrospectively analyzed 480 consecutive patients with acute MI undergoing percutaneous coronary intervention. Patients complicated with OHCA were compared with patients without OHCA.Results: Of the patients, 141 (29%) were complicated with OHCA. Multivariate analysis revealed that age (odds ratio [OR]: 0.8; 95% confidence interval [CI]: 0.7 to 0.9 per 5 years; p < 0.001), estimated glomerular filtration rate (OR: 0.8; 95% CI: 0.7 to 0.8 per 10 ml/min/1.73 m2; p < 0.001), peak creatine kinase-myocardial band (OR: 1.3; 95% CI: 1.2 to 1.4 per 102 U/l; p < 0.001), calcium-channel antagonists use (OR: 0.4; 95% CI: 0.2 to 0.7; p = 0.002), the culprit lesion at the left main coronary artery (OR: 5.3; 95% CI: 1.9 to 15.1; p = 0.002), and the presence of chronic total occlusion (OR: 2.9; 95% CI: 1.5 to 5.7; p = 0.001) were significantly associated with OHCA.Conclusions: Younger age, no use of calcium-channel antagonists, worse renal function, larger infarct size, culprit lesion in the left main coronary artery, and having chronic total occlusion were associated with OHCA. [ABSTRACT FROM AUTHOR]

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 analyzed the database of a multicenter prospective observational study on OHCA patients in Osaka prefecture, Japan (CRITICAL study), from July 1, 2012 to December 31, 2016. We included adult OHCA patients treated by ECPR. Patients with OHCA from external causes such as trauma were excluded. We conducted logistic regression analysis to identify the odds ratio (OR) and 95% confidence interval (CI) of the pH value for 1 month favorable neurological outcome adjusted for potential confounders including sex, age, witnessed by bystander, CPR by bystander, pre-hospital initial cardiac rhythm, and cardiac rhythm on hospital arrival. Results: Among the 9822 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 < 6.875. The adjusted OR of Tertiles 2 and 3 compared with Tertile 1 for 1 month favorable neurological outcome were 0.26 (95% CI 0.10–0.63) and 0.24 (95% CI 0.09–0.61), respectively. Conclusions: This multi-institutional observational study showed that low pH value (< 7.03) before the implementation of ECPR was associated with 1 month unfavorable neurological outcome among OHCA patients treated with ECPR. It may be helpful to consider the candidate for ECPR. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to evaluate the out‐of‐hospital cardiac arrest (OHCA) characteristics of patients stratified by age who had resuscitation attempted and were transported to tertiary emergency medical institutions in Osaka Prefecture, Japan; especially those of advanced age. Methods: A prospective, population‐based, observational review was carried out of consecutive OHCA patients with emergency responder resuscitation attempts from July 2012 to December 2016 in Osaka, Japan. Patients were classified into four groups: (i) 18–64 years; (ii) 65–74 years; (iii) 75–84 years; and (iv) ≥85 years. Patient, event and treatment characteristics were examined for patients with presumed cardiac etiology of OHCA. The primary outcome was the 1‐month survival with a neurologically favorable outcome. Results: A total of 4636 patients with OHCA of presumed cardiac origin were transported to tertiary emergency medical institutions. The number of patients in the four groups was as follows: (i) 1290 (27.8%); (ii) 1102 (23.8%); (iii) 1420 (30.6%); and (iv) 824 (17.8%). The 1‐month survival with a neurologically favorable outcome was: (i) 207 (16.0%); (ii) 96 (8.7%); (iii) 60 (4.2%); and (iv) seven (0.85%). In a multivariate analysis for 1‐month survival with a neurologically favorable outcome, increased age was a significant prognostic factor (≥85 years; adjusted odds ratio 0.08, 95% confidence interval 0.03–0.23) for poor outcomes. Conclusions: In this population, advanced age (≥85 years) was strongly associated with poor outcomes. Further discussion of policies directed at resuscitation of very elderly OHCA patients is required, considering limited medical resources and the rapidly aging population in Japan. Geriatr Gerontol Int 2019; 19: 1088–1095. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate whether intra-aortic balloon pump (IABP) use in nontraumatic out-of-hospital cardiac arrest (OHCA) patients who achieved return of spontaneous circulation (ROSC) is associated with favorable neurological outcome after OHCA.Background: The association between the IABP use in OHCA patients and favorable neurological outcome has not been extensively evaluated.Methods: The Comprehensive Registry of Intensive Cares for OHCA Survival (CRITICAL) study, a multicenter, prospective observational registry in Osaka, Japan, included consecutive nontraumatic OHCA patients aged ≥18 years who achieved ROSC from July 2012 to December 2016. The primary outcome was 1-month survival with favorable neurological outcome. Logistic regression analysis was used to evaluate the association between the IABP use or non-IABP use and favorable neurological outcome using one-to-one propensity score (PS) matching analysis.Results: Among the 2894 eligible patients, 10.4% used IABP, and 89.6% did not use IABP. In all patients, the proportion of 1-month survival with favorable neurological outcome was higher in the IABP use group than in the non-IABP use group (30.7% [92/300] vs. 13.2% [342/2594]). However, in PS-matched patients, the proportions of 1-month survival with favorable neurological outcome were almost consistent, and there were no significant differences between the IABP use group and the non-IABP use group (37.3% [59/158] vs. 41.1% [65/158]; adjusted odds ratio, 0.97; 95% confidence interval, 0.48-1.96).Conclusions: In this population, the current PS matching analysis did not reveal any association between the IABP use and 1-month survival with favorable neurological outcome among adult patients with ROSC after OHCA. [ABSTRACT FROM AUTHOR]

Background: It has been insufficiently investigated whether neurological function after out-of-hospital cardiac arrest (OHCA) would differ by 1 °C change in ordered target temperature of 33-36 °C among patients undergoing targeted temperature management (TTM) in the real-world setting.Methods: This nationwide hospital-based observational study (The Japanese Association for Acute Medicine-OHCA Registry) conducted between June 2014 and December 2015 in Japan included OHCA patients aged ≥18 years who were treated with TTM. The primary outcome was one-month survival with neurologically favorable outcomes defined by cerebral performance category 1 or 2. To investigate the effect of TTM by 1 °C change in ordered target temperature of 33-36 °C on each outcome, random effects logistic regression analyses were performed.Results: The final analysis included 738 patients. The proportion of patients with neurologically favorable outcome was 30.4% (7/23), 31.7% (175/552), 28.9% (11/38), and 30.4% (38/125) in the 33 °C, 34 °C, 35 °C, and 36 °C groups, respectively. In the multivariable logistic regression analysis, no group had a higher proportion of neurologically favorable outcome compared with the 34 °C group (vs. 33 °C group, adjusted odds ratio [AOR] 0.90; 95% confidence interval [CI] 0.25-3.12, vs. 35 °C group, AOR 1.17; 95% CI 0.44-3.13, vs. 36 °C group, AOR 1.26; 95% CI 0.78-2.02).Conclusions: In this population, we evaluated the difference in outcomes after adult OHCA patients received TTM by 1 °C change in ordered target temperature of 33-36 °C and demonstrated that there was no statistically significant difference in neurologically favorable outcomes after OHCA irrespective of target temperature. [ABSTRACT FROM AUTHOR]

Keywords: cardiopulmonary resuscitation; heart arrest EN cardiopulmonary resuscitation heart arrest 1031 1033 3 04/20/20 20200324 NES 200324 Extracorporeal cardiopulmonary resuscitation (ECPR) is expected to benefit the rescue of selected patients, particularly those who are refractory to conventional cardiopulmonary resuscitation (CPR).[1] Considering its invasive procedure and considerable resources, establishing a helpful criterion for initiating ECPR remains crucial. Low-flow duration (LFD) is one of the most common criteria to identify candidates for ECPR.[1] However, the association between LFD and favorable neurological outcome has not been sufficiently investigated in out-of-hospital cardiac arrests (OHCAs). LFD was defined as the time interval from initiation of any CPR (bystander CPR or CPR by emergency medical services personnel) to the initiation of ECPR. [Extracted from the article]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Key Clinical Message Bacterial meningitis can be difficult to recognize: the meningeal triad symptoms are not always present and the alteration in mental status can mimic heatstroke. Escherichia coli meningitis is a serious disease whose early diagnosis, appropriate antibiotic treatment, and hemodynamic management are essential. [ABSTRACT FROM AUTHOR]

The patient in this case report was an 88-year-old male. Acute upper airway obstruction by food led to transient cardiac arrest, and negative pressure pulmonary hemorrhage (NPPH) occurred 1 hour after the foreign body obstruction. Using venovenous extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome resulting from NPPH, his respiratory state was recovered and hemoptysis stopped. NPPH is a life-threatening disease, the rapid recognition of which is required to initiate appropriate therapy. Although active hemorrhage might be a contraindication for ECMO, our experience showed this to be an effective treatment option. Moreover, our experience suggests that the application of ECMO to elderly patients should be considered on a case-by-case basis. [ABSTRACT FROM AUTHOR]