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Background:  Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) criteria were launched nearly 20 years ago. Following the revised conceptual definition of sepsis and subsequent omission of systemic inflammatory response syndrome (SIRS) score from the latest sepsis diagnostic criteria, we omitted the SIRS score and proposed a modified version of JAAM DIC criteria, the JAAM-2 DIC criteria., Objectives:  To validate and compare performance between new JAAM-2 DIC criteria and conventional JAAM DIC criteria for sepsis., Methods:  We used three datasets containing adult sepsis patients from a multicenter nationwide Japanese cohort study (J-septic DIC, FORECAST, and SPICE-ICU registries). JAAM-2 DIC criteria omitted the SIRS score and set the cutoff value at ≥3 points. Receiver operating characteristic (ROC) analyses were performed between the two DIC criteria to evaluate prognostic value. Associations between in-hospital mortality and anticoagulant therapy according to DIC status were analyzed using propensity score weighting to compare significance of the criteria in determining introduction of anticoagulants against sepsis., Results:  Final study cohorts of the datasets included 2,154, 1,065, and 608 sepsis patients, respectively. ROC analysis revealed that curves for both JAAM and JAAM-2 DIC criteria as predictors of in-hospital mortality were almost consistent. Survival curves for the anticoagulant and control groups in the propensity score-weighted prediction model diagnosed using the two criteria were also almost entirely consistent., Conclusion:  JAAM-2 DIC criteria were equivalent to JAAM DIC criteria regarding prognostic and diagnostic values for initiating anticoagulation. The newly proposed JAAM-2 DIC criteria could be potentially alternative criteria for sepsis management., Competing Interests: K.Y. reported receiving grants from Asahi Kasei Pharma and Japan Blood Products Organization. T.I. participated on advisory boards of Japan Blood Products Organization, Asahi Kasei Pharmaceuticals, and Toray Medical. None of the other authors have any potential conflicts of interest to disclose., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells abundant in human tissues that play a significant role in defense against bacterial and viral infections and in tissue repair. MAIT cells are activated by recognizing microbial-derived small-molecule ligands presented by the MHC class I related-1 protein. Although several MAIT cell modulators have been identified in the past decade, potent and chemically stable ligands remain limited. Herein, we carried out a structure-activity relationship study of ribityllumazine derivatives and found a chemically stable MAIT cell ligand with a pteridine core and a 2-oxopropyl group as the Lys-reactive group. The ligand showed high potency in a cocultivation assay using model cell lines of antigen-presenting cells and MAIT cells. The X-ray crystallographic analysis revealed the binding mode of the ligand to MR1 and the T cell receptor, indicating that it forms a covalent bond with MR1 via Schiff base formation. Furthermore, we found that the ligand stimulated proliferation of human MAIT cells in human peripheral blood mononuclear cells and showed an adjuvant effect in mice. Our developed ligand is one of the most potent among chemically stable MAIT cell ligands, contributing to accelerating therapeutic applications of MAIT cells.

Objective: Proximal ExTension to Induce COmplete ATtachment (PETTICOAT), which utilizes downstream bare metal stents for structural support, demonstrates potential, yet its adoption is limited by variable outcomes. This study elucidates the potential of PETTICOAT in aortic dissection, emphasizing the determinants that guide patient selection., Methods: A retrospective analysis of 60 patients who underwent full PETTICOAT for aortic dissections was conducted. A multivariate logistic regression model identified predictors of favorable aortic remodeling. Patients underwent standardized follow-up with CT scans to assess size, volumetric changes, and anatomical conditions. Selection criteria included full PETTICOAT application and a minimum three-month follow-up. Demographics, preoperative conditions, and procedural details were collected and analyzed., Results: The analysis identified predictors of favorable aortic remodeling, including age over 60, a larger downstream aorta stent graft, a smaller abdominal aorta (<450mm 2 ), and oral angiotensin II receptor blocker (ARB) administration. Over a median 47.5-month follow-up, survival rates in the favorable remodeling (97.3%) and unfavorable groups (100%) were similar. Downstream aortic event-free survival rates did not significantly differ (89.2% vs. 73.9%), although the unfavorable group had a relatively higher incidence of distal stent-induced new entries (26.1% vs. 8.1%)., Conclusions: The PETTICOAT concept effectively enhances aortic remodeling in complex aortic dissections. Predictors for favorable remodeling, including age, stent graft sizing, aortic diameter, and ARB therapy, offer insights for optimizing patient selection. This approach improves survival outcomes, mitigates risks associated with untreated aortic segments, and provides a minimally invasive solution for aortic dissections. Despite some outcome variations, the technique holds promise for addressing the challenges of aortic dissections, with the potential for further refinement in patient selection and technique application., Competing Interests: Declaration of interests The authors declare that they have no known competing interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The initial efficacy of placental extracts (Pla-Exts) and human mesenchymal stem-cell-derived exosomes (hMSC-Exo) against aging-induced stress in human dermal fibroblasts (HDFs) was examined. The effect of Pla-Ext alone, hMSC-Exo alone, the combined effect of Pla-Ext and hMSC-Exo, and the effect of hMSC-Exo (Pla/MSC-Exo) recovered from cultures with Pla-Ext added to hMSC were verified using collagen, elastin, and hyaluronic acid synthase mRNA levels for each effect. Cells were subjected to photoaging (UV radiation), glycation (glycation end-product stimulation), and oxidation (H 2 O 2 stimulation) as HDF stressors. Pla-Ext did not significantly affect normal skin fibroblasts with respect to intracellular parameters; however, a pro-proliferative effect was observed. Pla-Ext induced resistance to several stresses in skin fibroblasts (UV irradiation, glycation stimulation, H 2 O 2 stimulation) and inhibited reactive oxygen species accumulation following H 2 O 2 stimulation. Although the effects of hMSC-Exo alone or the combination of hMSC-Exo and Pla-Ext are unknown, pretreated hMSC-Exo stimulated with Pla-Ext showed changes that conferred resistance to aging stress. This suggests that Pla-Ext supplementation may cause some changes in the surface molecules or hMSC-Exo content (e.g., microRNA). In skin cells, the direct action of Pla-Ext and exosomes secreted from cultured hMSCs pretreated with Pla-Ext (Pla/MSC-Exo) also conferred resistance to early aging stress.

Left upper trisegmentectomy is expected to be as curative as lobectomy for lung cancer because the left upper lobe is anatomically the same as the combined upper and middle lobes of the right lung and the procedure can provide a sufficient surgical margin. In the present multicenter study, we compared the results of trisegmentectomy and lobectomy in patients with clinical stage T1c-2aN0M0 left upper lung cancer. We retrospectively analyzed the outcomes of patients with clinical stage T1c-2aN0M0 lung cancer in the left upper segment who underwent lobectomy or trisegmentectomy between January 2006 and June 2022. The trisegmentectomy group (S group) and lobectomy group (L group) comprised 33 and 132 patients, respectively. Comparisons of postoperative survival revealed no significant differences in overall survival (p = 0.761) or disease-free survival (p = 0.508) between the two groups. There were also no significant differences in survival after adjustment for clinical factors by Cox proportional hazards models and propensity score matching. Local recurrence was significantly more predominant in the S group than in the L group (p = 0.006). The S group had a worse postoperative survival than the L group when the tumor was located in anterior segment. Trisegmentectomy can provide an equivalent postoperative survive to lobectomy in patients with clinical stage T1c-2aN0M0 left upper segment lung cancer except in patients with tumor in anterior segment., (© 2024. Italian Society of Surgery (SIC).)

Barley is rich in β-glucan, which can alter gut microbiota and metabolome profiles, potentially affecting host metabolism. However, the microbiota and metabolites increased by barley β-glucan remain unclear. In this study, we focused on the gut-microbiota-derived metabolite succinate and investigated the microbiome and metabolome profiles altered by barley β-glucan intake. C57BL/6 J mice were fed a standard or middle-fat diet containing barley flour rich in β-glucan or barley flour without β-glucan, and their gut microbiota and metabolome profiles were analyzed. The results showed increased Bacteroides, Parasutterella, and succinate due to barley β-glucan intake independent of diet differences. Next, we used mice lacking slc13a2, a gene that is involved in the cellular uptake of succinate. Wild-type mice showed improved glucose tolerance after the intake of barley β-glucan, but this effect was attenuated in the slc13a2-deficient mice. These results suggest that barley β-glucan intake increases succinate and succinate-producing bacteria and affects glucose metabolism., (© 2024. The Author(s).)

Introduction: This study aimed to explore the association between ferroptosis, a newly identified type of cell death, and the role of retinoic acid in developing pregnancy complications. Therefore, the effects of all-trans retinoic acid (ATRA) on ferroptosis susceptibility in BeWo cells were assessed to understand abnormal placental development., Methods: BeWo cells were used as surrogates for cytotrophoblasts. The effect of ATRA on ferroptosis sensitivity was assessed on BeWo cells pretreated with ATRA or dimethyl sulfoxide (DMSO; control), following which the LDH-releasing assay was performed. The effects of ATRA pretreatment on the antioxidant defense system (including glutathione [GSH], mitochondrial membrane potential, and heme oxygenase-1 [HMOX1]) in BeWo cells were assessed using assay kits, RT-qPCR, and HMOX1 immunostaining. To evaluate the effect of ATRA on BeWo cells, HMOX1 was silenced in BeWo cells using shRNA., Results: ATRA pretreatment increased ferroptosis resistance in BeWo cells. Although with pretreatment, qPCR indicated upregulation of HMOX1, no significant change was observed in the GSH levels or mitochondrial membrane potential. This was corroborated by intensified immunostaining for heme oxygenase-1 protein (HO-1). Notably, the protective effect of ATRA against ferroptosis was negated when HO-1 was inhibited. Although HMOX1-silenced BeWo cells exhibited heightened ferroptosis sensitivity compared with controls, ATRA pretreatment counteracted ferroptosis in these cells., Discussion: ATRA pretreatment promotes BeWo cell viability by suppressing ferroptosis and upregulating HMOX1 and this can be used as a potential therapeutic strategy for addressing placental complications associated with ferroptosis., 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 article., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: We developed a method to measure the extracellular and intracellular fluid volumes using the kinetics of uric acid in the bodies of Japanese patients undergoing dialysis. In this research, we aimed to assess the prognosis of vascular events using this uric acid kinetic model method., Methods: We conducted a retrospective cohort study of 1,298 patients who were undergoing hemodialysis or predilution online hemodiafiltration at the end of December 2019 at 13 institutions in Japan. Information on vascular events was acquired in 2020. Vascular event prognosis was defined as the new incidence of one or more of the following four types of vascular events: myocardial infarction, cerebral infarction, cerebral hemorrhage, or limb amputation. We measured the extracellular fluid volume and intracellular fluid volume after dialysis using the uric acid kinetic model method and determined the association between ECV, ICV, and vascular event risk., Results: A high extracellular volume was substantially linked to an increased risk of vascular events. In addition, while a crude analysis revealed that a high intracellular volume was associated with a low risk of vascular events, this was not statistically significant after multifactorial adjustment. This result was partly affected by the low measurement accuracy of the serum urea nitrogen level used for the intracellular volume calculation., Conclusions: Extracellular volume calculated using the uric acid kinetic model method is a prognostic factor for vascular events in patients undergoing hemodialysis., (© 2023. The Japanese Society for Artificial Organs.)

Background: We examined the safety and efficacy of acceleration training (AT) in patients immediately after cardiac surgery., Methods and Results: This randomized controlled study included patients who underwent open-heart surgery using cardiopulmonary bypass. Of these patients, 31 received regular cardiac rehabilitation (CR) and 39 received AT in addition to regular CR (AT group). AT was provided using a vibration platform (Power Plate ® Pro7 TM and Power plate ® personal; Performance Health System, Chicago, IL, USA). The AT group performed 5 static resistance training sessions: squats, wide stance squats, toe stands, banded squats, and front lunges. Each vibration session lasted 30 s. We evaluated the short physical performance battery, anterior mid-thigh thickness, maximum voluntary isometric contraction of the knee extensors, and serum intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) concentrations as indicators of endothelial function. The observation period was during hospitalization and lasted approximately 20 days. No adverse events occurred during AT. Ultrasound revealed a significantly lower reduction in muscle mass at discharge in the AT group. No significant differences were observed in ICAM-1 and VCAM-1 concentrations between the 2 groups preoperatively, postoperatively, or at discharge., Conclusions: AT is considered safe and effective for patients immediately after open-heart surgery. AT, along with regular CR, may prevent skeletal muscle mass loss, muscle weakness, and physical function loss immediately after open-heart surgery.

Background: Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass., Methods and Results: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034)., Conclusions: Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Background: The prognosis for cancer patients has been improved because of the development of molecularly targeted drugs. Treatment of intracranial tumors must be personalized while prioritizing the treatment of comorbid cancers., Observations: A 38-year-old man presented with bloody sputum, bilateral multiple nodules, and a mass in the lower lobe of his right lung. Bronchoscopy revealed stage IV lung adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation. Screening head magnetic resonance imaging revealed a 38-mm-diameter mass in the left petroclival area. Because the patient was neurologically intact, the treatment of lung adenocarcinoma was prioritized, and the third-generation EGFR-tyrosine kinase inhibitor osimertinib was used. Although nodules in the lung began to shrink, the intracranial lesion expanded and caused hydrocephalus, necessitating a ventriculoperitoneal shunt. The tumor also caused diplopia, dysarthria, and gait abnormalities. A left anterior transpetrosal approach was used to remove the tumor derived from the trochlear nerve. The pathological examination revealed schwannoma. Neurological symptoms improved following surgery. Osimertinib was continued during the perioperative period., Lessons: Osimertinib was effective for lung adenocarcinoma but not for trochlear nerve schwannoma, which required surgical intervention. It is necessary to tailor the treatment of benign brain tumors in patients with concurrent malignant cancers. https://thejns.org/doi/10.3171/CASE24144.

Background: Perforated peptic ulcer (PPU) causes peritonitis and requires surgery based on disease severity. This study aimed to develop and validate a severity scale for PPU with generalized peritonitis., Materials and Methods: This retrospective cohort study used a nationwide multi-center surgical database (2013-2020). Patients aged >15 years who underwent surgery for PPU with generalized peritonitis were included and categorized into the derivation (2013-2018) and two validation (2019 and 2020) cohorts. Possible severity predictors were selected via a literature review, and Lasso models were developed to predict severe postoperative adverse events with 2000 bootstrapping. Final variables for the scoring system were determined based on inclusion frequency (≥90%) in the Lasso models. Discrimination and accuracy were evaluated using c-statistics and calibration plots. Cutoff values for minimal postoperative adverse events were examined using negative predictive values., Results: Among 12,513 patients included (1,202 underwent laparoscopic surgery), 533 (5.9%), 138 (7.6%), and 117 (6.9%) in the derivation and two validation cohorts experienced postoperative adverse events. Age, dyspnea at rest, preoperative sepsis, III/IV/V of American Society of Anesthesiologists physical status, and albumin and creatinine were selected for the final model. A 0-11 scoring system was developed with c-statistics of 0.812-0.819. Cutoff value was determined as 5, which predicted <3% probability of postoperative adverse events regardless of type of surgery., Conclusions: A score of <5 predicts minimal risks for postoperative adverse events and therefore would be clinically useful to determine type of surgery. Further studies are needed to validate the score., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Six percent of patients with Leigh syndrome (LS) present with infantile epileptic spasms syndrome (IESS). However, treatment strategies for IESS with LS remain unclear. This retrospective study aimed to evaluate the efficacy and safety of treatment strategies in patients with IESS complicated by LS and Leigh-like syndrome (LLS)., Methods: We distributed questionnaires to 750 facilities in Japan, and the clinical data of 21 patients from 15 hospitals were collected. The data comprised treatment strategies, including adrenocorticotropic hormone (ACTH) therapy, ketogenic diet (KD) therapy, and antiseizure medications (ASMs); effectiveness of each treatment; and the adverse events., Results: The median age at LS and LLS diagnosis was 7 months (range: 0 to 50), whereas that at the onset of epileptic spasms was 7 (range: 3 to 20). LS was diagnosed in 17 patients and LLS in four patients. Seven, two, five, and seven patients received ACTH + ASMs, ACTH + KD + ASMs, KD + ASMs, and ASMs only, respectively. Four (44%) of nine patients treated with ACTH and one (14%) of seven patients treated with KD achieved electroclinical remission within one month of treatment. No patients treated with only ASMs achieved electroclinical remission. Seven patients (33%) achieved electroclinical remission by the last follow-up. Adverse events were reported in four patients treated with ACTH, none treated with KD therapy, and eight treated with ASMs., Conclusion: ACTH therapy shows the best efficacy and rapid action in patients with IESS complicated by LS and LLS. The effectiveness of KD therapy and ASMs in this study was insufficient., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tohru Okanishi reports financial support was provided by Japan Society for the Promotion of Science. Hiroshi Matsumoto reports financial support was provided by Japan Society for the Promotion of 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 Inc. All rights reserved.)

Background: Older adults often face loneliness due to chronic illness or loss of close ones, a situation worsened by the COVID-19 pandemic. Increased loneliness heightens the risk of diseases, especially dementia, necessitating urgent action., Objective: This study aims to assess the impact of a virtual reality (VR)-based open-air bath program on depression and loneliness in older individuals with subjective cognitive decline/mild cognitive impairment attending the Dementia Medical Center in Kyoto, Japan. We further aim to evaluate the feasibility of the program (participant recruitment and adherence) and to measure program enjoyment and satisfaction., Methods: The study design is a crossover trial with a 1:1 ratio, wherein 12 participants will be randomly assigned to groups 1 and 2, with group 2 serving as a waitlist control and group 1 receiving the VR program from the onset for 6 months; the VR program will be conducted 6 times (monthly). Program completion for group 1 will be followed by an observation period from months 7 to 12. Group 2 will participate in the VR program from months 7 to 12, with an observation period from months 1 to 6. Cognitive tests, psychiatric assessments, and the University of California, Los Angeles Loneliness Scale will be conducted before the study, at 6 months, and at 12 months. Results will be analyzed using repeated-measures ANOVA. Head magnetic resonance imaging and single-photon emission computed tomography scans will be performed before and after the VR program to evaluate changes and effects on brain regions., Results: Recruitment began in September 2023 and data collection is expected to be completed by March 2025. Complete study results will be published by September 2025., Conclusions: This study examines the preliminary effects of VR on loneliness in older adults with predementia through open-air bath simulations. VR experiences could benefit this population, particularly those with limited outdoor activities. Quantifying VR's impact will aid in determining the size for a larger clinical trial. Qualitative results will inform participation mechanisms and guide the implementation and design of future trials., Trial Registration: University hospital Medical Information Network UMIN000052667; https://tinyurl.com/3yaccay5., International Registered Report Identifier (irrid): DERR1-10.2196/57101., (©Ayu Imai, Teruyuki Matsuoka, Chikara Nakayama, Nana Hashimoto, Mutsuo Sano, Jin Narumoto. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 01.08.2024.)

A male patient in his forties was diagnosed with primary aldosteronism following blood tests. The patient requested surgical treatment and was transferred to our department for adrenal vein sampling. Preoperative contrast-enhanced computed tomography (CT) revealed that the left adrenal vein (LAV) did not form a common trunk with the left inferior phrenic vein, and instead drained into both the left renal vein (LRV) and inferior vena cava (IVC) after the bifurcation. Angiography from the LAV showed a branch draining into the IVC. Left-sided sampling was performed. Aldosterone levels were elevated at all 3 sites. Because the sampling results were bilaterally positive, the patient was contraindicated for surgery. There are no reports of an anomalous LAV draining into both the LRV and IVC, making this case extremely unique. Regarding the LAV sampling site, it has been reported that aldosterone levels are higher in the common trunk than in the LAV. Therefore, we increased the number of blood sampling sites. In adrenal vein sampling, we often focus on the anatomy of the right adrenal vein because of difficulties in accessing to it. However, anomalies of the LAV may also occur. Therefore, it is important to determine the anatomy of both adrenal veins using preoperative contrast-enhanced CT to plan an appropriate sampling strategy., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background The question of whether antiplatelet therapy (APT) should be discontinued prior to gastrectomy is controversial. In this study, we investigated the impact of continuing aspirin preoperatively on perioperative bleeding and thromboembolic complications in patients receiving gastrectomy for malignancy. Methods The study cohort comprised 1001 patients with malignant gastric tumors who had undergone gastrectomy between 2005 and 2021. This study excludes emergency surgery. The patients were allocated to the following three groups: those who continued aspirin monotherapy prior to surgery (cAPT group), those who stopped receiving it seven days prior to surgery (dAPT group), and those who did not take APT at any stage (non-APT group). The differences between the groups in intraoperative and postoperative complications, such as bleeding and thromboembolism, were examined. Results The non-APT group comprised 682 patients, the dAPT group had 164, and the cAPT group had 155. There were 22 bleeding events (2.2%) in the whole cohort, 11 (1.1%) of which occurred in the non-APT group, six (3.7%) in the dAPT group, and five (3.2%) in the cAPT group. The differences between the three groups were not significant in terms of bleeding complications. There were 10 (1.0%) thromboembolic events in the whole cohort, five (0.7%) of which occurred in the non-APT group, four (2.4%) in the dAPT group, and one (0.6%) in the cAPT group. The differences between the three groups were not significant in terms of thromboembolic complications. In a multivariate analysis of the whole cohort, intraoperative blood loss (≥1000 mL) (p < 0.001, odds ratio (OR) = 11.8) and multidrug APT (p < 0.001, OR = 7.8) were both independent predictors of bleeding complications. However, continuing to take aspirin before surgery was not a risk factor for bleeding complications. Conclusions In patients with malignant gastric tumors, preoperative continuation of aspirin monotherapy has no impact on either intraoperative or postoperative bleeding. Gastrectomy can be performed safely, even in patients who continue aspirin treatment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Kokura Memorial Hospital’s Institutional Review Board issued approval 19061903. 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, Matsuoka et al.)

Syntaxin-binding protein 1 (STXBP1) is a presynaptic protein that plays important roles in synaptic vesicle docking and fusion. STXBP1 haploinsufficiency causes STXBP1 encephalopathy (STXBP1-E), which encompasses neurological disturbances including epilepsy, neurodevelopmental disorders, and movement disorders. Most patients with STXBP1-E present with regression and movement disorders in adulthood, highlighting the importance of a deeper understanding of the neurodegenerative aspects of STXBP1-E. An in vitro study proposed an interesting new role of STXBP1 as a molecular chaperone for α-Synuclein (αSyn), a key molecule in the pathogenesis of neurodegenerative disorders. However, no studies have shown αSyn pathology in model organisms or patients with STXBP1-E. In this study, we used Drosophila models to examine the effects of STXBP1 haploinsufficiency on αSyn-induced neurotoxicity in vivo. We demonstrated that haploinsufficiency of Ras opposite (Rop), the Drosophila ortholog of STXBP1, exacerbates compound eye degeneration, locomotor dysfunction, and dopaminergic neurodegeneration in αSyn-expressing flies. This phenotypic aggravation was associated with a significant increase in detergent-insoluble αSyn levels in the head. Furthermore, we tested whether trehalose, which has neuroprotective effects in various models of neurodegenerative disorders, mitigates αSyn-induced neurotoxicity exacerbated by Rop haploinsufficiency. In flies expressing αSyn and carrying a heterozygous Rop null variant, trehalose supplementation effectively alleviates neuronal phenotypes, accompanied by a decrease in detergent-insoluble αSyn in the head. In conclusion, this study revealed that Rop haploinsufficiency exacerbates αSyn-induced neurotoxicity by altering the αSyn aggregation propensity. This study not only contributes to understanding the mechanisms of neurodegeneration in STXBP1-E patients, but also provides new insights into the pathogenesis of α-synucleinopathies., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Mismatch negativity (MMN) is automatically elicited by incoming sound deviation compared to the neural representation of preceding homogenous sounds stored in the brain's auditory sensory memory. This study aimed to assess time-functional deviation sensitivity in auditory sensory memory associated with a temporal window of integration (TWI) of 160-170 msec in patients with schizophrenia. To this end, we measured the magnetic counterpart of the MMN (MMNm) in 20 patients with schizophrenia on medication and 20 healthy age-matched adults as a control group responding to an omitted tone segment incorporated into a complex sound of 176 ms duration corresponding to the TWI duration. Overall, the magnitude of the MMNm was smaller in the patients with schizophrenia than in the healthy control group. The peak latency of the MMNm was prolonged in the latter omitted segments for both groups, but to a greater extent in patients with schizophrenia. These results indicate that deviation detection is impaired in the later part of the TWI, corresponding to the duration of auditory sensory memory in patients with schizophrenia. Thus, the specific impairment of MMN in response to duration deviants (duration MMN), as previously reported, might result from a damaged mechanism in the later part of the TWI of sensory memory, suggesting that a decline in sensory memory causes distorted perception or disturbances in cognitive function in patients with schizophrenia., 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.

Objective: Loneliness reportedly increases the risk of dementia, especially Alzheimer's disease (AD). The authors' previous study demonstrated associations between loneliness and structural abnormalities observed in early-stage AD. The present study examined associations between the brain's functional characteristics and loneliness among older adults with concerns about cognitive decline., Methods: This single-center study included 43 participants (13 with amnestic mild cognitive impairment and 30 with normal cognition). Participants were assessed with the revised University of California Los Angeles (UCLA) Loneliness Scale and underwent resting-state functional MRI. Functional images were preprocessed with the CONN toolbox. The selected seeds were within brain regions reportedly associated with loneliness. One-sample general linear model analysis was performed to examine regressions of UCLA Loneliness Scale scores and functional connectivity between the seeds and regions of interest., Results: The revised UCLA Loneliness Scale scores were positively correlated with functional connectivity between the right hippocampus and left lateral parietal lobe and were negatively correlated with functional connectivity between the left amygdala and left frontal operculum and between the left amygdala and right supramarginal gyrus. Analyses were adjusted for age, sex, and education and scores on the Mini-Mental State Examination and Clinical Dementia Rating scale., Conclusions: Loneliness was associated with abnormal function of the hippocampus, parts of the parietal lobe and frontal cortex, and the amygdala. These findings may suggest a possible correlation between loneliness and neurological changes associated with dementia., Competing Interests: Dr. Matsuoka has received speaker’s fees from Eisai, Merck Sharp and Dohme, Otsuka, Sumitomo Pharma, and Takeda and grant support from AbbVie, Boehringer Ingelheim, and Otsuka. The other authors report no financial relationships with commercial interests.

Aims: Identifying patients with vulnerable plaque who have poor prognosis among those with coronary artery disease (CAD) is crucial to deciding future therapeutic interventions. We previously reported that male CAD patients with low anti-apolipoprotein B-100 autoantibody (anti-apoB-100 Ab) levels were at an increased risk of developing unstable plaque lesions. This study focused on the autoantibodies against lipoprotein lipase (LPL), a key enzyme in triglyceride metabolism, which is another risk factor for atherosclerosis, and investigated their association with plaque characteristics., Methods: We measured serum anti-LPL Ab levels using a homemade enzyme-linked immunosorbent assay in 80 male CAD patients. Coronary plaque properties were evaluated using iMAP ® -intravascular ultrasound., Results: Serum anti-LPL Ab levels were not correlated with plaque burden but were significantly negatively and positively correlated with fibrotic and necrotic plaques, respectively. High-risk patients with low anti-apoB-100 Ab levels were divided into groups according to their anti-LPL Ab levels. The group with high anti-LPL Ab levels exhibited more necrotic plaques and fewer fibrotic plaques as well as higher remnant-like lipoprotein particle levels than the group with low anti-LPL Ab levels., Conclusions: Serum anti-LPL Ab levels can serve as a marker of plaque instability in CAD patients and can help identify higher-risk cases when combined with anti-apoB-100 Ab levels.

Background: The clinical development program of the SQ grass, ragweed, tree, and house dust mite (HDM) sublingual immunotherapy (SLIT)-tablets for allergic rhinitis/conjunctivitis (AR/C) included clinical trials conducted in North America, Europe, and Japan. Objective: Data from these trials were analyzed to assess efficacy, immunologic mechanisms, and safety outcomes across allergens and geographic regions. Methods: Thirteen phase III, double-blind, placebo controlled trials in the subjects with AR/C were conducted in North America, Europe (including Russia), and Japan (N = 7763 analyzed). Trials were generally similar with respect to medical practice, target population, eligibility criteria, and efficacy and safety monitoring. Data were analyzed for the approved doses in North America and Europe. Four statistical models were used to enhance comparison of the efficacy end points among the trials. Results: The SLIT-tablets demonstrated consistent efficacy across allergens and regions, regardless of the statistical analysis used. Relative improvement in the primary efficacy end point compared with placebo by using the predefined protocol analysis ranged from 17.9% to 32.8%, 17.5% to 19.3%, 20.6% to 38.3%, and 39.6% with the grass, HDM, ragweed, and tree SLIT-tablets, respectively. The kinetics of specific immunoglobulin E (IgE) and IgG4 responses were similar among the allergens and regions. Local application-site reactions were the most common adverse events for all allergens and in all regions. Most treatment-related adverse events for all allergens and in all regions were mild in severity. The rate of systemic allergic reactions was similar across regions (0%-0.54%). Conclusion: Confirmatory phase III trials for SLIT-tablets in the treatment of AR/C showed consistent efficacy, immunologic, and safety outcomes across allergens and geographic regions.

Introduction: This study aimed to investigate the mechanism of memory function in the context of explicit memory in early-stage Alzheimer's disease (AD) using the short-form Japanese Verbal Learning Test (JVLT-9)., Methods: Participants were 20 patients with early-stage AD and a control group of 23 healthy older adults (normal controls: NC), each of whom was administered the JVLT-9, which is a verbal list learning task used to assess explicit memory comprehensively. Between-group differences for each score were investigated using the Mann-Whitney U test. A two-way analysis of variance (ANOVA) was performed for the number of correct recalls by group (AD/NC) × JVLT-9 task. In addition, the AD group was divided into a CDR 0.5 group and a CDR 1.0 group, and it was performed as a group (CDR 0.5/1.0) × JVLT-9 task two-way ANOVA., Results: The results demonstrated that the AD group had lower immediate recall, learning rate, semantic clustering, and recognition discrimination and significantly higher intrusion errors compared to the NC group. Further, JVLT-9 recall and recognition rates were found to be lower with higher CDR (an index of dementia severity)., Conclusion: These results are largely consistent with the features of explicit memory in AD reported in the English version, confirming the clinical utility of the JVLT-9 as a test of explicit memory function., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Review Committee, University of Toyama issued approval 27-10. The Toyama University Ethics Review Committee for Clinical and Epidemiological Research issued approval (approval number 27-10 dated 05/12/2015). 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, Matsui et al.)

Background: As the COVID-19 epidemic continues, concerns about long-term health impacts, specifically long COVID, persist. While the prevalence and symptomatology of long COVID have been explored in various global contexts, large-scale cohort studies in Japan remain limited, especially after the advent of the Omicron variant., Methods: In this observational study, 4,047 residents with a history of COVID-19 living in Toyonaka City, Osaka Prefecture, were assessed for long COVID symptoms using the VOICE mobile application and a paper survey. Respondents provided demographic and health information, as well as information regarding COVID-19 infection and subsequent symptoms. A Cox proportional hazard regression model was used to estimate the multivariable-adjusted hazard ratios and 95 % confidence intervals for overall morbidity of long COVID symptoms., Results: The survey found that 5.2 % of participants reported the persistence of one or more symptoms at 30 days post-onset. Fatigue was the most commonly reported symptom (1.75 %), followed by hair loss (1.41 %), and cough (1.28 %). Factors associated with an increased risk of experiencing long COVID symptoms included BMI, severe illness during the acute phase, and infection with certain COVID-19 variant strains, including Alpha, Delta, and Omicron. However, the incidence rate of long COVID appears to be decreasing with the dominance of the Omicron variant., Conclusions: This large-scale study from Toyonaka City suggests a 5.2 % prevalence rate for persistent COVID-19 symptoms 4 weeks post-infection, potentially indicating a lower prevalence of long COVID in Japanese populations after the rise of the Omicron variant., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Limited research has evaluated the long-term outcomes of prospective audit and feedback (PAF) led by pharmacists. We assessed pharmacist-led PAF processes and outcome measures over 8 years., Methods: This study was conducted at a single public hospital in Japan. Between 2014 and 2021, pharmacists conducted weekday PAFs for hospitalized patients and annually evaluated the process and outcome measures. The endpoints included detection of drug-resistant bacteria, drug susceptibility rates, duration of antimicrobial therapy, and proportion of long-term administration., Results: Among inpatients, methicillin-resistant Staphylococcus aureus significantly decreased from 50.9% in 2014 to 32.8% in 2021 (P < .001). The susceptibility rate of Pseudomonas aeruginosa to meropenem significantly increased from 91.2% in 2014 to 94.4% in 2021 (P < .001) and levofloxacin increased from 84.9% in 2014 to 89.3% in 2021 (P < .001). Antimicrobial therapy duration did not differ significantly between 2014 and 2016, but decreased significantly from 2017 onwards (P < .001), except in 2018. The number of patients receiving intravenous antimicrobials for >10 days decreased significantly between 2014 and 2021 (P < .001)., Conclusions: Long-term continuous PAF interventions by pharmacists contribute to improving and maintaining process and outcome indicators and prevent the spread of drug-resistant bacteria., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: In many countries, emergency medical systems were responsible for initial treatment of patients with COVID-19. Generally, acceptance by medical institutions may not be sufficient, and it may take much time to determine the medical institution to which to transport the patient. This problem is termed "difficulty in hospital acceptance (DIH)," and it is used as a key performance indicator in the assessment of the EMS in Japan. The purpose of this study was to reveal the factors associated with the DIH during the COVID-19 pandemic using dataset in the ORION (Osaka emergency information Research Intelligent Operation Network system)., Methods: This was a retrospective descriptive study with a 3-year study period from January 1, 2019 to December 31, 2021. We included patients who were recorded in the ORION system during the study period. The primary endpoint was defined as DIH. Multivariable logistic regression model was used to assess factors associated with DIH during the COVID-19 pandemic and calculated their adjusted odds ratio (AOR) and associated 95% confidence interval (CI)., Results: 1,078,850 patients included in this study. Of them, 41,140 patients (3.8%) experienced DIH and 1,037,710 patients (96.2%) did not experience DIH. The median age was 71 years (IQR: 45-82), and 543,760 patients (50.4%) were male. In this study, SpO 2 , body temperature, and epidemic period of COVID-19 were associated with difficulty in hospital acceptance. The highest AOR of SpO2 was 80% or less (AOR: 1.636, [95% CI: 1.532-1.748]), followed by 81-85% (AOR: 1.584, [95% CI: 1.459-1.721]). The highest AOR of body temperature was 38.0-38.9°C (AOR: 1.969 [95% CI: 1.897-2.043]), followed by 39°C or higher (AOR: 1.912 [95% CI: 1.829-1.998]). The highest AOR of epidemic period of COVID-19 was the 4th wave (AOR: 2.134, [95% CI: 2.065-2.205]), followed by the 3rd wave (AOR: 1.842, [95% CI: 1.785-1.901])., Conclusion: In this study, we revealed factors associated with the DIH during the COVID-19 pandemic. As various factors are involved in the spread of an unknown infectious disease, it is necessary not only to plan in advance but also to take appropriate measures according to the situation in order to smoothly accept emergency patients., 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 Katayama, Tanaka, Nakao, Tachino, Hirose, Dohmi, Kitamura, Oda and Matsuoka.)

Introduction: ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not., Research Design and Methods: Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year., Results: The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR., Conclusions: Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD., Trial Registration Number: UMIN000011525., Competing Interests: Competing interests: JW receives speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kyowa Kirin, Novo Nordisk, and Mitsubishi Tanabe, and receives grant support from Bayer, Chugai, Kyowa Kirin, Otsuka, Shionogi, Sumitomo, and Mitsubishi Tanabe., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Gastric cancer (GC) is one of the most common cancers worldwide. Most patients are diagnosed at the progressive stage of the disease, and current anticancer drug advancements are still lacking. Therefore, it is crucial to find relevant biomarkers with the accurate prediction of prognoses and good predictive accuracy to select appropriate patients with GC. Recent advances in molecular profiling technologies, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, have enabled the approach of GC biology at multiple levels of omics interaction networks. Systemic biological analyses, such as computational inference of "big data" and advanced bioinformatic approaches, are emerging to identify the key molecular biomarkers of GC, which would benefit targeted therapies. This review summarizes the current status of how bioinformatics analysis contributes to biomarker discovery for prognosis and prediction of therapeutic efficacy in GC based on a search of the medical literature. We highlight emerging individual multi-omics datasets, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics, for validating putative markers. Finally, we discuss the current challenges and future perspectives to integrate multi-omics analysis for improving biomarker implementation. The practical integration of bioinformatics analysis and multi-omics datasets under complementary computational analysis is having a great impact on the search for predictive and prognostic biomarkers and may lead to an important revolution in treatment.

Fatigue can lead to several health issues and is particularly prevalent among elderly individuals with chronic inflammatory conditions. Ninjin'yoeito, a traditional Japanese herbal medicine, is used to address fatigue and malaise, anorexia, and anemia. This study aimed to examine whether relieving inflammation in the brain and skeletal muscle of senescence-accelerated mice prone 8 (SAMP8) could reduce fatigue-like conditions associated with aging. First, SAMP8 mice were divided into two groups, with and without ninjin'yoeito treatment. The ninjin'yoeito-treated group received a diet containing 3% ninjin'yoeito for a period of 4 months starting at 3 months of age. At 7 months of age, all mice underwent motor function, treadmill fatigue, and behavioral tests. They were then euthanized and the skeletal muscle weight, muscle cross-sectional area, and concentration of interleukin (IL)-1β and IL-1 receptor antagonist (IL-1RA) in both the brain and skeletal muscle were measured. The results showed that the ninjin'yoeito-treated group had higher motor function and spontaneous locomotor activity than the untreated group did and ran for significantly longer in the treadmill fatigue test. Moreover, larger muscle cross-sectional area, lower IL-1β concentrations, and higher IL-1RA concentrations were observed in both the brain and skeletal muscle tissues of the ninjin'yoeito-treated group than in the untreated group. The results suggest that ninjin'yoeito improves age-related inflammatory conditions in both the central and peripheral tissues and reduces fatigue., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KM and YM are company employees of the funding partner, Tsumura & Co. However, they have only funded the study and have no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright: © 2024 Otsuka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background Although various types of adhesion barriers are widely utilized in liver surgery, the safety and feasibility of their use during repeat robotic liver resection (R-RLR) are still unknown. Methods Among the 68 patients undergoing RLR with the application of the spray-type adhesion barrier at Kokura Memorial Hospital, Kitakyushu, Japan, between 2021 and 2023, 24 cases that underwent R-RLR were included in this study. The included patients were divided into two groups: those who underwent previous hepatectomy with the use of a spray-type adhesion barrier (R-RLR-B, n = 14) and those without its previous use (R-RLR-NB, n = 10). The perioperative outcomes were compared between the groups. Results There were no differences between the R-RLR-B and R-RLR-NB groups in background characteristics, difficulty scores, operative and console time, or surgical blood loss. Although no difference was found between the groups in the time required for adhesiolysis before the robotic operation, both the time required for robotic adhesiolysis (75 minutes vs. 58 minutes, p = 0.034) and total time for adhesiolysis (192 minutes vs. 141 minutes, p = 0.014) were significantly shorter in the R-RLR-B group than in the R-RLR-NB group. Otherwise, there was no conversion to open hepatectomy, no intraoperative transfusion of red blood cells, no cases of grade B or C post-hepatectomy liver failure, and no mortality in the whole cohort. Conclusions The spray-type adhesion barrier may not be associated with an increase in the incidence of postoperative complications, including bile leakage or intraperitoneal abscess. In addition, its application during the previous hepatectomy can facilitate a secure R-RLR with reduced time for adhesiolysis. Thus, the use of the spray-type adhesion barrier for R-RLR is safe, effective, and time efficient., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Fujikawa et al.)

Background:  Septic-associated disseminated intravascular coagulation (DIC) is heterogeneous regarding prognosis and responsiveness to anticoagulant therapy., Objectives:  To investigate the relationship between the timing of development and recovery of DIC, its prognosis, and the difference in response to anticoagulant therapy in sepsis-associated DIC patients., Methods:  This study was performed with a dataset from a multicenter nationwide retrospective cohort study (J-Septic DIC registry) in Japan between 2011 and 2013 to reveal the subgroup "high risk of death in DIC" and investigate the relationship between anticoagulant use and mortality. Patients were assigned to four groups based on the International Society on Thrombosis and Haemostasis-overt DIC status at days 1 and 3: non-DIC (-/-), early-recovered DIC (+/-), late-onset DIC (-/+), and persistent DIC (+/+)., Results:  A total of 1,922 patients were included. In-hospital mortality in persistent and late-onset DIC patients was significantly higher than in patients with non-DIC and early-recovered DIC. This finding indicates that persistent DIC and late-onset DIC were a poor-prognosis subgroup, "high-risk" DIC. Meanwhile, patients with high-risk DIC treated with anticoagulants had significantly better outcomes than those without anticoagulants after adjusting for confounding factors., Conclusion:  This study showed that individuals with a high risk of death, persistent DIC, and late-onset DIC were a poor-prognostic subgroup in septic DIC; however, high-risk DIC is also a subgroup that can obtain more benefits from anticoagulant therapy., Competing Interests: K.Y. has received research grants from Asahi Kasei Pharma and Japan Blood Products Organization. T.I has received a research grant from JIMRO and has participated in advisory boards of Japan Blood Products Organization and Toray Medical., (Thieme. All rights reserved.)

Metal-nanoparticle (NP)/metal-organic framework (MOF) composites have attracted considerable attention as heterogeneous catalysts. Compared with porous carbon, silica, and alumina, the charge-transfer interaction between the metal NPs and the MOF accelerated the catalytic activity. In this study, PdRu bimetallic NPs were successfully immobilized on MOFs such as MIL-101(Cr) by using supercritical carbon dioxide. The STEM-EDX images show a uniform 3D distribution of the PdRu bimetallic NPs on MIL-101(Cr). The resulting PdRu@MIL-101(Cr) catalyst exhibited higher CO oxidation than monometal/MOF composites such as Pd@MIL-101(Cr) and Ru@MIL-101(Cr). Furthermore, PdRu@MIL-101(Cr) exhibited higher catalytic activity than PdRu@SiO 2 . This is because the particle size of the PdRu bimetallic NPs in MIL-101(Cr) was within the range of 2-3 nm. The synergistic effects were based on the combination of two metals, Pd and Ru, small bimetal particle formation, and charge-transfer interactions between the bimetal NPs and the MOF. These factors enhance the catalytic activity of the bimetal/MOF composites., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The cause of intracranial calcification is not fully understood. The aim of the current study was to identify factors associated with intracranial calcification and to determine whether these factors differ in calcification of different sites. A total of 404 community-dwelling people aged 65 or older were included in the study. All subjects underwent brain computed tomography (CT), blood tests, and a Mini-Mental State Examination (MMSE). Intracranial calcifications were scored using CT. Stepwise regression analysis was performed to examine factors associated with intracranial calcification, with each calcification score used as a dependent variable. Independent variables included age, gender, hemoglobin A1c (HbA1c), dyslipidemia, estimated glomerular filtration rate (eGFR), blood pressure, body mass index (BMI), smoking, serum iron, ferritin, and intact parathyroid hormone (PTH). Stepwise regression analysis detected male gender as a predictor of pineal gland calcification and intact PTH as a predictor of basal ganglia calcification. Age and lifestyle diseases were identified as predictors of calcification of the falx cerebri, internal carotid arteries, and vertebral arteries. These results indicate that the mechanisms of calcifications of the pineal gland and basal ganglia might differ from that of artery calcification, and that causes of intracranial calcification might be classified using factors that are and are not related to atherosclerosis., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Satoaki Matoba reports financial support was provided by JST 10.13039/501100009033COI. 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., (© 2024 The Authors.)

Aims: There have been inconsistent reports regarding the effect of antithrombin on sepsis; furthermore, there are limited reports on how dosage affects therapeutic efficacy. Thus, we aimed to perform a systematic review and meta-analysis of the use of antithrombin for sepsis and a meta-regression analysis of antithrombin dosage., Methods: We included randomized controlled trials (RCTs) and observational studies of adult patients with sepsis who received antithrombin. Outcomes included all-cause mortality and serious bleeding complications. Statistical analyses and data synthesis were performed using a random-effects model; further, meta-regression and funnel plots were used to explore heterogeneity and biases., Results: Seven RCTs and six observational studies were included. Most patients in the RCTs and observational studies had severe sepsis and septic-disseminated intravascular coagulation (DIC), respectively. A meta-analysis using RCTs showed no significant differences in mortality between the antithrombin and control groups. However, the meta-analysis of observational studies indicated a trend of decreasing mortality rates with antithrombin administration (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.68-0.92; p  = 0.002). Bleeding complications were significantly higher in the antithrombin group than in the control group in both study types (OR, 1.90; 95% CI, 1.52-2.37; p  < 0.01). The meta-regression analysis showed no correlation between antithrombin dosage and mortality., Conclusion: A meta-analysis of RCTs confirmed no survival benefit of antithrombin, whereas that of observational studies, which mostly focused on septic DIC, showed a significant beneficial effect on improving outcomes. Indications of antithrombin should be considered based on its beneficial and harmful effects., Competing Interests: T.W. received honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Asahi Kasei Pharma and Japan Blood Products Organization. K.Y. reported receiving a research grant from Japan Blood Products Organization. T.I received a grant from JIMRO, a consulting fee from Japan Blood Products Organization, and honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Asahi Kasei Pharma and Toray Medical. The other authors declare no conflict of interests for this article. T.I. is an Editorial Board member of AMS Journal and a co‐author of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication., (© 2024 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Introduction: This article investigates the evolving landscape of diplomacy in the digital age, focusing on diplomats at the United Nations (UN) Headquarters in New York. The central inquiry revolves around how diplomatic actors use digital tools to complement or augment traditional face-to-face diplomacy., Methods: We systematically compare a substantial corpus of X posts (tweets) from UN diplomats with their public statements at the United Nations Security Council (UNSC), employing advanced computational social science techniques. This study applies a range of large-scale text analysis methods, including word embedding, topic modeling, and sentiment analysis, to investigate systematic differences between offline and online communication., Results: Our analysis reveals that, while the essence of diplomacy remains consistent across both domains, there is strategic selectivity in the use of online platforms by diplomats. Online communication emphasizes non-security topics, ceremonial matters, and prominent policy stances, in contrast to the operational issues common in UNSC deliberations. Additionally, online discourse adopts a less confrontational, more public diplomacy-oriented tone, with variations among countries., Discussion: This study offers one of the first systematic comparisons between offline and online diplomatic messages. It illuminates how diplomats navigate the digital realm to complement traditional roles. The findings indicate that some elements of public diplomacy and nation branding, directed toward a wider audience far beyond the council chamber, have become an integral part of multilateral diplomacy unfolding at the UNSC., 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 Sakamoto, Araki, Ito and Matsuoka.)

The importance of temporary mechanical circulatory support for treating acute heart failure with cardiogenic shock is increasingly recognized, and Impella (Abiomed, Danvers, MA, USA) has received particular attention in this regard. Impella is an axial flow left ventricular assist device (LVAD) built into the tip of a catheter. It is inserted via a peripheral artery and implanted into the left ventricle. Although the morphology of Impella is different from a typical LVAD, it has similar actions and effects as an LVAD in terms of left ventricular drainage and aortic blood delivery. Impella increases mean arterial pressure (MAP) and systemic blood flow, thereby improving peripheral organ perfusion and promoting recovery from multiple organ failure. In addition, left ventricular unloading with increased MAP increases coronary perfusion and decreases myocardial oxygen demand, thereby promoting myocardial recovery. Impella is also useful as a mechanical vent of the left ventricle in patients supported with veno-arterial extracorporeal membrane oxygenation. Indications for Impella include emergency use for cardiogenic shock and non-emergent use during high-risk percutaneous coronary intervention and ventricular tachycardia ablation. Its intended uses for cardiogenic shock include bridge to recovery, durable device, heart transplantation, and heart surgery. Prophylactic use of Impella in high-risk patients undergoing open heart surgery to prevent postcardiotomy cardiogenic shock is also gaining attention. While there have been many case reports and retrospective studies on the benefits of Impella, there is little evidence based on sufficiently large randomized controlled trials (RCTs). Currently, several RCTs are now ongoing, which are critical to determine when, for whom, and how these devices should be used. In this review, we summarize the principles, physiology, indications, and complications of the Impella support and discuss current issues and future expectations for the device., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction While there are several advantages to utilizing robotics in liver surgery compared to traditional open and laparoscopic approaches, the most challenging part of robotic liver resection (RLR) remains the liver parenchymal transection. This is primarily due to the constraints of the existing robotic tools and the absence of a standard procedure. This study presents detailed technical aspects of our novel saline-linked cautery (SLiC) method for RLR and assesses the short-term outcomes for both non-anatomical and anatomical RLRs. Methods In this study, 82 cases that underwent RLR utilizing the SLiC method at our hospital from September 2021 to December 2023 were examined. A novel SLiC method is introduced in this study for robotically transecting the liver parenchyma utilizing bipolar cautery or monopolar scissors. The technique involves activating the SLiC and robotic suctioning simultaneously. The included patients were divided into two groups: patients undergoing robotic anatomical hepatectomy (n=39), and those receiving robotic non-anatomical hepatectomy (n=43). Short-term outcomes, including intraoperative and postoperative complications, were assessed in patients receiving both anatomical and non-anatomical hepatectomies. Results In the whole cohort, 74% of patients had performance status 1 or 2, and 24% were classified as Child-Pugh class B. RLR was performed without Pringle's maneuver in more than 80% of cases in patients receiving robotic non-anatomical hepatectomy, and more than 80% of patients undergoing robotic anatomical hepatectomy required only four or fewer 15-minute Pringle's maneuvers. There was no conversion to open hepatectomy, no cases of grade B or C post-hepatectomy liver failure, and no mortality in the entire cohort. Four postoperative complications with CDC IIIa or higher occurred (small bowel obstruction in two cases, intraabdominal hemorrhage in one, and bile leak in another), but no differences in the frequency of complications were found between those undergoing non-anatomical and anatomical hepatectomy (p=0.342). Conclusions The SLiC method, which involves simultaneously activating SLiC and robotic suctioning with either monopolar scissors or bipolar cautery, appears to be a secure and convenient technique for liver parenchymal transection in RLR. This innovative method permits precise access to the major Glissonean and venous structures within the liver, making RLR more standardized and easily applicable in routine patient care., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Fujikawa et al.)

Chronic kidney disease (CKD) affects around 850 million people worldwide, posing significant challenges in healthcare due to complications like renal anemia, end-stage kidney disease, and cardiovascular diseases. This review focuses on the intricate interplay between iron metabolism, inflammation, and renal dysfunction in CKD. Renal anemia, prevalent in CKD, arises primarily from diminished erythropoietin (EPO) production and iron dysregulation, which worsens with disease progression. Functional and absolute iron deficiencies due to impaired absorption and chronic inflammation are key factors exacerbating erythropoiesis. A notable aspect of CKD is the accumulation of uremic toxins, such as indoxyl sulfate (IS), which hinder iron metabolism and worsen anemia. These toxins directly affect renal EPO synthesis and contribute to renal hypoxia, thus playing a critical role in the pathophysiology of renal anemia. Inflammatory cytokines, especially TNF-α and IL-6, further exacerbate CKD progression and disrupt iron homeostasis, thereby influencing anemia severity. Treatment approaches have evolved to address both iron and EPO deficiencies, with emerging therapies targeting hepcidin and employing hypoxia-inducible factor (HIF) stabilizers showing potential. This review underscores the importance of integrated treatment strategies in CKD, focusing on the complex relationship between iron metabolism, inflammation, and renal dysfunction to improve patient outcomes.

Objective In 2022, Wenning et al. proposed the Movement Disorder Society Criteria (MDS Criteria) for the Diagnosis of Multiple System Atrophy (MSA). These criteria were expected to provide useful alternatives to the second consensus statement. We examined trends in these diagnostic criteria. Methods We used patient data registered with the Hokkaido Rare Disease Consortium for Multiple System Atrophy, which has been recruiting patients with MSA through medical facilities in Hokkaido since November 2014. Patients were evaluated according to the MDS criteria based on neurological examinations and imaging findings at three separate times: the first evaluation, the time of enrollment (diagnosis), and the most recent evaluation (final evaluation). Results The MDS criteria were examined in 68 of 244 patients enrolled between November 2014 and July 2022. At the initial evaluation, the classifications were as follows: clinically established (n=27; 39.7%); clinically probable (n=13; 19.1%); possible prodromal (n=12; 17.6%); and negative (did not meet criteria (n=16; 23.5%). At the time of diagnosis, the classifications were as follows: clinically established (n=45; 66.2%); clinically probable (n=12; 17.6%); possible prodromal (n=4; 5.9%); and negative (n=7; 10.3%). At the final evaluation, the classifications were as follows: clinically established (n=52; 76.5%); clinically probable (n=9; 13.2%); possible prodromal (n=2; 2.9%); and negative (n=5; 7.4%). Conclusions We were able to clarify the changes in the criteria values and transition of patients due to the clarification of imaging and supportive findings in the MDS criteria.

In a world increasingly confronted by cardiovascular diseases (CVDs) and an aging population, accurate risk assessment prior to cardiac surgery is critical. Although effective, traditional risk calculators such as the Japan SCORE, Society of Thoracic Surgeons score, and EuroSCORE II may not completely capture contemporary risks, particularly due to emerging factors such as frailty and sarcopenia. These calculators often focus on regional and ethnic specificity and rely heavily on evaluations based on age and underlying diseases. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that has been identified as a potential biomarker for sarcopenia and a tool for future cardiac risk assessment. Preoperative plasma GDF-15 levels have been associated with preoperative, intraoperative, and postoperative factors and short- and long-term mortality rates in patients undergoing cardiac surgery. Increased plasma GDF-15 levels have prognostic significance, having been correlated with the use of cardiopulmonary bypass during surgery, amount of bleeding, postoperative acute kidney injury, and intensive care unit stay duration. Notably, the inclusion of preoperative levels of GDF-15 in risk stratification models enhances their predictive value, especially when compared with those of the N-terminal prohormone of brain natriuretic peptide, which does not lead to reclassification. Thus, this review examines traditional risk assessments for cardiac surgery and the role of the novel biomarker GDF-15. This study acknowledges that the relationship between patient outcomes and elevated GDF-15 levels is not limited to CVDs or cardiac surgery but can be associated with variable diseases, including diabetes and cancer. Moreover, the normal range of GDF-15 is not well defined. Given its promise for improving patient care and outcomes in cardiovascular surgery, future research should explore the potential of GDF-15 as a biomarker for postoperative outcomes and target therapeutic intervention., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Acute embolic occlusion of the common carotid artery (CCA) alone is rare. However, once it occurs, recanalization is challenging due to the large volume of the clot, larger diameter of the CCA, and risk of procedure-related distal embolism into the intracranial arteries., Observations: The authors report two cases of acute embolic occlusion of CCA alone, caused by a cardiac embolus trapped at the proximal end of a preexisting atherosclerotic plaque at the cervical carotid bifurcation. In both cases, the CCA was successfully recanalized using retrograde thrombectomy in a hybrid operating room. In case 1, a 78-year-old male with acute right CCA occlusion underwent retrograde thrombectomy, where the cervical carotid bifurcation was exposed and incised, and the entire embolus was retrieved with forceps. Despite successful revascularization, massive bleeding from the CCA just after the retrieval remained a concern. In case 2, a 79-year-old female with acute right CCA occlusion underwent retrograde thrombectomy in the same manner. Because manual retrieval failed, a Fogarty balloon catheter inserted from the arteriotomy successfully retrieved the entire thrombus with minimal blood loss., Lessons: Retrograde thrombectomy through the arteriotomy of the cervical carotid bifurcation safely and effectively recanalizes acute embolic occlusion of the CCA alone.

Background: Dopamine transporter single-photon emission computed tomography (DAT-SPECT) is a crucial tool for evaluating patients with Parkinson's disease (PD). However, its implication is limited by inter-site variability in large multisite clinical trials. To overcome the limitation, a conventional prospective correction method employs linear regression with phantom scanning, which is effective yet available only in a prospective manner. An alternative, although relatively underexplored, involves retrospective modeling using a statistical method known as "combatting batch effects when combining batches of gene expression microarray data" (ComBat)., Methods: We analyzed DAT-SPECT-specific binding ratios (SBRs) derived from 72 healthy older adults and 81 patients with PD registered in four clinical sites. We applied both the prospective correction and the retrospective ComBat correction to the original SBRs. Next, we compared the performance of the original and two corrected SBRs to differentiate the PD patients from the healthy controls. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC)., Results: The original SBRs were 6.13 ± 1.54 (mean ± standard deviation) and 2.03 ± 1.41 in the control and PD groups, respectively. After the prospective correction, the mean SBRs were 6.52 ± 1.06 and 2.40 ± 0.99 in the control and PD groups, respectively. After the retrospective ComBat correction, the SBRs were 5.25 ± 0.89 and 2.01 ± 0.73 in the control and PD groups, respectively, resulting in substantial changes in mean values with fewer variances. The original SBRs demonstrated fair performance in differentiating PD from controls (Hedges's g  = 2.76; AUC-ROC = 0.936). Both correction methods improved discrimination performance. The ComBat-corrected SBR demonstrated comparable performance ( g  = 3.99 and AUC-ROC = 0.987) to the prospectively corrected SBR ( g  = 4.32 and AUC-ROC = 0.992) for discrimination., Conclusion: Although we confirmed that SBRs fairly discriminated PD from healthy older adults without any correction, the correction methods improved their discrimination performance in a multisite setting. Our results support the utility of harmonization methods with ComBat for consolidating SBR-based diagnosis or stratification of PD in multisite studies. Nonetheless, given the substantial changes in the mean values of ComBat-corrected SBRs, caution is advised when interpreting them., 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 Wakasugi, Takano, Abe, Sawamoto, Murai, Mizuno, Matsuoka, Yamakuni, Yabe, Matsuda, Hanakawa and Parkinson’s and Alzheimer’s disease Dimensional Neuroimaging Initiative (PADNI).)

Background and Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread all over the world. To assess the influence of the COVID-19 pandemic on emergency medical services (EMS) for vulnerable patients transported by ambulance. Materials and Methods: This study was a retrospective, descriptive study with a study period from 1 January 2019 to 31 December 2021 using the Osaka Emergency Information Research Intelligent Operation Network (ORION) system. We included all pediatric patients, pregnant women, and elderly patients ≥ 65 years of age transported by ambulance in Osaka Prefecture. The main outcome of this study was difficult-to-transport cases. We calculated the rate of difficult-to-transport cases under several conditions. Results : For the two year-long periods of 1 January 2019 to 31 December 2019 and 1 January 2021 to 31 December 2021, a total of 887,647 patients were transported to hospital by ambulance in Osaka Prefecture. The total number of vulnerable patients was 579,815 (304,882 in 2019 and 274,933 in 2021). Multivariate logistic regression analysis showed that difficult-to-transport cases were significantly more frequent in 2021 than in 2019. Difficult-to-transport cases were significantly less frequent in the vulnerable population than in the non-vulnerable population (adjusted odds ratio 0.81, 95% confidence interval 0.80-0.83; p < 0.001). Conclusion : During the pandemic (2021), difficult-to-transport cases were more frequent compared to before the pandemic (2019); however, vulnerable patients were not the cause of difficulties in obtaining hospital acceptance for transport.

Objective: The unified multiple system atrophy rating scale (UMSARS) was used to evaluate various symptoms of multiple system atrophy (MSA). And UMSARS part 1 was originally developed for use in interviews, but the need for telemedicine is increasing in COVID-19 pandemic. The purpose of this study is to evaluate the reliability of the UMSARS part 1 telephone survey., Methods: Thirty-two MSA patients took the UMSARS part 1 face-to-face, followed by two more telephone evaluations. Intraclass correlation coefficients (ICC) and Cronbach's alpha (α) coefficients were calculated, and the inter-rater reliability was determined. At the same time, we asked about the problems in COVID-19 pandemic., Results: The study participants included 15 men and 17 women with mean age of 67.1 years (SD, 8.3). For the total UMSARS part 1 score, the inter-rater ICC and Cronbach's α coefficient were 0.89 to 0.92, and 0.84 to 0.87, respectively. More than half of the items had a relatively high ICC. Cronbach's α coefficients were more than 0.7 for all items. Changes that occurred in COVID-19 pandemic included reduced outings and lack of rehabilitation in about half of the cases., Conclusion: The UMSARS part 1 has high inter-rater reliability and internal consistency. Evaluation of subjective symptoms showed that some variability could occur. In addition, there was concern about the influence of lack of rehabilitation due to COVID-19 pandemic., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The novel corona virus (COVID-19) pandemic occurred worldwide. Although an excessive burden was placed on emergency medical institutions treating urgent and severe patients, its impact on patient outcome remains unknown. This study aimed to assess the impact of the COVID-19 pandemic in 2021 on the emergency medical services (EMS) system and patient outcomes in Osaka Prefecture, Japan., Methods: This was a retrospective descriptive study with a study period from January 1, 2019 to December 31, 2021. We included patients who were transported by ambulance and had cleaned data that was recorded in the ORION system. The study endpoints were the number of patients transported by ambulance and the number of deaths among these patients in each month. To assess the impact of the COVID-19 pandemic on the EMS system, the incidence rate ratio (IRR) and 95% confidence interval (CI) were calculated using 2019 as the reference year. Mortalities were evaluated based on deaths in the emergency department and deaths at 21 days after hospitalization., Results: The numbers of patients transported by ambulance were 500,194 in 2019, 443,321 in 2020 (IRR: 0.88, 95% CI: 0.87-0.88), and 448,054 in 2021 (IRR: 0.90, 95% CI: 0.89-0.90). In 2019, the number of patients transported by ambulance and who died in the emergency departments was 4,980, compared to 5,485 in 2020 (IRR: 1.10, 95% CI; 1.06-1.44) and 5,925 in 2021 (IRR: 1.19, 95% CI: 1.15-1.24). In 2019, the number of patients who died within 21 days after hospitalization was 11,931, compared to 11,913 in 2020 (IRR; 1.00, 95% CI; 0.98-1.03) and 13,376 in 2021 (IRR; 1.12, 95% CI; 1.09-1.15)., Conclusion: The COVID-19 pandemic decreased the number of ambulance requests and worsened mortality of patients transported by ambulance in Osaka Prefecture during 2021., 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 Katayama, Tanaka, Domi, Masui, Nakao, Tachino, Hirose, Kitamura, Oda and Matsuoka.)