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Purpose: Long non-coding RNAs (lncRNAs) constitute a group of non-coding RNAs longer than 200 nucleotides. LncRNAs are able to regulate almost every stage of gene expression, from epigenetic modification to post-transcriptional regulation. Recent landmark studies revealed that lncRNAs are involved in cardiac development. However, the role of lncRNAs in cardiac diseases is unknown. Here, we investigated the regulation of lncRNAs in the hypertrophied heart.Methods: Wild-type and adenosine A2a receptor overexpressing mice (A2a-Tg) were subjected to transverse aortic constriction (TAC) as a model of cardiac hypertrophy or doxorubicin treatment as a model of cardiotoxicity. Hearts were harvested and expression of lncRNAs was investigated using Affymetrix Mouse Gene 1.0 ST microarrays. A specific analytical pipeline was developed to extract from these microarrays the data related to lncRNAs.Results: Analysis of microarray data identified 2 lncRNAs up-regulated and 3 down-regulated in the hearts of A2a-Tg mice subjected to TAC. Quantitative PCR showed that expression of the lncRNA 2900055J20Rik was highly down-regulated in A2a-Tg mice compared to wild-type littermates (-3.5-fold, P<0.001). To confirm the association between 2900055J20Rik and cardiac hypertrophy, we used a public microarray dataset from mice subjected to TAC. In this public dataset, expression of 2900055J20Rik was found to be up-regulated in TAC mice compared to sham-operated animals (6-fold after 28 days, P<0.01). Interestingly, administration of the BET bromodomain inhibitor JQ1, a suppressor of cardiac hypertrophy, resulted in a decrease of 2900055J20Rik expression 3, 11 and 28 days after treatment onset (P<0.01). Finally, to investigate the effect of adenosine on the expression of 2900055J20Rik in another model of cardiac stress, wild-type and A2a-Tg mice were treated with doxorubicin. As it was observed in TAC mice, expression of 2900055J20Rik was down-regulated upon overexpression of the adenosine A2a receptor in doxorubicin-treated animals (2-fold, P=0.03).Conclusions: First, we have shown that data on lncRNAs can be obtained from traditional gene expression microarrays. Second, lncRNAs are regulated in the hypertrophied heart and can be modulated by cardioprotective molecules (adenosine and JQ1). Third, we have identified the lncRNA 2900055J20Rik which may be involved in regulation of cardiac hypertrophy. These observations motivate further investigation of the therapeutic value of lncRNAs in the diseased heart. [ABSTRACT FROM PUBLISHER]

Demyelination and axonal degeneration are fundamental pathological characteristics of multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS). Although the molecular mechanisms driving these processes are not fully understood, hepatocyte growth factor (HGF) has emerged as a potential regulator of neuroinflammation and tissue protection in MS. Elevated HGF levels have been reported in MS patients receiving immunomodulatory therapy, indicating its relevance in disease modulation. This study investigated HGF's neuroprotective effects using transgenic mice that overexpressed HGF. The experimental autoimmune encephalomyelitis (EAE) model, which mimics MS pathology, was employed to assess demyelination and axonal damage in the CNS. HGF transgenic mice showed delayed EAE progression, with reduced CNS inflammation, decreased demyelination, and limited axonal degeneration. Scanning electron microscopy confirmed the preservation of myelin and axonal integrity in these mice. In addition, we explored HGF's effects using a cuprizone-induced demyelination model, which operates independently of the immune system. HGF transgenic mice exhibited significant protection against demyelination in this model as well. We also investigated the expression of key HGF receptors, particularly c-Met and KAI-1. While c-Met, which is associated with increased inflammation, was upregulated in EAE, its expression was significantly reduced in HGF transgenic mice, correlating with decreased neuroinflammation. Conversely, KAI-1, which has been linked to axonal protection and stability, showed enhanced expression in HGF transgenic mice, suggesting a protective mechanism against axonal degeneration. These findings underscore HGF's potential in preserving CNS structure and function, suggesting it may be a promising therapeutic target for MS, offering new hope for mitigating disease progression and enhancing neuroprotection.

Aims: Guidelines recommend non-invasive positive pressure ventilation (NPPV) for patients with acute decompensated heart failure (ADHF) with an inadequate response to initial oxygen therapy. During Japan's coronavirus disease 2019 pandemic, NPPV use in emergency departments (EDs) was limited due to aerosol-spreading concerns. This study compared the respiratory management and clinical outcomes of patients with ADHF in EDs before and during the pandemic., Methods and Results: This retrospective cohort study was conducted at a single centre in Japan using hospital data from September to November 2019 (before the pandemic) and September to November 2020 (during the pandemic). Patients diagnosed with ADHF were included. Patients not responding to standard oxygen therapy were intubated or started on NPPV therapy. The primary outcome measure was discharge after death. The secondary outcomes were length of hospital stay and medical expenses. The study included 37 patients before the pandemic and 36 during the pandemic. No significant differences were found in vital signs or laboratory data between the groups. NPPV utilization decreased significantly from 26 (70.3%) to 7 (19.4%) (P < 0.01). Two patients required intubation during both periods, with no significant differences (P = 0.98). No significant intergroup disparities were observed in discharge after death (1/36 [2.7%] vs. 1/37 [2.7%]; P = 0.19), length of hospital stay (17.5 vs. 19.0 days; P = 0.65), and medical expenses (57 590 vs. 57 600 yen; P = 0.65)., Conclusions: Despite a large decrease in NPPV use before and during the pandemic, there were no significant differences in discharge after death, hospital stay, or medical expenses., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: With the advent of multiplex polymerase chain reaction (PCR) using samples from a positive blood culture, the time required to identify a pathogen has significantly shortened to a few hours. It can help us select appropriate antimicrobial agents more quickly. The present study aimed to assess the impact of using a multiplex PCR blood culture panel on the appropriate administration of antimicrobial agents., Methods: Patients aged <16 years with culture-confirmed bacteremia at Tokyo Metropolitan Children's Medical Center were enrolled. A pre-intervention period (period I: December 2016 to December 2018) and a post-intervention period with multiplex PCR use for the confirmation of positive blood cultures (period II: December 2019 to December 2021) were compared for their effect on the use of antimicrobial agents for gram-positive cocci (GPC) and gram-negative rod (GNR) bacteremia. Data on patient background, blood culture results, and antimicrobial use were retrospectively collected from electronic medical records., Results: Periods I and II had 174 and 154 patients, respectively. The median age at periods I and II was 14 (IQR 2-82) months and 12 (IQR 1-78) months, respectively. GPC bacteremia during periods I and II occurred in 140 and 115 patients, respectively. GNR during periods I and II occurred in 34 and 39 patients, respectively. Neither the vancomycin-resistance genes A/B nor the carbapenem-resistance gene were detected. The use of antimicrobial agents against anti-methicillin-resistant Staphylococcus aureus (MRSA) for GPC bacteremia decreased from 103/140 cases (73%) in period I to 56/115 cases (49%) in period II (p=0.047). The use of carbapenems for GNR bacteremia did not change significantly, at 23/34 (68%) in period I and 34/39 (87%) in period II (p=0.47)., Conclusion: Introducing multiplex PCR for pediatric bacteremia decreased the use of anti-MRSA antimicrobial agents but not of carbapenems., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Tokyo Metropolitan Children’s Medical Center issued approval 2022b-41. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kuruma et al.)

Owing to the miniaturization of diagnostic ultrasound scanners and their spread of their bedside use, ultrasonography has been actively utilized in emergency situations. Ultrasonography performed by medical personnel with focused approaches at the bedside for clinical decision-making and improving the quality of invasive procedures is now called point-of-care ultrasonography (POCUS). The concept of POCUS has spread worldwide; however, in Japan, formal clinical guidance concerning POCUS is lacking, except for the application of focused assessment with sonography for trauma (FAST) and ultrasound-guided central venous cannulation. The Committee for the Promotion of POCUS in the Japanese Association for Acute Medicine (JAAM) has often discussed improving the quality of acute care using POCUS, and the "Clinical Guidance for Emergency and Point-of-Care Ultrasonography" was finally established with the endorsement of JAAM. The background, targets for acute care physicians, rationale based on published articles, and integrated application were mentioned in this guidance. The core points include the fundamental principles of ultrasound, airway, chest, cardiac, abdominal, and deep venous ultrasound, ultrasound-guided procedures, and the usage of ultrasound based on symptoms. Additional points, which are currently being considered as potential core points in the future, have also been widely mentioned. This guidance describes the overview and future direction of ultrasonography for acute care physicians and can be utilized for emergency ultrasound education. We hope this guidance will contribute to the effective use of ultrasonography in acute care settings in Japan., Competing Interests: Dr. Akio Kimura is an Editorial Board member of AMS Journal and a co‐author of this article. To minimize bias, he was excluded from all editorial decision‐making related to the acceptance of this article for publication. The Japanese version of this paper was published in the July 2022 issue of the Journal of the Japanese Association for Acute Medicine (JJAAM). The authors have obtained permission for the secondary publication of the English version of the editors of the JJAAM., (© 2024 The Author(s). Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

The global prevalence of atrial fibrillation (AF) is rising, paralleling increased life expectancy. Early rhythm control benefits AF management. However, in low-risk, often asymptomatic, AF patients, anticoagulant monotherapy is the selected treatment, aligning with current guidelines. However, early AF progression in these low-risk individuals is not well-understood. Thus, this study aims to: 1) determine the proportion of low-risk AF patients who worsen within a year of initial AF diagnosis and 2) identify risk factors such treatment transitions. We analyzed data from 18623 AF patients, spanning January 2005 to June 2017. Low-risk patients were those on anticoagulant monotherapy ± rate control, following the JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias. We defined 2 patterns of treatment transition for 1) initiating ablation or antiarrhythmic drug therapy and 2) solely using antiarrhythmic drugs. This retrospective cohort study was employed a 12-month study, following a 6-month screening period. We included 1874 patients for all rhythm control (analysis 1) and 1503 for only medication-based control (analysis 2). The primary endpoint, treatment transition of AF under monotherapy, occurred in 28.4% of patients in analysis 1 and 10.8% in analysis 2. Risk factors common to both scenarios were male gender, baseline rate control drug use, and rivaroxaban selection, as identified by multiple logistic regression. These findings suggest a higher AF treatment transition trend in patients starting rivaroxaban, calling for further research. The study highlights the importance of informed early rhythm control initiation decisions in clinical settings.

Background: Door to balloon time is a crucial factor of mortality in patients with ST-segment elevation myocardial infarction. However, the factors that contribute to failure of achieving door to balloon time ≤ 90 min in an electrocardiogram triage system remain unknown., Methods: This single-center retrospective observational study collected data from consecutive patients with ST-segment elevation myocardial infarction from April 2016 to March 2021. The primary outcome was the failure to achieve door to balloon time ≤ 90 min. A multivariate logistic regression model was performed to predict factors associated with failure to achieve door to balloon time ≤ 90 min., Results: In total, 190 eligible patients were included. Of these, the 139 (73.2%) patients with door to balloon time ≤ 90 min were significantly younger compared to those with door to balloon time > 90 min (p = 0.02). However, there was no significant difference in sex and timing of hospital arrival between the door to balloon time ≤ 90 and > 90 min groups. Presence of chest pain and ambulance usage were significantly more frequent in patients with door to balloon time ≤ 90 min (p ≤ 0.01, p = 0.02, respectively). Multivariate analysis showed that absence of chest pain (adjusted odds ratio 4.76; 95% confidence interval, 2.04-11.1; p < 0.01) and non-ambulance usage (adjusted odds ratio 3.53; 95% confidence interval, 1.57-7.94; p < 0.01) are predictive factors of failure to achieve door to balloon time ≤ 90 min., Conclusion: Patients without chest pain as the chief complaint or non-ambulance usage were significantly associated with the failure to achieve door to balloon time ≤ 90 min., (© 2023. The Author(s).)

Aim: Capnography is recommended for use in procedural sedation and analgesia (PSA); however, limited studies assess its impact on recovery time. We investigated the association between capnography and the recovery time of PSA in the emergency department (ED)., Methods: This study was a secondary analysis of a multicenter PSA patient registry including eight hospitals in Japan. We included all patients who received PSA in the ED between May 2017 and May 2021 and divided the patients into capnography and no-capnography groups. The primary outcome was recovery time, defined as the time from the end of the procedure to the cessation of monitoring. The log-rank test and multivariable analysis using clustering for institutions were performed., Results: Of the 1265 screened patients, 943 patients who received PSA were enrolled and categorized into the capnography ( n  = 150, 16%) and no-capnography ( n  = 793, 84%) groups. The median recovery time was 40 (interquartile range [IQR]: 25-63) min in the capnography group and 30 (IQR: 14-55) min in the no-capnography group. In the log-rank test, the recovery time was significantly longer in the capnography group ( p  = 0.03) than in the no-capnography group. In the multivariable analysis, recovery time did not differ between the two groups (adjusted hazard ratio, 0.95; 95% confidence interval, 0.77-1.17; p  = 0.61)., Conclusion: In this secondary analysis of the multicenter registry of PSA in Japan, capnography use did not associate with shorter recovery time in the ED., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Objective: Burnout negatively affects the wellness and performance of emergency physicians (EPs). This study aimed to clarify the actual prevalence of burnout and its associated factors among Japanese EPs., Methods: We conducted a cross-sectional questionnaire study of selected 27 Japanese emergency departments (EDs). We examined the Maslach Burnout Inventory-Human Services Survey score and its associations with ED-level- and EP-level factors in a multivariable analysis., Results: A total of 267 EPs (81.9%) completed survey. Of these, 43 EPs (16.1%) scored severe emotional exhaustion (EE), 53 (19.8%) scored severe depersonalization (DP), and 179 (67.0%) scored severe personal accomplishment (PA), and 24 (8.9%) scored severely in all three domains. In our multivariable analysis, emergency medical service centers were associated with severe PA scores (odds ratio [OR], 10.56; 95% confidence interval [CI], 1.78-62.66; p  = 0.009). A 3 to 6 hour-sleep period was associated with severe EE scores (OR, 2.04; 95% CI, 1.04-3.98; p  = 0.036), and EPs in their 20s were associated with severe DP scores (OR, 7.37; 95% CI, 1.41-38.38; p  = 0.018)., Conclusion: Our results suggest that 8.9% of Japanese EPs are in higher degrees of burnout. In particular, Japanese EPs scored more severely on PA. To avoid burnout in Japanese EPs, it is important to improve the working environment by ensuring more than 6 h of sleep, providing more support for young EPs, and taking effective action to combat low EP self-esteem., Competing Interests: Authors declare no conflict of interest for this article., (© 2023 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background: Chemotherapy and chemoradiotherapy are common treatments for esophageal squamous cell carcinoma with distant metastasis; however, the prognosis remains poor, and complete remission is difficult to achieve. Here, we report a case of an older adult patient with esophageal squamous cell carcinoma who underwent surgery following combined treatment of immunotherapy and chemotherapy and achieved pathological complete response., Case Presentation: An 80-year-old woman presenting with difficulty swallowing was referred to our hospital. She was diagnosed with esophageal squamous cell carcinoma with distant metastasis of the lymph node at the dorsal side of the IVC and the left supraclavicular lymph node. She was treated with pembrolizumab, cisplatin, and 5-fluorouracil. After four pharmacotherapy courses, primary tumor and metastatic lymph node shrinkage was observed. The patient underwent thoracoscopic subtotal esophagectomy and regional lymph node dissection. The lymph node at the dorsal side of the IVC was not resected, and the left supraclavicular lymph node was removed. Histological examination revealed complete response with no residual tumor or lymph node metastasis. The patient had no recurrence 10 months postoperatively without adjuvant chemotherapy., Conclusions: Conversion surgery following preoperative therapy, including immunotherapy, may be an effective treatment strategy for improving survival in patients with esophageal squamous cell carcinoma even among older adult patients., (© 2023. The Author(s).)

The advancement in epigenetics research over the past several decades has led to the potential application of epigenome-editing technologies for the treatment of various diseases. In particular, epigenome editing is potentially useful in the treatment of genetic and other related diseases, including rare imprinted diseases, as it can regulate the expression of the epigenome of the target region, and thereby the causative gene, with minimal or no modification of the genomic DNA. Various efforts are underway to successfully apply epigenome editing in vivo, such as improving target specificity, enzymatic activity, and drug delivery for the development of reliable therapeutics. In this review, we introduce the latest findings, summarize the current limitations and future challenges in the practical application of epigenome editing for disease therapy, and introduce important factors to consider, such as chromatin plasticity, for a more effective epigenome editing-based therapy.

Background: In Japan, the nurse practitioner (NP) system has only been in place for a short time, and there is no ultrasound (US) simulation course for NPs. Therefore, NPs may have to attend US simulation courses for physicians. We evaluated whether US simulation course for physicians lead to improved image acquisition and interpretation amongst NPs and, if so, if these changes would be maintained over time., Methods: A 2-day point-of-care ultrasound (POCUS) course designed for physicians in cardiac US, lung US, lower extremity deep vein thrombosis (DVT) US, and abdominal US was held for Japanese nurse practitioners (JNP) and JNP trainees in 2018 and 2019. Participants kept a record of the number of US examinations they performed for 3 months before and 3 months after the course. The number of US exams performed was grouped into six categories. All participants underwent pre-course, immediate post-course, and 4-month post-course testing to assess image interpretation skills, image acquisition skills, and confidence., Results: Thirty-three participants from 21 facilities completed the program. Before and immediately after the course, test scores of the image interpretation test, image acquisition test, and confidence increased significantly (37.1, 72.6: P < 0.001), (13.7, 53.6: P < 0.001), and (15.8, 35.7: P < 0.001), respectively. Comparing the follow-up tests immediately after the course and 4 months later, there was no decrease in scores on the image interpretation test, the image acquisition test, or confidence (72.6, 71.8: P = 1.00) (53.6, 52.9: p = 1.00) (35.7, 33.0: P = 0.34). There was a statistically significant increase (P < 0.001) in both the total number of ultrasound examinations and in the number of ultrasound examinations by category (cardiac, lung, lower extremity DVT, and abdominal) in the 3 months before and 3 months after the course., Conclusions: The POCUS simulation course for physicians is useful for JNPs to acquire US examination skills even if it is not arranged for JNPs. Image interpretation skill, image acquisition skill, and confidence improved significantly and were maintained even after 4 months of the course. It leads to behavioral changes such as increasing the number of US examinations in daily practice after the course., (© 2023. The Author(s).)

Background: Blood culture is critical in treating infectious diseases. This leads to unnecessary intervention, inappropriate antibiotic use, and excess cost. Few studies have tackled patient factors that could possibly affect contamination rates. This study aimed to explore the association between patients' nursing care levels and blood culture contamination., Methods: This is a single-centered, retrospective, case-control study of adult patients whose blood culture specimens were taken in the emergency department between April 2018 and July 2019. The study was conducted in an acute care community hospital in Japan. The case group included patients with false-positive blood culture results with contamination; the control group included patients with true-positive or true-negative blood culture results without contamination. We randomly selected two control patients per case. Patients' age, gender, nursing care level, ambulance use, housing status, Glasgow Coma Scale, hospital arrival time, and puncture sites were obtained from the patients' medical charts., Results: Of the 5130 patients, 686 patients got positive blood culture results. Of the 686 patients, 35 patients were included in the case group, and 70 were randomly selected from the noncontaminated group and included in the control. In multivariate analysis, patients with contaminated blood cultures had a higher nursing care level (adjusted odds ratio: 8.50; 95% confidence interval: 1.65-43.7; p  = 0.01)., Conclusions: A higher nursing care level is associated with a higher incidence of blood culture contamination in the emergency department. Careful and appropriate procedures are required for patients with a higher nursing care level., Competing Interests: The authors have stated explicitly that there are no conflicts of interest in connection with this article., (© 2022 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.)

Background: We aimed to develop and externally validate a novel machine learning model that can classify CT image findings as positive or negative for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR)., Methods: We used 2,928 images from a wide variety of case-control type data sources for the development and internal validation of the machine learning model. A total of 633 COVID-19 cases and 2,295 non-COVID-19 cases were included in the study. We randomly divided cases into training and tuning sets at a ratio of 8:2. For external validation, we used 893 images from 740 consecutive patients at 11 acute care hospitals suspected of having COVID-19 at the time of diagnosis. The dataset included 343 COVID-19 patients. The reference standard was RT-PCR., Results: In external validation, the sensitivity and specificity of the model were 0.869 and 0.432, at the low-level cutoff, 0.724 and 0.721, at the high-level cutoff. Area under the receiver operating characteristic was 0.76., Conclusions: Our machine learning model exhibited a high sensitivity in external validation datasets and may assist physicians to rule out COVID-19 diagnosis in a timely manner at emergency departments. Further studies are warranted to improve model specificity., Competing Interests: All authors have completed the ICMJE uniform disclosure form. Yoshiro Kitamura and Tsubasa Goto are employees of Fujifilm Corporation. Shoji Kido is an endowed chair funded by Fujifilm Corporation. Tomohisa Baba, Tomohiro Handa, Toyohiro Hirai, Noriyuki Tomiyama, Takashi Ogura, and Kiminobu Tanizawa received research grants from FUJIFILM Corporation. Tomohiro Handa is an employee of the Collaborative Research Laboratory funded by Teijin Pharma Co., Ltd., (© 2022 Society for Clinical Epidemiology.)

Introduction: Cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) patients during the coronavirus disease 2019 (COVID-19) pandemic carries an added risk of COVID-19 infection for healthcare workers. However, because of the shortage of medical supplies and limited evidence of COVID-19 in the initial stages of the pandemic, strategies for the management of OHCA patients may have varied across hospitals., Method: A web-based questionnaire was used. The first section collected data about physician characteristics. In the second section, participants responded "Yes" or "No," if they had made changes in the areas of "personal protective equipment (PPE)" or "CPR Algorithm" for OHCA patients (these changes were the personal views of the surveyed respondents). The questionnaire was sent to the members of the Emergency Medicine Alliance mailing list. The response period was from May 22 to June 5, 2020 (the first state of emergency related to COVID-19 was declared on April 7, 2020, in Japan). Participants were asked to indicate their stress level resulting from these changes using the Likert scale ranging from 1 to 10, where 1 = "no stress" and 10 = "severe stress.", Result: A total of 110 physicians responded during the study period. The majority of participants reported changes in "PPE" (n = 106, 96.4%) and "CPR Algorithm" (n = 86, 78.2%). The reported stress level due to changes in PPE was 8 (IQR 6-9) and due to changes in the CPR algorithm, it was 7 (IQR 5-8)., Conclusion: Findings of this study suggest that physicians experienced changes in care for OHCA patients and felt stress during the initial stage of the COVID-19 pandemic. Thus, it would be better to list the actual measures that can be undertaken to prepare for any future pandemics., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Numata et al.)

Background: We developed and validated a machine learning diagnostic model for the novel coronavirus (COVID-19) disease, integrating artificial-intelligence-based computed tomography (CT) imaging and clinical features., Methods: We conducted a retrospective cohort study in 11 Japanese tertiary care facilities that treated COVID-19 patients. Participants were tested using both real-time reverse transcription polymerase chain reaction (RT-PCR) and chest CTs between January 1 and May 30, 2020. We chronologically split the dataset in each hospital into training and test sets, containing patients in a 7:3 ratio. A Light Gradient Boosting Machine model was used for the analysis., Results: A total of 703 patients were included, and two models-the full model and the A-blood model-were developed for their diagnosis. The A-blood model included eight variables (the Ali-M3 confidence, along with seven clinical features of blood counts and biochemistry markers). The areas under the receiver-operator curve of both models [0.91, 95% confidence interval (CI): 0.86 to 0.95 for the full model and 0.90, 95% CI: 0.86 to 0.94 for the A-blood model] were better than that of the Ali-M3 confidence (0.78, 95% CI: 0.71 to 0.83) in the test set., Conclusions: The A-blood model, a COVID-19 diagnostic model developed in this study, combines machine-learning and CT evaluation with blood test data and performs better than the Ali-M3 framework existing for this purpose. This would significantly aid physicians in making a quicker diagnosis of COVID-19., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE unified disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-5571/coif). Yuki Kataoka serves as an unpaid editorial board member of Annals of Translational Medicine from July 2020 to June 2022. Yuki Kataoka, Yuya Kimura, TI, YM, JM, JK, KT, HF, TH, AK, FH, SI, SF report that this study was partially supported by Kyoto University managing fund for English editing; the article processing fee was supported by the Scientific Research Works Peer Support Group (SRWS-PSG); M3 Inc. and Clinical Porter provided free Ali-M3 analysis and data storage. TI also reports that the analysis of the CT by Ali-M3 was carried out by Nobori on behalf of M3. M3 and Nobori did not know the patients’ data including the result of RT-PCR. JM also reports that receiving a lecture fee from M3 Inc. The other author has no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Introduction: It is still unclear that which anti-arrhythmics are adequate for treating refractory dysrhythmia. This study aimed to compare amiodarone and nifekalant in management of out-of-hospital cardiac arrest cases with refractory shockable rhythm., Methods: This was a post hoc analysis of cases registered in a nationwide, multicentre, prospective registry that includes 288 critical care medical centres in Japan. From June 2014 to December 2017, we included all out-of-hospital cardiac arrest patients aged ≥18 years who presented with refractory arrhythmia (sustained ventricular fibrillation or ventricular tachycardia following delivery of at least two defibrillator shocks) and treated with nifekalant or amiodarone after arrival to hospital. Overlap weight was performed to address potential confounding factors., Results: 1,317 out-of-hospital cardiac arrest patients with refractory arrhythmia were enrolled and categorized into amiodarone (n = 1,275) and nifekalant (n = 42) groups. After overlap weight was performed, there were no significant intergroup differences in increased the rate of admission after return of spontaneous circulation [-5.9% (95%CI: -7.1 to 22.4); p = 0.57], 30-day favourable neurological outcome [0.1% (95%CI: -14 to 13.9); p = 0.99], and 30-day survival [-3.9% (95% CI: -19.8 to 12.0); p = 0.63]., Conclusion: This nationwide study showed that nifekalant was not associated with improved outcomes regarding admission after return of spontaneous circulation, 30-day survival, and 30-day favourable neurological outcome compared with amiodarone., Competing Interests: The authors declare that they have no competing interests.

Ali-M3, an artificial intelligence program, analyzes chest computed tomography (CT) and detects the likelihood of coronavirus disease (COVID-19) based on scores ranging from 0 to 1. However, Ali-M3 has not been externally validated. Our aim was to evaluate the accuracy of Ali-M3 for detecting COVID-19 and discuss its clinical value. We evaluated the external validity of Ali-M3 using sequential Japanese sampling data. In this retrospective cohort study, COVID-19 infection probabilities for 617 symptomatic patients were determined using Ali-M3. In 11 Japanese tertiary care facilities, these patients underwent reverse transcription-polymerase chain reaction (RT-PCR) testing. They also underwent chest CT to confirm a diagnosis of COVID-19. Of the 617 patients, 289 (46.8%) were RT-PCR-positive. The area under the curve (AUC) of Ali-M3 for predicting a COVID-19 diagnosis was 0.797 (95% confidence interval: 0.762‒0.833) and the goodness-of-fit was P = 0.156. With a cut-off probability of a diagnosis of COVID-19 by Ali-M3 set at 0.5, the sensitivity and specificity were 80.6% and 68.3%, respectively. A cut-off of 0.2 yielded a sensitivity and specificity of 89.2% and 43.2%, respectively. Among the 223 patients who required oxygen, the AUC was 0.825. Sensitivity at a cut-off of 0.5% and 0.2% was 88.7% and 97.9%, respectively. Although the sensitivity was lower when the days from symptom onset were fewer, the sensitivity increased for both cut-off values after 5 days. We evaluated Ali-M3 using external validation with symptomatic patient data from Japanese tertiary care facilities. As Ali-M3 showed sufficient sensitivity performance, despite a lower specificity performance, Ali-M3 could be useful in excluding a diagnosis of COVID-19., Competing Interests: At the start of the study, Ali-m3 existed as a tool produced by Alibaba Damo (Hangzhou) Technology Co., Ltd for research use that had not received any approval. With the results of this study, we have confirmed that the Ali-M3 has clinical benefits. Therefore, under a special expedited review in Japan, Ali-M3 has been approved by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) and licensed for use as a diagnostic tool in actual practice. For the license in Japan, Ali-m3 should have been a commercial tool. Therefore, it was not planned that M3 Inc would benefit from the commercialization of the Ali-M3 as a result of our research for which M3 provided the Ali-M3 and storage free of charge. The authors have no patents, products in development, or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. In Japan, the M3.inc completely held the right of Ali-M3. This study was utterly free from Alibaba Damo Technology except Alibaba platform by the right of M3.inc.

Aim: Effective courses are essential for highly invasive procedures such as resuscitative endovascular balloon occlusion of the aorta. However, the coronavirus disease pandemic has forced the postponement of on-site educational courses due to transmission concerns. Few studies have examined the effectiveness of Web-based education in highly invasive procedures. To address this knowledge gap, this study aimed to investigate whether knowledge acquisition and confidence after the Web-based course are different from those acquired after the on-site course, using pre- and postcourse test scores., Methods: The increase in scores before and after the course was compared between the on-site and Web-based courses. The questions reflected knowledge about seven different topics in the course modules. In addition, participants were asked about their self-rated confidence about three topics before and after the course., Results: Thirty learners completed the on-site course, and 21 learners completed the Web-based course. Forty-seven learners completed both the precourse and postcourse tests. In both courses, the difference between the precourse and postcourse test scores showed a statistically significant increase in knowledge (on-site course: increased score, 1.8; 95% confidence interval, 0.8 to 2.8; Web-based course: increased score, 1.6, 95% confidence interval, 0.5 to 2.5). However, the difference was not statistically significant in the self-rated confidence scores about "sheath and catheter removal" among learners of the Web-based course., Conclusion: Knowledge increased significantly in both the on-site and Web-based courses. However, the Web-based course might not be sufficient to give learners confidence in the procedures., (© 2021 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background Acute decompensated heart failure (ADHF) is a life-threatening disease that requires emergent intervention. Although noninvasive positive pressure ventilation (NPPV) is crucial for treating ADHF, the earliest time point for administering NPPV remains unknown. In this study, we hypothesized that early NPPV administration for patients with acute heart failure in the emergency department (ED) would lead to a better outcome. Methodology This is a single-center retrospective cohort study at an ED of a community hospital in Japan. The data were collected from consecutive patients who were administered NPPV for ADHF in the ED from April 2016 to September 2018. The primary exposure was the timing of NPPV administration (within 30 minutes versus over 30 minutes after arrival). The primary outcome was 30-day mortality. Results A total of 115 patients were included in this study. Overall, the median age was 78 (interquartile range [IQR] = 70-84 years), and 63 (54.9%) patients were male. The median time from the arrival at the ED to NPPV administration for the patients was 14 minutes (IQR = 8-30 minutes). Overall, 72% (83/115) of the patients were categorized as early administration group (<30 minutes). The total 30-day mortality was 7.0% (8/115), and the total tracheal intubation rate was 11% (13/115). Early NPPV administration for patients with ADHF was associated with lower 30-day mortality (3.6% vs. 16%; p = 0.04) and shorter length of oxygenation (four days vs. seven days; p < 0.01). Multivariate logistic regression test showed that 30-day mortality was significantly lower in the early treatment group (adjusted odds ratio = 0.19; 95% confidential interval = 0.04-0.90). Conclusions Although further investigation is needed, early NPPV administration for patients with ADHF in the ED was associated with lower 30-day mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Nakazawa et al.)

Acute mesenteric ischemia (AMI) is a rare cause of the "acute abdomen", characterized by impaired blood flow to the intestine. The principle of treatment is restoration of perfusion to ischemic bowel and resection of any necrotic intestine. Surgery and endovascular intervention are two complementary approaches to mesenteric ischemia. Endovascular intervention is not an alternative to the surgical approach, but it has the potential to improve the prognosis of patients with AMI when judiciously combined with a surgical approach. Due to the need for emergent treatment of patients with acute mesenteric ischemia, the treatment strategy needs to be modified for each facility. This review aims to highlight cutting-edge studies and provide reasonable treatment strategies for patients with acute mesenteric ischemia based on available evidence., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines., Competing Interests: Financial and academic COIs as well as the role(s) of each committee member are disclosed in the additional file 1 (https://www.jsicm.org/pdf/guidelineEN/Additionalfile1.pdf). Financial COIs were disclosed in accordance with the standards used by the Japanese Association of Medical Sciences from 2017 through 2019., (© 2021 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)