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Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a central kinase involved in energy homeostasis. Increased intracellular AMP levels result in AMPK activation through the binding of AMP to the γ-subunit of AMPK. Recently, we reported that AMP-induced AMPK activation is impaired in the kidneys in chronic kidney disease (CKD) despite an increase in the AMP/ATP ratio. However, the mechanisms by which AMP sensing is disrupted in CKD are unclear. Here, we identified mechanisms of energy homeostasis in which Unc-51-like kinase 1 (ULK1)-dependent phosphorylation of AMPKγ1 at Ser260/Thr262 promoting AMP sensitivity of AMPK. AMPK activation by AMP was impaired in Ulk1 knockout mice despite an increased AMP/ATP ratio. ULK1 expression is markedly downregulated in CKD kidneys, leading to AMP sensing failure. Additionally, MK8722, an allosteric AMPK activator, stimulated AMPK in the kidneys of a CKD mouse model (5/6th nephrectomy) via a pathway that is independent of AMP sensing. Thus, our study shows that MK8722 treatment significantly attenuates the deterioration of kidney function in CKD and may be a potential therapeutic option in CKD therapeutics., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Moderately differentiated neuroendocrine tumors of the larynx are rare malignant tumors that arise from the submucosa of the larynx, for which surgery is the first-line treatment., Presentation of Case: We report a case of moderately differentiated neuroendocrine tumor of the larynx, in which the patient, a 74-year-old man, experienced long-term palliation but an unfortunate outcome of death owing to metastasis. Laryngeal endoscopic examination revealed an elevated submucosal lesion on the laryngeal surface of the epiglottis. Computed tomography and magnetic resonance imaging showed a tumor-like lesion demonstrating a contrasting effect in the submucosa of the epiglottis. A biopsy revealed a moderately differentiated neuroendocrine tumor (formerly called an atypical carcinoid), and a horizontal partial laryngectomy was performed. The patient had a good postoperative course; however, three years and ten months after surgery, he experienced recurrence in the upper gastrointestinal tract and carcinoid syndrome and died four years and three months after the surgery., Discussion: The prognosis of laryngeal neuroendocrine tumors remains poor. In this case, local control was possible without irradiation because the resection margins were negative on pathological examination. This case report has been reported in line with the SCARE Criteria., Conclusion: Long-term follow-up of this type of tumor is necessary, as distant metastasis is likely to affect prognosis. In addition to surgery, effective adjuvant therapies, including molecular targeted therapies, should be established., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bipolar disorder, a psychiatric condition identified by significant mood changes and a considerable genetic connection with schizophrenia, needs continuous and extensive management due to its common onset in adolescence and significant impact on psychosocial activities. While traditional mood stabilizers continue to be widely used, the pursuit of more effective treatments remains ongoing, with the current research targeting various stages of the disorder. This study provides a thorough examination of new pharmacological treatments for bipolar disorder, which are currently in Phase II and Phase III clinical trials up to 22 April 2024. A systematic search was conducted using the NIH National Library of Medicine, focusing on both repurposed and innovative drugs now in advanced stages of testing. The study identifies several promising therapeutic agents, including those intended for severe mood disorders with suicidal tendencies, and others aimed at treating mood-related neuroinflammation. Drugs that enhance dopamine stabilization and those that act on serotonin receptor activities were found notable. We also explored the strategic repurposing of already existing medications for broader therapeutic uses and looked into the potential of new formulations designed for the immediate management of symptoms. Our analysis highlights two main strategies for tackling bipolar disorder: finding new uses for existing drugs and developing new medications with unique actions. This approach shows continuous improvement in drug treatments, helping patients manage their condition better and addressing the complicated nature of bipolar disorder., Competing Interests: Declaration of competing interest The authors declare the following interests over the past 3 years. Nishida received speaker's honoraria from Otsuka Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Viatris. Inc., Osaka is a former employee of Otsuka Pharmaceutical Co., Ltd. Kanazawa has received speaker's honoraria Teijin-Pharma Co., Ltd, Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., EA Pharma Co., Ltd, Eisai Co., Ltd., Janssen Pharmaceutical K.KLundbeck, Meiji Seika Pharma Co., Ltd., MSD K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Viatris Inc., Teijin Pharmaceutical Co., Ltd., and grants from Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd, and Sumitomo Dainippon Pharma Co., Ltd., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A 71-year-old woman developed nephrotic syndrome during 10-year follow-up for chronic lymphocytic leukemia. A renal biopsy sample analysis revealed IgG1-lambda-positive monoclonal immunotactoid glomerulopathy (mITG). The patient was treated with ibrutinib, a Bruton tyrosine kinase inhibitor, and complete renal remission was achieved after 24 months. ITG is a rare disease that is characterized by glomerular deposition. In particular, mITG, which presents immune deposits that exhibit light-chain restriction, is often associated with hematologic disorders. Most patients with mITG receive immunosuppressive therapy and/or chemotherapy; however, to our knowledge, there have been no reports of treatment with ibrutinib.

Regional cerebral oxygen saturation (ScO 2 ) determined by near-infrared spectroscopy, monitoring both arterial and venous blood oxygenation of the brain, could reflect the balance between oxygen delivery and consumption. The aim of this study was to determine the predictabilities of ScO 2 and estimated oxygen extraction ratio (eO 2 ER) with outcomes in infants with congenital heart disease (CHD). This study was a two-center, retrospective study of patients at 12 months of age or younger with CHD who underwent cardiac surgery. The primary outcome was a composite of one or more major adverse events (MAEs) after surgery: death from any cause, circulatory collapse that needed cardiopulmonary resuscitation, and requirement for extracorporeal membrane oxygenation. Based on the assumptions of arterial to venous blood ratio, eO 2 ER was calculated. A total of 647 cases were included in this study. MAEs occurred in 16 patients (2.5%). There were significant differences in post-bypass ScO 2 [46.61 (40.90, 52.05) vs. 58.52 (51.52, 66.08), p < 0.001] and post-bypass eO 2 ER [0.66 (0.60, 0.78) vs. 0.52 (0.43, 0.61), p < 0.001] between patients with MAEs and patients without MAEs. Area under the receiver operating curve (AUROC) of post-bypass ScO 2 was 0.818 (95% confidence interval: 0.747-0.889), AUROC of post-bypass eO 2 ER was 0.783 (0.697-0.870) and AUROC of post-bypass maximum serum lactate level was 0.635 (0.525-0.746). Both ScO 2 and eO 2 ER, especially after weaning off bypass, are acceptable predictive markers for predicting MAEs after cardiac surgery in infants.(227 words)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mucosa-associated lymphoid tissue (MALT) lymphoma commonly arises from chronic inflammation or autoimmune diseases, such as Sjögren syndrome (SjS). Although rare, amyloid deposition in MALT lymphoma has been reported. We present a rare case of parotid gland MALT lymphoma in a 49-year-old woman, in whom preoperative diagnosis was challenging due to atypical imaging findings resulting from amyloid deposits. MRI showed T2-hypointense and T1-iso- to slightly hyperintense masses in the left parotid gland and right sublingual gland, with predominant marginal contrast enhancement and no significant diffusion restriction. Additionally, atrophy and fatty replacement of the parenchyma were noted in bilateral parotid glands, suggesting SjS. Left superficial parotidectomy was performed and pathological findings confirmed MALT lymphoma with extensive amyloid deposition. Histopathological findings of the resected parotid gland parenchyma also suggested SjS. MALT lymphoma should be considered in the differential diagnosis of multiple salivary gland masses in patients with suspected SjS. If MRI reveals atypical imaging findings for malignant lymphoma, particularly T2-hypointensity with no significant diffusion restriction, the possibility of amyloid deposition in MALT lymphoma should be considered., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Radiotherapy is one of the definitive treatments for head and neck squamous cell carcinoma, especially early-stage glottic squamous cell carcinoma. Although there are several studies on the initiation weekday of cancer treatment, there are very few studies in the radiotherapy field. Thus, the present study investigated whether the initiation weekday of radiotherapy affects the local control rate for stage 1 glottic squamous cell carcinoma. A total of 105 patients with stage 1 glottic squamous cell carcinoma underwent definitive radiotherapy alone between 2007 and 2021. The group in which radiotherapy was started between Monday and Wednesday was compared with the group in which radiotherapy was started on Thursday or Friday. Sixty-seven patients started radiotherapy between Monday and Wednesday and 38 on Thursday or Friday. The 5-year local control rate was 98% (95% confidence interval: 94-100%) in the Monday-Wednesday group and 83% (95% confidence interval: 71-96%) in the Thursday-Friday group, with a significant difference (P = 0.005). On multivariate analysis including age, overall administration time (days), fractionation, irradiation field size and initiation weekday of radiotherapy, no factors other than initiation weekday affecting local control were identified. Radiotherapy toxicity did not differ between the two groups. For stage 1 glottic squamous cell carcinoma, starting radiotherapy on Thursday or Friday is associated with a lower local control rate; therefore, radiotherapy should be started by Wednesday., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The purpose of this study is to investigate whether preoperative intubation simulation using custom-made simulator is useful during anesthesia induction for the children who have difficult airway. We included the children under 15 years of age who have difficult airway which had been already known. Prior to the scheduled surgery, CT imaging was performed and a 3D reconstruction of the face from the chest was performed. Then custom-made airway simulator was made. We tried to intubate custom-made simulator of patients preoperatively. We planned how to intubate the patient for anesthesia induction from the result of intubation simulation. The findings of direct laryngoscopy were compared with the findings during intubation. Three patients were included in this study. It took up to 3 weeks to create a simulator, which was difficult due to time constraints to accommodate emergency surgeries. Simulation findings correlated well with findings during anesthesia induction. There were no cases of severe hypotension or hypoxia during induction of anesthesia with the planned intubation method. In conclusion, preoperative intubation simulation using custom-made simulator may be useful for the patients who have difficult airway., (© 2024. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Background: Delirium frequently affects the consciousness of the elderly, particularly those in hospitals. Evidence increasingly associates linking delirium history to an increased risk of dementia. However, most studies are limited in scope, focusing mainly on postoperative or intensive care units with small patient samples, which affects the broader applicability of their findings., Aims: To elucidate the precise incidence of delirium and the subsequent onset of dementia within whole inpatients. Additionally, we aimed to explore the correlation between the emergence of delirium during hospitalization and the subsequent manifestation of dementia., Design Setting and Participants: We conducted a retrospective cohort analysis employing a decade-long electronic medical record dataset consisted of 261,123 patients in Osaka Medical and Pharmaceutical University Hospital. Key analyses were performed October 2022 to January 2023., Main Outcomes and Measures: The primary outcome, dementia onset, was determined by prescriptions for the anti-dementia drugs donepezil, galantamine, memantine, or rivastigmine, which are approved for use in Japan., Results: 10,781 patients met the inclusion criteria. The median interval between the onset of dementia was 972.5 days for individuals without a history of delirium, whereas for those with a history of delirium, it was notably shorter at 592.5 days. This disparity culminated in a hazard ratio of 5.29 (95% confidence interval: 1.35-20.75) for subsequent dementia onset., Conclusions and Relevance: This investigation underscores the imperative significance of directing attention toward preventive measures against delirium during hospitalization, alongside the necessity of diligent monitoring and intervention for cognitive decline in patients who encounter delirium., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Minami, Toyoda, Hata, Nishihara, Neo, Nishida and Kanazawa.)

Objective: To compare the incidence of hypotension between remimazolam and sevoflurane under general anesthesia for cardiac catheterization in patients with congenital heart disease., Design: Retrospective observational study., Setting: A single university hospital with 300 pediatric cardiac catheterizations by general anesthesia performed annually., Participants: Patients younger than 15 years who underwent cardiac catheterization under general anesthesia between March 1, 2021, and December 31, 2022. Exclusion criteria were general anesthesia maintained with other than remimazolam or sevoflurane, receipt of remifentanil, American Society of Anesthesiologists score 4 or 5, emergency procedures, and no direct arterial pressure measurement., Interventions: General anesthesia was maintained with remimazolam or sevoflurane., Measurements and Main Results: A total of 309 patients were analyzed, including 28 in the remimazolam group and 281 in the sevoflurane group. Propensity score matching adjusted for confounding factors resulted in 28 patients in each arm, with no apparent differences in background factors. Hypotension was defined as a time-averaged area > 1, in which systolic arterial pressure fell below 80% of the baseline from the start of anesthesia to the end of procedure. The significance level was set at P < .05. The incidence of hypotension was 39.3% in the remimazolam arm and 46.4% in the sevoflurane arm, with no significant difference (P = .79), although the ratio of the median systolic arterial pressure to the baseline value was significantly higher in the remimazolam arm (91.4 ± 15.2% vs 83.2 ± 11.4% in the sevoflurane arm; P = .03)., Conclusions: Remimazolam was not associated with a lower incidence of hypotension compared to sevoflurane during pediatric cardiac catheterization for congenital heart disease while maintaining significantly higher blood pressure overall., 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 © 2024 Elsevier Inc. All rights reserved.)

Aim: The pathophysiological mechanisms of postoperative delirium (POD) are still unclear, and there is no reliable biomarker to distinguish between those with and without POD. Our aim was to discover DNAm markers associated with POD in blood collected from patients before and after gastrointestinal surgery., Method: We collected blood samples from 16 patients including 7 POD patients at three timepoints; before surgery (pre), the first and third postoperative days (day1 and day3). We measured differences in DNA methylation between POD and control groups between pre and day1 as well as between pre and day3 using the Illumina EPIC array method. Besides, enrichment analysis with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms were also performed after excluding influence of common factors related to surgery and anesthesia., Result: The results showed that pre and day1 comparisons showed that immune and inflammatory signals such as 'T-cell activation' were significantly different, consistent with our previous studies with non-Hispanic White subjects. In contrast, we found that these signals were not significant any more when pre was compared with day3., Conclusion: These results provide strong evidence for the involvement of inflammatory and immune-related epigenetic signals in the pathogenesis of delirium, including POD, regardless of ethnic background. These findings also suggest that DNAm, which is involved in inflammation and immunity, is dynamically altered in patients with POD. In summary, the present results indicate that these signals may serve as a new diagnostic tool for POD., Competing Interests: Declaration of competing interest Gen Shinozaki has pending patents “Epigenetic Biomarker of Delirium Risk” in the PCT Application No. PCT/US19/51276, in the PCT Application No. PCT/US21/63166, and in U.S. Provisional Patent No. 62/731599. All other authors have declared that no conflict of interest exists., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lipid nanoparticles (LNPs) have recently been used as nanocarriers in drug delivery systems for nucleic acid drugs. Their practical applications are currently primarily limited to the liver and specific organs. However, altering the type and composition ratio of phospholipids improves their distribution in organs other than the liver, such as the spleen and lungs. This study aimed to elucidate the effects of LNP components and particle size on in vivo distribution through systemic circulation to pancreatic islets to achieve better targeting of islets, which are a fundamental therapeutic target for diabetes. Fluorescence-labeled LNPs were prepared using three phospholipids: 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), with particle sizes of 30-160 nm (diameter) using a microfluidic device. Baffled-structured iLiNP devices with adjusted flow-rate ratios and total flow rates were used. After the intravenous administration of LNPs to C57BL/6 J mice, the distribution of each LNP type to the major organs, including the pancreas and pancreatic islets, was compared using ex vivo fluorescence imaging and observation of pancreatic tissue sections. DSPC-LNPs- and DOPE-LNPs showed the highest distribution in the spleen and liver, respectively. In contrast, the DOPC-LNPs showed the highest distribution in the pancreas and the lowest distribution in the liver and spleen. In addition, smaller particles showed better distribution throughout the pancreas. The most significant LNP distribution in the islets was observed for DOPC-LNPs with a particle size of 160 nm. Furthermore, larger LNPs tended to be distributed in the islets, whereas smaller LNPs tended to be distributed in the exocrine glands. DOPC-LNPs were distributed in the islets at all cholesterol concentrations, with a high distribution observed at >40% cholesterol and > 3% PEG and the distribution was higher at 24 h than at 4 h. Thus, LNP composition and particle size significantly affected islet distribution characteristics, indicating that DOPC-LNPs may be a drug delivery system for effectively targeting the pancreas and islets., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gastric cancer is one of the most common cancers worldwide, and new therapeutic strategies are urgently needed. Ferroptosis is an intracellular iron-dependent cell death induced by the accumulation of lipid peroxidation, a mechanism different from conventional apoptosis and necrosis. Therefore, induction of ferroptosis is expected to be a new therapeutic strategy. Glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) have been identified as the major inhibitors of ferroptosis. Herein, we performed immunohistochemistry for GPX4, FSP1, and 4-HNE using tissues from patients with gastric cancer and investigated the relationship between these factors and prognosis. Patients with high GPX4 expression or high GPX4 expression and low 4-HNE accumulation tended to have a poor prognosis ( p = 0.036, 0.023), whereas those with low FSP1 expression and high 4-HNE accumulation had a good prognosis ( p = 0.033). The synergistic induction of cell death by inhibiting GPX4 and FSP1 in vitro was also observed, indicating that the cell death was non-apoptotic. Our results indicate that the expression and accumulation of lipid peroxidation-related factors play an important role in the clinicopathological significance of gastric cancer and that novel therapeutic strategies targeting GPX4 and FSP1 may be effective in treating patients with gastric cancer who have poor prognosis.

A subset of clear cell renal cell carcinomas (ccRCCs) exhibits various growth patterns that infiltrate the normal renal parenchyma; however, our understanding of its association with cancer aggressiveness is incomplete. Here, we show that the morphology of the tumor interface with normal renal parenchyma is robustly associated with cancer recurrence after surgery, even when compared with the TNM staging system or the World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grade in nonmetastatic ccRCC. Hematoxylin and eosin-stained slides of whole tissue sections from surgical specimens were analyzed using a cohort of 331 patients with nonmetastatic ccRCC treated with radical nephrectomy. The patients were classified into 10 subgroups based on our classification algorithms for assessing the tumor interface with normal renal parenchyma. Among the 10 subgroups, 4 subgroups consisting of 40 patients (12%) were identified to have aggressive forms of nonmetastatic ccRCC associated with poor prognosis and unified as renal parenchymal infiltration or micronodular spread (RPI/MNS) phenotypes. Multivariable analyses showed that RPI/MNS phenotypes were robustly associated with shorter disease-free survival, independently of existing pathological factors including the TNM staging system and WHO/ISUP nuclear grade. The hazard ratio was highest for RPI/MNS (4.62), followed by WHO/ISUP grades 3 to 4 (2.11) and ≥pT3a stage (2.05). In addition, we conducted genomic analyses using next-generation sequencing of infiltrative lesions in 18 patients with RPI/MNS and tumor lesions in 33 patients without RPI/MNS. Results showed that alterations in SETD2 and TSC1 might be associated with RPI/MNS phenotypes, whereas alterations in PBRM1 might be associated with non-RPI/MNS phenotypes. These data suggest that RPI/MNS may be associated with aggressive genomic backgrounds of ccRCC, although more comprehensive analyses with a larger sample size are required. Future studies may further elucidate the clinical implications of RPI/MNS, particularly for deciding the indication of adjuvant treatment after nephrectomy., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Advanced neuroendocrine carcinoma (NEC) has an extremely poor prognosis, partly explained by the rarity and diagnostic difficulty, for which the most appropriate treatment strategy has not been established. In this report, we discuss a case of unresectable advanced esophagogastric junction NEC, which was difficult to diagnose, that has achieved relatively long-term survival with multidisciplinary treatment centered on nivolumab. A man in his 60s was initially diagnosed with an advanced esophagogastric junction squamous cell carcinoma (SCC). The lymph node metastasis was detected in the regional lymph nodes and para-aortic region. We diagnosed the patient with T3, N3, M1 (Lym), stage IVB, and administered systemic chemotherapy. Due to the failure of first-line, fluorouracil, and cisplatin therapy, we administered nivolumab as the second-line therapy. This therapy demonstrated partial response, so we performed conversion surgery, however the postoperative diagnosis was NEC. Three years after treatment initiation, a single lymph node metastasis has recurred, which is under control with nivolumab and radiation therapy. However, 4.5 years after the start of treatment, with the advent of immune-related adverse events (irAE), nivolumab was discontinued and the patient was placed on surveillance. Six months after that, metastasis to the hilar lymph node and adrenal gland was observed. Both times that recurrence/metastasis appeared, they occurred while nivolumab was being discontinued, suggesting its significant systemic anti-cancer effect. Therefore, nivolumab in particular may be an effective treatment for advanced esophageal NEC, and this case suggests that it may contribute to prolonged progression-free survival., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. 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, Hanzawa et al.)

Controlling pulmonary blood flow in patients who have undergone Norwood palliation, especially early postoperatively, is challenging due to a change in the balance of systemic and pulmonary vascular resistance. We applied a combination therapy of clipping and balloon angioplasty for right ventricle-pulmonary artery (RV-PA) shunt to control pulmonary blood flow, but the influence of the combination therapy on the PA condition is uncertain. Retrospectively analysis was conducted of all infants with hypoplastic left heart syndrome who had undergone Norwood palliation with RV-PA shunt at Okayama University Hospital from January 2008 to September 2022. A total of 50 consecutive patients underwent Norwood palliation with RV-PA shunt in this study period. Of them, 29 patients underwent RV-PA shunt flow clipping, and the remaining 21 had unclipped RV-PA shunt. Twenty-three patients underwent balloon angioplasty for RV-PA shunt with clips. After balloon angioplasty, oxygen saturation significantly increased from 69 (59-76)% to 80 (72-86)% (p < 0.001), and the narrowest portion of the clipped conduit significantly improved from 2.8 (1.8-3.4) to 3.8 (2.9-4.6) mm (p < 0.001). In cardiac catheterizations prior to Bidirectional cavo-pulmonary shunt (BCPS), there were no significant differences in pulmonary-to-systemic flow ratio (Qp/Qs), ventricular end-diastolic pressure, Nakata index, arterial saturation, mean pulmonary artery pressure and pulmonary vascular resistance index. On the other hand, in Cardiac catheterizations prior to Fontan, Nakata index was larger in the clipped group (p = 0.02). There was no statistically significant difference in the 5-year survival between the two groups (clipped group 96%, unclipped group 74%, log-rank test: p = 0.13). At least, our combination therapy of clipping and balloon angioplasty for RV-PA shunt did not negatively impact PA growth. Although there is a trend toward better but not statistically significant difference in outcomes in the clipped group compared to the non-clipped group, this treatment strategy may play an important role in improving outcomes in hypoplastic left heart syndrome., (© 2024. The Author(s).)

We study the microrheology of active suspensions through direct hydrodynamic simulations using model pusher-like microswimmers. We demonstrate that the friction coefficient of a probe particle is notably reduced by hydrodynamic interactions (HIs) among a moving probe and the swimmers. When a swimmer approaches a probe from the rear (front) side, the repulsive HIs between them are weakened (intensified), which results in a slight front-rear asymmetry in swimmer orientation distribution around the probe, creating a significant additional net driving force acting on the probe from the rear side. The present drag-reduction mechanism qualitatively differs from that of the viscosity-reduction observed in sheared bulk systems and depends on probing details. This study provides insights into our fundamental knowledge of hydrodynamic effects in active suspensions and serves as a practical example illuminating distinctions between micro- and macrorheology measurements.

Delirium is risky and indicates poor outcomes for patients. Therefore, it is crucial to create an effective delirium detection method. However, the epigenetic pathophysiology of delirium remains largely unknown. We aimed to discover reliable and replicable epigenetic (DNA methylation: DNAm) markers that are associated with delirium including post-operative delirium (POD) in blood obtained from patients among four independent cohorts. Blood DNA from four independent cohorts (two inpatient cohorts and two surgery cohorts; 16 to 88 patients each) were analyzed using the Illumina EPIC array platform for genome-wide DNAm analysis. We examined DNAm differences in blood between patients with and without delirium including POD. When we compared top CpG sites previously identified from the initial inpatient cohort with three additional cohorts (one inpatient and two surgery cohorts), 11 of the top 13 CpG sites showed statistically significant differences in DNAm values between the delirium group and non-delirium group in the same directions as found in the initial cohort. This study demonstrated the potential value of epigenetic biomarkers as future diagnostic tools. Furthermore, our findings provide additional evidence of the potential role of epigenetics in the pathophysiology of delirium including POD., (© 2024. The Author(s).)

Maxillary angiosarcoma, an aggressive tumor derived from vascular endothelial cells, is very rare. Recently, antivascular endothelial growth factor (VEGF) therapies have attracted considerable attention. We describe the clinical course of a patient with maxillary angiosarcoma and discuss the expression of VEGF signaling molecules assessed via immunohistological analysis. An 81-year-old man presented with an aggressive tumor in the left maxillary sinus. Biopsy revealed atypical nuclear cell proliferation, and the tumor was suspected to be a sarcoma. The maxillary malignancy was treated using a multidisciplinary approach with a combination of surgery, radiotherapy, and regional chemotherapy. Examination of the specimen obtained in the first surgery revealed maxillary angiosarcoma, found to be positive for CD31, while negative for CD34, D2-40, and factor Ⅷ. Although no pathological residual tumor was observed after the planned wide surgery, cervical lymph node and distant metastases occurred. The patient died 24 months after the first surgery. Staining revealed VEGF receptor (VEGFR) 1, VEGFR2, phosphorylated Ak strain transforming, mitogen-activated protein kinase, and signal transducer and activator of transcription 3 positivity. Although our findings do not indicate that anti-VEGF therapy is beneficial for treating maxillary angiosarcomas, we found that VEGFR signaling pathways were activated in maxillary angiosarcomas similar to angiosarcomas originating at other sites. Herein, we report a case of maxillary angiosarcoma, focused on VEGFR and signaling pathway activation. To our knowledge, this is the first report to describe VEGFR system immunostaining findings in maxillary angiosarcoma., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Although the effects of exercise training (ET) on sleep problem have been reported, the effects according to the components of exercise, including intensity, frequency, and time window, are unknown. Thus, in this study, we aimed to assess the effects of ET on sleep quality in community-dwelling older adults with sleep problems., Methods: We evaluated individuals aged ≥65 years whose Pittsburgh sleep quality index was >5 points at baseline. The participants were allocated to either the control group or the ET group and underwent interval walking training (IWT) for 5 months. Information regarding intensity, frequency, and time window of ET were obtained using a waist-worn accelerometer., Results: Overall, 63 participants (24 men [mean ± standard deviation age: 75.1 ± 4.6 years] and 39 women [74.7 ± 5.2 years]) and 65 participants (24 men [75.2 ± 4.0 years] and 41 women [73.6 ± 4.2 years]) were included in the ET and control groups, respectively. The change in Pittsburgh sleep quality index was not significantly different between the two groups for both sexes. In the ET group, women who exercised 3-8 h before bedtime, men who did ET > 8 h before bedtime and more than 1 h after waking up, and men who did ET ≥ 5.05 days/week experienced significant improvements compared to the baseline., Conclusions: IWT does not significantly improve sleep quality. To obtain improvements in sleep quality, it might be necessary to consider the time window of performing ET for both sexes and ET frequency for men., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kuniyasu Kamiya reports financial support was provided by The Meiji Yasuda Life Foundation of Health and Welfare. Junko Tamaki reports financial support was provided by The Ministry of Education, Culture, Sports, Science. If there are other authors, they 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 © 2024 Elsevier B.V. All rights reserved.)

This study registered consecutive cases to elucidate the efficacy of rTMS treatment for depression within the Japanese public health insurance system. Of the 102 patients with depression who received rTMS over the left dorsolateral prefrontal cortex, 44 (43.1 %) patients reached remission and 14 (13.7 %) patients did not reach remission but responded to treatment. No serious adverse events occurred. Low baseline HAMD-17 score was associated with remission after rTMS treatment. Favorable outcomes of rTMS treatment were shown in this cohort within the Japanese public insurance system. Our results provide insights into rTMS treatment for depression in real-world clinical setting., Competing Interests: Declaration of Competing Interest Authors Imazu, Ikeda, Shinosaki, and Takahashi have received speaker honoraria from Teijin Pharma Limited. Author Kanazawa has received materials supervision fee from Teijin Pharma Limited., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The development of a highly active photocatalyst for visible-light water splitting requires a high-quality semiconductor material and a cocatalyst, which promote both the migration of photogenerated charge carriers and surface redox reactions. In this work, a cocatalyst was loaded onto an oxyfluoride photocatalyst, Pb 2 Ti 2 O 5.4 F 1.2 , to improve the water oxidation activity. Among the metal oxides examined as cocatalysts, RuO 2 was found to be the most suitable, and the O 2 evolution activity depended on the preparation conditions for Ru/Pb 2 Ti 2 O 5.4 F 1.2 . The highest activity was obtained with RuCl 3 -impregnated Pb 2 Ti 2 O 5.4 F 1.2 heated under a flow of H 2 at 523 K. The H 2 -treated Ru/Pb 2 Ti 2 O 5.4 F 1.2 showed an O 2 evolution rate an order of magnitude higher than those for the analogues without the H 2 treatment (e. g., RuO 2 /Pb 2 Ti 2 O 5.4 F 1.2 ). Physicochemical analyses by X-ray absorption fine-structure spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and time-resolved microwave conductivity measurements indicated that the optimized photocatalyst contained partially reduced RuO 2 species with a particle size of ~5 nm. These partially reduced species effectively trapped the photogenerated charge carriers and promoted the oxidation of water into O 2 . The optimized Ru/Pb 2 Ti 2 O 5.4 F 1.2 could function as an O 2 -evolving photocatalyst in Z-scheme overall water splitting, in combination with an Ru-loaded, Rh-doped SrTiO 3 photocatalyst., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

In this study, we investigated the effects of various disinfectants used to prevent infectious diseases on medical images and medical equipment. First, we investigated the effect of residual disinfectant on medical images in CT, mammography (MMG), and general imaging systems. Acrylic discs with various disinfectants attached were photographed using each imaging device, and visual evaluation and changes in image signal values were evaluated. We also conducted a questionnaire survey of each manufacturer regarding cleaning methods for medical devices. With CT/MMG, residual disinfectant could be visually confirmed on the image. Although this could not be confirmed with the general imaging system, a significant difference was confirmed in the image signal values of the general imaging system through statistical analysis. This is thought to be largely due to the influence of nonlinearity in the short-time imaging range of general imaging equipment. In addition, from the responses to a questionnaire survey of each medical device manufacturer, we were able to understand detailed cleaning methods that are not covered in medical device instruction manuals.

Eomesodermin-expressing (Eomes + ) T-helper (Th) cells show cytotoxic characteristics in secondary progressive multiple sclerosis. We found that Eomes + Th cell frequency was increased in the peripheral blood of amyotrophic lateral sclerosis and Alzheimer's disease patients. Furthermore, granzyme B production by Th cells from such patients was high compared with controls. A high frequency of Eomes + Th cells was observed in the initial (acutely progressive) stage of amyotrophic lateral sclerosis, and a positive correlation between Eomes + Th cell frequency and cognitive decline was observed in Alzheimer's disease patients. Therefore, Eomes + Th cells may be involved in the pathology of amyotrophic lateral sclerosis and Alzheimer's disease. ANN NEUROL 2024;95:1093-1098., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia. In Japan, its use requires management by a blood monitoring system called the Clozaril Patient Monitoring Service (CPMS) for the early detection of serious side effects such as agranulocytosis, which is extremely rare. Monitoring services vary among the clozapine suppliers in different countries. Additionally, Japanese patients can be started on clozapine treatment exclusively through an 18-week inpatient admission at a psychiatric hospital capable of coordinating with a hematologist. One reported reason for the lack of widespread clozapine use in Japan is the difficulty in establishing collaboration with hematologists when agranulocytosis/leukopenia occurs. Hence, we conducted a nationwide web-based survey of CPMS-registered psychiatric facilities in Japan to determine the status of collaboration with hematology departments. Valid responses were received from the psychiatrists responsible for prescribing clozapine at 203 of the 547 facilities (response rate: 37.1 %). The largest number of psychiatric facilities (61 %) collaborated with hematologists at another facility with a psychiatry department, while psychiatrists in 32 % of the facilities worked with hematologists at their own facilities. Most patients with clozapine-induced agranulocytosis/leukopenia could be treated with clozapine discontinuation and follow-up in psychiatric inpatient units with the assistance of a hematologist. The actual workload of hematologists was limited, and the patients might experience the burden of repeated blood sampling. This study suggests that disseminating information regarding the status of collaborations with hematologists may promote the widespread use of clozapine in Japan. SHORT COMMENT FOR TWITTER: This study suggests that most patients with clozapine-induced agranulocytosis/leukopenia could be treated with clozapine discontinuation and follow-up in psychiatric inpatient units with the assistance of a hematologist., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Circulating microRNAs (miRNAs) were investigated as biomarkers for the diagnosis of early pregnancy in cattle. The levels of prospective miRNA biomarkers and the features of extracellular vesicles (EVs) in the blood were evaluated. In Study 1, plasma samples from cows 21 days after artificial insemination (AI) were examined using RT-qPCR to determine the levels of seven circulating miRNAs. Only the levels of miR-126-3p were significantly lower in the pregnant group than in the non-pregnant group. In Study 2, among individuals not pregnant at the first AI, the miRNA levels were compared between the individuals pregnant at the second AI and those who remained non-pregnant. The miR-25 levels were significantly higher in the pregnant group at the second AI than in the pregnant group at the first AI; miR-19b, miR-27b, and miR-29a levels were also high. In the non-pregnant group, changes were absent in the miRNA levels in the same individual between the first and second AIs. In Study 3, Western blotting and RT-qPCR showed the presence of miRNAs in EVs and their levels were lower than in plasma. Thus, circulating miR-126-3p may serve as a biomarker for the diagnosis of early pregnancy in cattle. In addition, the expression of some miRNAs tended to be higher during pregnancy than during non-pregnancy in the same individual, suggesting their potential as an index to determine pregnancy and non-pregnancy rates using a comparative method.

Background: Although an increasing number of studies have reported the usefulness of early minimally invasive surgery (MIS) or fragility fracture of the pelvis (FFP), MIS is difficult to perform in every hospital, partly because of equipment problems. Moreover, different opinions exist on FFP treatment methods and the indication for surgery is usually determined by the fracture type. Since our hospital follows a conservative approach as the basic treatment, this study examined the outcomes of such an FFP approach., Hypothesis: FFP outcomes are influenced by the fracture type and walking ability before the injury., Patients and Methods: We investigated the bone fusion rate, bone fusion duration, unloading duration, walking ability trends, and outcomes in 76 patients with FFP treated conservatively at our hospital., Results: The union rate, mean period until union, and follow-up period were 93.4%, 3.3 months, and 14.3 months, respectively. Walking ability significantly decreased from 5.1 points before the injury to 4.4 points during the last follow-up (p<0.01). The average unloading period was 12.8 days, and FFPs showed a high bone fusion rate, even with conservative treatment., Discussion: Most patients eventually returned to their pre-injury status despite slightly decreased walking ability. Given the invasive nature of surgery, the indications for surgery should be carefully assessed after considering the risk-benefit ratio., Level of Evidence: III; retrospective study., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Aim: Live two-way video, easily accessible from home via smartphones and other devices, is becoming a new way of providing psychiatric treatment. However, lack of evidence for real-world clinical setting effectiveness hampers its approval by medical insurance in some countries. Here, we conducted the first large-scale pragmatic, randomized controlled trial to determine the effectiveness of long-term treatment for multiple psychiatric disorders via two-way video using smartphones and other devices, which are currently the primary means of telecommunication., Methods: This randomized controlled trial compared two-way video versus face-to-face treatment for depressive disorder, anxiety disorder, and obsessive-compulsive disorder in the subacute/maintenance phase during a 24-week period. Adult patients with the above-mentioned disorders were allocated to either a two-way video group (≥50% video sessions) or a face-to-face group (100% in-person sessions) and received standard treatment covered by public medical insurance. The primary outcome was the 36-Item Short-Form Health Survey Mental Component Summary (SF-36 MCS) score. Secondary outcomes included all-cause discontinuation, working alliance, adverse events, and the severity rating scales for each disorder., Results: A total of 199 patients participated in this study. After 24 weeks of treatment, two-way video treatment was found to be noninferior to face-to-face treatment regarding SF-36 MCS score (48.50 vs 46.68, respectively; p < 0.001). There were no significant differences between the groups regarding most secondary end points, including all-cause discontinuation, treatment efficacy, and satisfaction., Conclusion: Two-way video treatment using smartphones and other devices, was noninferior to face-to-face treatment in real-world clinical settings. Modern telemedicine, easily accessible from home, can be used as a form of health care., (© 2023 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Purpose: The aims of this study were (1) to determine the associations of cardioplegic solutions with postoperative main strong ion difference (mSID), which is the difference between sodium ion concentration and chloride ion concentration ([Cl - ]) and (2) to determine the associations of cardioplegic solutions with markers of organ dysfunction., Methods: In this retrospective cohort study, patients aged <5 years who underwent cardiac surgery in a tertiary teaching hospital were included. Patients were classified on the basis of the type of cardioplegic solution: modified del Nido cardioplegia (mDNC) and conventional cardioplegia (CC). The effects of mDNC on postoperative mSID and markers of organ functions were examined using propensity-matched analysis., Results: A total of 500 cases were included. mDNC solution was used in 163 patients (32.6%). After propensity score matching, patients in the mDNC group (n = 152) had significantly higher minimum mSID [28 (26, 30) mEq/L vs. 27 (25, 29) mEq/L, p = 0.02] and lower maximum [Cl - ] [112 (109, 114) mEq/L vs. 113 (111, 117) mEq/L, p < 0.001] than patients in the CC group (n = 304). The incidences of low mSID and hyperchloremia in the mDNC group were significantly lower than those in the CC group (63.8 vs. 75.7%, p = 0.01 and 63.2 vs. 79.3%, p < 0.001, respectively). There was no significant difference in the incidence of postoperative acute kidney injury and B-type natriuretic peptide level between the two groups., Conclusion: The use of modified del Nido cardioplegia may reduce the incidence of abnormal mSID and hyperchloremia compared with the use of a chloride-rich cardioplegic solution., (© 2024. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

This review focuses on the development of therapeutic interventions for Alzheimer's dementia. While established treatments targeted acetylcholine and NMDA receptors, there is a growing demand for innovative therapies as the aging population increases. The paper highlights the US Food and Drug Administration's approval of aducanumab (Aduhelm) and lecanemab (Leqembi), emphasizing the developmental status of new treatments. Specifically, it covers seven principal drugs in Phase III trials, detailing their mechanisms of action, clinical trial specifics in the United States and Japan, and the current status of regulatory applications. The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease-modifying small molecules (fosgonimeton, hydralazine, masitinib). However, Gantenerumab and Solanezumab, unsuccessful in Phase III, are not covered. While the future approval status remains uncertain, we hope these drugs will offer beneficial therapeutic effects for potential dementia patients., (© 2024 The authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Forkhead box P3 (Foxp3)-expressing regulatory T (Treg) cells play essential roles in immune homeostasis but also contribute to establish a favorable environment for tumor growth by suppressing anti-tumor immune responses. It is thus necessary to specifically target tumor-infiltrating Treg cells to minimize effects on immune homeostasis in cancer immunotherapy. However, molecular features that distinguish tumor-infiltrating Treg cells from those in secondary lymphoid organs remain unknown. Here we characterize distinct features of tumor-infiltrating Treg cells by global analyses of the transcriptome and chromatin landscape. They exhibited activated phenotypes with enhanced Foxp3-dependent transcriptional regulation, yet being distinct from activated Treg cells in secondary lymphoid organs. Such differences may be attributed to the extensive clonal expansion of tumor-infiltrating Treg cells. Moreover, we found that TCF7 and LEF1 were specifically downregulated in tumor-infiltrating Treg cells both in mice and humans. These factors and Foxp3 co-occupied Treg suppressive function-related gene loci in secondary lymphoid organ Treg cells, whereas the absence of TCF7 and LEF1 accompanied altered gene expression and chromatin status at these gene loci in tumor-infiltrating Treg cells. Functionally, overexpression of TCF7 and LEF1 in Treg cells inhibited the enhancement of Treg suppressive function upon activation. Our results thus show the downregulation of TCF7 and LEF1 as markers of highly suppressive Treg cells in tumors and suggest that their absence controls the augmentation of Treg suppressive function in tumors. These molecules may be potential targets for novel cancer immunotherapy with minimum effects on immune homeostasis., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

[Purpose] Older patients with cardiovascular disease should increase their physical activity and prioritize positive psychological and social approaches in the maintenance phase of their cardiac rehabilitation. This study aimed to clarify the effect of small community walking on physical activity, well-being, and social capital in older patients with cardiovascular disease in the maintenance phase. [Participants and Methods] We conducted a multicenter study in Kumamoto, Japan. We randomly divided 55 patients with cardiovascular disease into two groups: small community walking and walking alone. For three months, a registered cardiac rehabilitation instructor provided walking guidance to both groups using a wearable device. We measured physical activity, social capital, and subjective happiness before and after the intervention. [Results] Results revealed a statistically significant main effect of time on physical activity and social participation. In the subjective happiness scale, there was an association between group and time. [Conclusion] Our results suggest that walking guidance using a wearable device was beneficial in improving overall physical activity, regardless of whether the individual did small community walking or walking alone. Furthermore, small community walking intervention may effectively enhance well-being. The relationship between physical activity and social participation needs to be further investigated., Competing Interests: The authors declare no conflict of interest., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Purpose: The aim of the present study was to translate the Singing Voice Handicap Index (SVHI) into Japanese and validate the Japanese version of the SVHI., Methods: The SVHI was translated into Japanese from the validated original version, and the questionnaire was administered to 102 singers with voice problems and 88 healthy singers. Internal consistency and test-retest methods were implemented to evaluate the reliability of this index. The internal consistency method assessed validity via Cronbach's α, and test-retest reliability was analyzed by the intraclass correlation coefficient (ICC) and limits of agreement (LoA) according to the Bland Altman method. Construct validity was verified by confirming correlations between SVHI scores and visual analog scale (VAS) scores for disability in singing using Spearman correlation. Discriminant validity was evaluated by comparing SVHI scores between singers with voice problems and healthy singers using t tests. Using the Tukey's honestly significant difference (HSD) test, we also compared the Voice Handicap Index (VHI) and SVHI scores among three groups: healthy singers, singers with voice problems solely during singing, and singers with voice problems during both speaking and singing., Results: The Japanese version of the SVHI showed excellent internal consistency (Cronbach's α = 0.981) and test-retest reliability (ICC: 0.93). The 95 percent LoA was calculated to be between -20.8 and 33.9. Construct validity was verified through correlated SVHI and VAS scores (r = 0.736, P < 0.001). Discriminant validity was verified as the SVHI scores of singers with voice problems were higher than those of healthy singers (77.8±37.5 vs. 30.0±26.5, P < 0.001). There were no statistically significant differences in VHI scores between singers with voice problems solely during singing and healthy singers; however, the SVHI scores of singers with voice problems solely during singing were significantly higher than those of healthy singers (63.4±36.8 vs. 30.0±26.5, P < 0.001)., Conclusion: We confirmed that the Japanese version of the SVHI is a valid and reliable self-rated questionnaire for measuring the patient-perceived impact of singing voice problems among Japanese singers., Competing Interests: Declarations of interest None., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

The aim of the present study was to develop a semi-quantitative urine pregnancy test for mares based on the Cuboni reaction and to verify the reliability of this test. The urine specimens were hydrolyzed by heating in the presence of hydrochloric acid. The resulting free estrogens were extracted from the urine matrix using toluene. Sulfuric acid was added to the toluene extract and the mixture was heated again. The lower layer in the test tube containing sulfuric acid was used for fluorescence measurements with excitation at 355 nm and measurement at 535 nm. The fluorometric Cuboni test revealed that the fluorescence counts in urine samples collected after the second trimester of gestation were significantly higher than those obtained from barren mares. The levels of estrogens, including equilin, estrone and estardiol-17β exhibited a dose-dependent increase in fluorescence counts, whereas other steroids, such as progesterone, testosterone, and cortisol, did not affect fluorescence. Heat treatment of urine samples with hydrochloric acid significantly increased the fluorescence counts in those collected after the second trimester of gestation compared to non-pregnant samples, implying the presence of large amounts of conjugated estrogens in pregnant mare urine. Fluorescence counts in urine samples obtained during pregnancy showed a positive relationship with estrone concentrations as measured by enzyme immunoassay. The results of the present study showed that the fluorometric Cuboni test facilitates urine fluorescence counts depending on the urinary estrogen content and is capable of discriminating between pregnancy and non-pregnancy states beyond the second trimester of gestation in mares.

Remimazolam is a new ultrashort-acting benzodiazepine sedative, the use of which has not been reported for pediatric cardiac surgery. This case report describes the use of remimazolam in a 6-year-old girl who underwent minimally invasive cardiac surgery with right-sided thoracotomy for an atrial septal defect. Under electroencephalographic monitoring, remimazolam (2-4 mg kg-1 h-1) and remifentanil (0.05 μg kg-1 min-1) were administered with an intercostal nerve block during the procedure. The patient awoke and was extubated promptly after surgery, without any serious adverse events, including intraoperative awareness. Remimazolam may be a viable option for general anesthesia during pediatric cardiac surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)