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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.

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., Competing Interests: Osaka Metropolitan University and Dokkyo Medical University are attempting to file a patent application in Japan on the current findings. Tetsuro Nishimura from Osaka Metropolitan University and Toshihiro Hatakeyama from Dokkyo Medical University will be listed as inventors on the patent application related to this study. Toshihiro Hatakeyama also received an overseas scholarship from Dokkyo Medical University. Yohei Okada received a research grant from the ZOLL Foundation, an overseas scholarship from the FUKUDA Foundation for medical technology and a research grant from the International Medical Research Foundation. These organizations have no role in conducting this research. The other authors have no financial and personal relationships to declare., (© 2024 The Author(s).)

Objective: The purpose of this study was to clarify changes over time in suicidal tendencies among crisis hotline service users in Japan before and during the COVID-19 pandemic., Method: We analyzed telephone consultation data from January 2017 to June 2021 held by Inochi No Denwa, a leading organization providing a telephone crisis hotline in Japan. The number of monthly consultations by gender and the monthly counts of consultations identified by counselors as suicidal were collected, and we calculated trends over time in the proportion of suicidal calls by month using Joinpoint regression analysis., Results: The results indicated that the use of telephone crisis hotlines by suicidal callers increased significantly in Japan during the second wave of the pandemic in June to October 2020. These trends were also observed for both male and female users, although the increase began 1 month earlier for females than for males., Conclusion: Previous studies reported that mental health deteriorated and suicide risk increased significantly during the second wave of COVID-19 in Japan. These trends are consistent with the present findings, suggesting increased use of the crisis hotline by individuals at high suicide risk.

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., (© 2023. The Author(s).)

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.

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., Competing Interests: Declaration of competing interest All the authors declare that they have no potential conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Conflicts of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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)., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2023, corrected publication 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The rph gene cluster for prodigiosin biosynthesis has been identified in Streptomyces griseoviridis 2464-S5, which produces cyclic prodigiosin derivatives including roseophilin (2), prodigiosin R1 (3) and prodigiosin R2 (4). A new cyclic prodigiosin, prodigiosin R3 (1), was produced by the redG redP double disruptant of Streptomyces coelicolor M511 expressing four cyclization gene candidates (rphG, rphG2, rphG3 and rphG4) in the rph cluster. The same compound was isolated from Streptomyces griseoviridis 2464-S5. The molecular formula of 1 was established as C 27 H 33 N 3 O by ESI and FAB mass spectrometry. The structure was determined to be a multicyclic prodigiosin with three alkyl linkages by NMR spectroscopic analysis. Prodigiosin R3 (1) showed cytotoxicity against HeLa human cervical carcinoma cells and HT1080 human fibrosarcoma cells with IC 50 s of 2.1 µM and 3.2 µM, respectively., (© 2022. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

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., (Copyright © 2022. Published by Elsevier B.V.)

Genome-editing using the CRISPR-Cas9 system has the potential to substantially accelerate crop breeding. Since off-target editing is one of problems, a reliable method for comprehensively detecting off-target sites is needed. A number of in silico methods based on homology to on-target sequence have been developed, however the prediction without false negative is still under discussion. In this study, we performed a SITE-Seq analysis to predict potential off-target sites. SITE-Seq analysis is a comprehensive method that can detect double-strand breaks in vitro. Furthermore, we developed a systematic method using SITE-Seq in combination with web-based Galaxy system (Galaxy for Cut Site Detection), which can perform reproducible analyses without command line operations. We conducted a SITE-Seq analysis of a rice genome targeted by OsFH15 gRNA-Cas9 as a model, and found 41 candidate off-target sites in the annotated regions. Detailed amplicon-sequencing revealed mutations at one off-target site in actual genome-edited rice. Since this off-target site has an uncommon protospacer adjacent motif, it is difficult to predict using in silico methods alone. Therefore, we propose a novel off-target assessment scheme for genome-edited crops that combines the prediction of off-target candidates by SITE-Seq and in silico programs and the validation of off-target sites by amplicon-sequencing., (© 2022 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (© 2022. Springer Japan KK, part of Springer Nature.)

Aim: We aimed to identify subphenotypes among patients with out-of-hospital cardiac arrest (OHCA) with initial non-shockable rhythm by applying machine learning latent class analysis and examining the associations between subphenotypes and neurological outcomes., Methods: This study was a retrospective analysis within a multi-institutional prospective observational cohort study of OHCA patients in Osaka, Japan (the CRITICAL study). The data of adult OHCA patients with medical causes and initial non-shockable rhythm presenting with OHCA between 2012 and 2016 were included in machine learning latent class analysis models, which identified subphenotypes, and patients who presented in 2017 were included in a dataset validating the subphenotypes. We investigated associations between subphenotypes and 30-day neurological outcomes., Results: Among the 12,594 patients in the CRITICAL study database, 4,849 were included in the dataset used to classify subphenotypes (median age: 75 years, 60.2% male), and 1,465 were included in the validation dataset (median age: 76 years, 59.0% male). Latent class analysis identified four subphenotypes. Odds ratios and 95% confidence intervals for a favorable 30-day neurological outcome among patients with these subphenotypes, using group 4 for comparison, were as follows; group 1, 0.01 (0.001-0.046); group 2, 0.097 (0.051-0.171); and group 3, 0.175 (0.073-0.358). Associations between subphenotypes and 30-day neurological outcomes were validated using the validation dataset., Conclusion: We identified four subphenotypes of OHCA patients with initial non-shockable rhythm. These patient subgroups presented with different characteristics associated with 30-day survival and neurological outcomes., (© 2022 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

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., (© 2022. The Author(s).)

Introduction: Network meta-analyses (NMAs) of respiratory management strategies for acute hypoxemic respiratory failure (AHRF) have been reported, but no previous study has compared noninvasive ventilation (NIV), high-flow nasal oxygen (HFNO), standard oxygenation therapy (SOT), and invasive mechanical ventilation (IMV) for de novo AHRF. Therefore, we conducted an NMA to assess the effectiveness of these four respiratory strategies in patients with de novo AHRF., Methods: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Ichushi databases were searched. Studies including adults aged ≥18 years with AHRF and RCTs that compared two different oxygenation techniques (SOT, NIV, HFNO, or IMV) were selected. A frequentist-based approach with multivariate random-effects meta-analysis was used. The outcomes were mortality and intubation rates., Results: Among the 14,263 records initially identified, 25 studies (3302 patients) were included. In the analysis of mortality, compared to SOT, NIV (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.61-0.95) reduced mortality; however, IMV (RR, 1.01; 95% CI, 0.57-1.78) and HFNO (RR, 0.89; 95% CI, 0.66-1.20) did not. For assessments of the intubation incidence, compared to SOT, NIV use (RR, 0.63; 95% CI, 0.51-0.79) was associated with a reduction in intubation, but HFNO (RR, 0.82; 95% CI, 0.61-1.11) was not significant., Conclusions: Our NMA demonstrated that only NIV showed clinical benefits compared with SOT as an initial respiratory strategy for de novo AHRF. Further investigation, especially comparison with HFNO, is warranted., Trial Registration: PROSPERO (registration number: CRD42020213948 , 11/11/2020)., (© 2022. The Author(s).)

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 O 2 (PO 2 ), partial pressure of CO 2 (PCO 2 ) 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.

A neuroprotective compound (2) was isolated from the culture broth of the dutomycin (1) producer Streptomyces sp. RAP78. The molecular formula of 2 was established as C 44 H 55 NO 16 by high-resolution FAB-MS. The structure was determined to be a new dutomycin derivative possessing an acetimidoyl group in place of an acetyl group by NMR spectroscopic analysis. 13-Deoxo-13-iminodutomycin (2) but not dutomycin (1) protected C6 rat glioma cells and N18-RE-105 rat primary retina-mouse neuroblastoma hybrid cells from glutamate-induced toxicity with EC 50 s of 0.12 µM and 0.72 µM, respectively., (© 2021. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Background: Although non-invasive respiratory management strategies have been implemented to avoid intubation, patients with de novo acute hypoxaemic respiratory failure (AHRF) are high risk of treatment failure. In the previous meta-analyses, the effect of non-invasive ventilation was not evaluated according to ventilation modes in those patients. Furthermore, no meta-analyses comparing non-invasive respiratory management strategies with invasive mechanical ventilation (IMV) have been reported. We performed a network meta-analysis to compare the efficacy of non-invasive ventilation according to ventilation modes with high-flow nasal oxygen (HFNO), standard oxygen therapy (SOT), and IMV in adult patients with AHRF., Methods: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Ichushi databases were searched. Studies including adults with AHRF and randomized controlled trials (RCTs) comparing two different respiratory management strategies (continuous positive airway pressure (CPAP), pressure support ventilation (PSV), HFNO, SOT, or IMV) were reviewed., Results: We included 25 RCTs (3,302 participants: 27 comparisons). Using SOT as the reference, CPAP (risk ratio [RR] 0.55; 95% confidence interval [CI] 0.31-0.95; very low certainty) was associated significantly with a lower risk of mortality. Compared with SOT, PSV (RR 0.81; 95% CI 0.62-1.06; low certainty) and HFNO (RR 0.90; 95% CI 0.65-1.25; very low certainty) were not associated with a significantly lower risk of mortality. Compared with IMV, no non-invasive respiratory management was associated with a significantly lower risk of mortality, although all certainties of evidence were very low. The probability of being best in reducing short-term mortality among all possible interventions was higher for CPAP, followed by PSV and HFNO; IMV and SOT were tied for the worst (surface under the cumulative ranking curve value: 93.2, 65.0, 44.1, 23.9, and 23.9, respectively)., Conclusions: When performing non-invasive ventilation among patients with de novo AHRF, it is important to avoid excessive tidal volume and lung injury. Although pressure support is needed for some of these patients, it should be applied with caution because this may lead to excessive tidal volume and lung injury. Trial registration protocols.io (Protocol integer ID 49375, April 23, 2021). https://doi.org/10.17504/protocols.io.buf7ntrn ., (© 2021. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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 <0.001). However, the proportion of adult OHCA patients with favorable neurological outcome did not change during the study period (from 5.7% in 2013 to 4.4% in 2017, adjusted odds ratio (OR) for 1-year increment: 0.98 (95% confidence interval: 0.94-1.23))., Conclusions: In this target population, in-hospital management such as ECPR increased slightly between 2013 and 2017, but 1-month survival with favorable neurological outcome after adult OHCA did not improve significantly.

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.

A new member of the dunaimycin family, dunaimycin C3 (2), was isolated from a fermented broth of Streptomyces sp. RAN389. The molecular formula of 2 was established as C 42 H 70 O 10 by high-resolution FAB-MS, and the structure was elucidated by NMR spectroscopic analyses. Dunaimycin C3 inhibited the expression of the molecular chaperone GRP78 in HT1080 G-L cells in the presence of 10 mM of 2-deoxyglucose with an IC 50 of 8.4 nM.

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 (<65 years), time from call to hospital arrival (≤25 minutes), initial cardiac rhythm on hospital arrival (shockable), and initial pH value (≥7.0)., Main Outcomes and Measures: The primary outcome was 1-month survival with favorable neurological outcome, defined by Cerebral Performance Category 1 or 2. In the development cohort, a simple scoring system was developed to predict this outcome using a logistic regression model. The diagnostic ability and calibration of the scoring system were assessed in the validation cohort., Results: A total of 916 patients were included, 458 in the development cohort (median [interquartile range {IQR}] age, 61 [47-69] years, 377 [82.3%] men) and 458 in the validation cohort (median [IQR] age, 60 [49-68] years; 393 [85.8%] men). The cohorts had the same proportion of favorable neurological outcome (57 patients [12.4%]). The prediction scoring system was developed, attributing a score of 1 for each clinical predictor. Patients were divided into 4 groups, corresponding to their scores on the prediction model, as follows: very low probability (score 0), low probability (score 1), middle probability (score 2), and high probability (score 3-4) of good neurological outcome. The mean predicted probabilities in the groups stratified by score were as follows: very low, 1.6% (95% CI, 1.6%-1.6%); low, 4.4% (95% CI, 4.2%-4.6%); middle, 12.5% (95% CI, 12.1%-12.8%); and high, 30.8% (95% CI, 29.1%-32.5%). In the validation cohort, the C statistic of the scoring system was 0.724 (95% CI, 0.652-0.786). The predicted probability was evaluated as well calibrated to the observed favorable outcome in both cohorts by visual assessment of the calibration plot., Conclusions and Relevance: In this study, the scoring system had good discrimination and calibration performance to predict favorable neurological outcomes of patients with out-of-hospital cardiac arrest and shockable rhythm who were treated with ECPR.

A new curromycin-related compound, neocurromycin A (2), was isolated from the fermented broth of Streptomyces sp. RAI364. The molecular formula of 2 was established as C 35 H 44 N 4 O 7 by ESI-MS and the structure was elucidated by NMR spectroscopic analyses. Neocurromycin A showed selective cytotoxicity against MKN45 human gastric cancer cells in a nutrient-deprived medium with an IC 50 of 380 nM and inhibited the expression of the molecular chaperone GRP78 in HT1080 G-L cells in the presence of 10 mM of 2-deoxyglucose with an IC 50 of 1.7 µM.

Background: Oxidative stress is now recognized to be an important therapeutic target in kidney diseases. However, there are currently no biomarkers that can be used clinically to diagnose renal oxidative stress., Methods: A rapid assay system for urinary thioredoxin 1, an oxidative stress-dependent biomarker of acute kidney injury (AKI), was developed as a chemiluminescence enzyme immunoassay and validated analytically and clinically., Results: Analytic evaluation revealed that hemolytic hemoglobin caused measurements to be abnormally high, above the detectable range. However, urine sediment containing red blood cells did not affect the measurements. Assays using our proposed chemiluminescence enzyme immunoassay were completed within as little as 6 min, whereas a conventional ELISA > 4 h. Aciduria

Rapid DNA template preparation directly from a single rice ( Oryza sativa ) grain or rice flour of its equivalent weight was developed for loop-mediated isothermal amplification (LAMP). LAMP efficiency using DNA extract obtained from consecutive addition of alkaline lysis reagent (25 mM NaOH, 0.2 mM EDTA) and neutralizing reagent (40 mM Tris-HCl [pH 5]) was comparable to that using an equivalent amount of purified DNA as template. The stability of the prepared DNA extract was confirmed for up to six-day storage at room temperature. Without using any special laboratory devices, the developed method enabled a rapid, simple, and low-cost DNA template preparation method for reliable LAMP testing to detect rice genes.

Reinforcement of the hydroperoxide-eliminating activity in the small and large intestines should prevent associated diseases. We previously isolated a lactic acid bacterium, Pediococcus pentosaceus Be1 that facilitates a 2-electron reduction of hydrogen peroxide to water. In this study, we successfully isolated an alternative lactic acid bacterium, Lactobacillus plantarum P1-2, that can efficiently reduce environmental alkyl hydroperoxides and fatty acid hydroperoxides to their corresponding hydroxyl derivatives through a 2-electron reduction. Each strain exhibited a wide concentration range with regard to the environmental reducing activity for each hydroperoxide. Given this, the two lactic acid bacteria were orally administered to an oxygen-sensitive short-lived nematode mutant, and this resulted in a significant expansion of its lifespan. This observation suggests that P. pentosaceus Be1 and L. plantarum P1-2 inhibit internal oxidative stress. To determine the specific organs involved in this response, we performed a similar experiment in rats, involving induced lipid peroxidation by iron-overloading. We observed that only L. plantarum P1-2 inhibited colonic mucosa lipid peroxidation in rats with induced oxidative stress., Competing Interests: The authors have declared that no competing interests exist.

Genetically modified (GM) Atlantic salmon, AquAdvantage (AquAd), was the first GM animal approved officially for human consumption. Many countries monitor the use of this product under their GM regulations, but a pragmatic system for AquAd-specific detection is needed. Here, we developed a real-time polymerase chain reaction method with high sensitivity for detection of AquAd in foods. This method showed high specificity for the AquAd transgene and the detection limit was 12.5-25 targeted DNA copies per test reaction. An inter-laboratory study using the method developed demonstrated reproducibility at >0.1% (w/w) AquAd content., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ferredoxin NADP + oxidoreductase (Fpr) and oxygen-insensitive NAD(P)H nitroreductase (NfnB) are purified from Escherichia coli JM109 (E. coli JM109) as a predominant free flavin-independent ferric reductase. In the present study, we prepared natural iron storage proteins, E. coli ferritin A (FtnA) and bacterioferritin (Bfr), to show the effective ferrous iron release from these proteins by Fpr and NfnB in the presence of free flavins. Fpr and NfnB showed flavin reductase activity for flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and riboflavin, and their ferrous iron release activities were positively associated with the catalytic efficiencies (k cat /K m ) for individual flavins. The ferrous iron release activity of E. coli cell-free extracts was affected by flavin reductase activity of the extracts. The Butyl TOYOPEARL column chromatography of the extracts, on the basis of NAD(P)H-dependent flavin reductase activity, resulted in the separation of six active fractions containing Fpr, NfnB, NAD(P)H-quinone oxidoreductase (QOR), flavin reductase (Fre) or alkyl hydroperoxide reductase subunit F (AhpF) as major components. Like Fpr and NfnB, recombinant QOR, Fre, and AhpF showed flavin reductase activity and ferrous iron release activity in the presence of free flavins, indicating an association of flavin reductase activity with ferrous iron releasing activity. Taken together, both free flavin-dependent and free flavin-independent ferric reductases in E. coli require free flavins to mediate an electron transfer from NAD(P)H to ferric iron in the iron storage proteins for the effective ferrous iron release.