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We report the first large-scale retrospective cohort study on adolescent and young adult (AYA) polycythemia vera (PV) and essential thrombocythemia (ET) in Japan, a subgroup analysis using Japanese multicenter registry data (JSH-MPN-R18). This study included patients with PV (n = 31) or ET (n = 141) aged 20 to 39 years at the initial visit. Hemorrhage-free survival (HFS) was better in AYA ET than in non-AYA ET (5-year HFS: 100% vs. 88.6%, p < 0.01), which might be attributed to differences in antithrombotic treatment rates between AYA and non-AYA patients. Although thrombosis-free survival did not differ statistically, the percentage of venous thrombotic events (TEs) among total TEs was higher in AYA compared to non-AYA PV and ET in Japan (26.0% vs. 6.0%, p < 0.01), but much lower than figures reported in European or US cohorts. Cytoreductive therapy (CRT) was administered to 25.8% of AYA patients with PV and 43.3% of AYA patients with ET, and the reason was usually unrelated to high risk of thrombosis. These results could be used to develop a more appropriate strategy for managing PV and ET in the Japanese AYA population., Competing Interests: Declarations. Conflict of interest: YS reports honoraria from PharmaEssentia Japan K.K., Novartis Pharmaceutical, and research funds under contract from Incyte Biosciences Japan and Toyo Kohan K.K. KN reports research funds from Takeda Pharmaceutical internationals. KO reports research funds under contract from PharmaEssentia Japan K.K. and Abbvie Inc. TI reports honoraria from Novartis Pharmaceutical, Sanofi, and Takeda Pharmaceutical, and honoraria and grants from Abbvie Inc. and Bristol-Myers Squibb. AG reports grants from Eisai Co. Ltd., Ono Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Nippon Shinyaku Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD K.K., Otsuka Pharmaceutical Co. Ltd., Sumitomo Pharma Co. Ltd., Bayer Yakuhin Ltd., Daiichi Sankyo Co. Ltd., Nihon Pharmaceutical Co. Ltd. and honoraria from Novartis Pharma K.K., Alexion Pharmaceuticals Inc., Eisai Co. Ltd., Ono Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Nippon Shinyaku Co. Ltd., Chugai Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Daiichi Sankyo Co. Ltd., Nihon Pharmaceutical Co. Ltd., Kyowa Kirin Co. Ltd., Janssen Pharmaceutical K.K., Pfizer Japan Inc., Sanofi K.K., and PharmaEssentia Japan K.K. MN reports research funds from Veritas Corporation and honoraria to her spouse from Amgen Inc., Astellas Pharma, AstraZeneca plc., Bristol-Myers Squibb, Daiichi Sankyo, Janssen Pharmaceutical K.K., Meiji Seika Pharma Co. Ltd., Nippon Shinyaku, Novartis Pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Pharma, and Takeda Pharmaceutical. FK reports grants from Takeda Pharmaceutical, Janssen Pharmaceutical K.K., Chugai Pharmaceutical, AstraZeneca K.K., AbbVie GK, Kissei Pharmaceutical, and Sanofi K.K. KK reports honoraria from Novartis Pharmaceutical, Takeda Pharmaceutical, and PharmaEssentia Japan. HW reports grants from Chugai Pharmaceutical, Kyowa Kirin, Ono Pharmaceutical, and Takeda Pharmaceutical. KU reports research funds under contract from Astellas, Aperis, Celgene, Daichi Sankyo, MSD, Pfizer, and Yakult; honoraria under contract from Alnylam Japan and SOBI; and honoraria and research funds under contract from Novartis, Abbvie, Alexion, Amgen, Asahi Kasei Pharma, AstraZeneca, Bristol-Myers Squibb, Chugai, Eisai, Incyte, Kyowa-Kirin, Meiji Seika Pharma, Nippon-Shinyaku, Ohara, Ono, Otsuka, PharmaEssentia, Sanofi, Takeda, and Janssen. TM reports honoraria from Pfizer, Novartis Pharmaceutical, Takeda Pharmaceutical, and PharmaEssentia Japan, and research funds under contract from Asahi Kasei Pharma, Chugai Pharmaceutical, Kyowa Kirin, Eisai Pharmaceutical, JCR Pharmaceuticals, Abbvie Inc., Sumitomo Pharma, CSL Behring, Japan Blood Products Organization, and Otsuka Pharmaceutical. KS reports honoraria from Bristol-Myers Squibb, Celgene, Novartis Pharmaceutical, and Takeda Pharmaceutical; research funds under contract from PharmaEssentia Japan K.K.; and grants from Abbvie Inc., Astellas Pharma, Chugai Pharmaceutical, Kyowa Kirin, and MSD. AT reports honoraria from Takeda Pharmaceutical, research funds under contract from Kyowa Kirin, Novartis Pharmaceutical, Ono Pharmaceutical, Perseus Proteomics Inc., Pfizer, and Taiho Pharmaceutical and honoraria and research funds under contract from Chugai Pharmaceutical. YE reports research funds under contract from Meiji Seika Pharma and an endowed chair funded by PharmaEssentia Japan K.K. YH reports honoraria from Takeda Pharmaceutical and Novartis Pharmaceutical, and an endowed chair funded by PharmaEssentia Japan K.K. KA reports honoraria from Celgene and Novartis Pharmaceutical, grants from Asahi Kasei Pharma, Mochida, MSD, Mundi Pharma, Nippon Shinyaku Pharmaceutical, Ono Pharmaceutical, Shionogi, Sanofi, Sumitomo Dainippon Pharma, Taiho Pharmaceutical, Toyama Chemical, Shin Nippon Biomedical Laboratories, Yakult Honsha, and Takeda Pharmaceutical; honoraria and research funds under contract from Bristol-Myers Squibb and Janssen Pharmaceutical; honoraria and grants from Abbvie Inc., Chugai Pharmaceutical, and Eisai Pharmaceutical; research funds under contract and grants from Daiichi Sankyo and Otsuka Pharmaceutical, honoraria, research funds under contract; and grants from Astellas Pharma and Kyowa Kirin. IM received speakers bureau fees from Pfizer Japan Inc., Ono Pharmaceutical Co. Ltd., Novartis Pharma K.K., Chugai Pharmaceutical Co. Ltd., AbbVie G.K., Janssen Pharmaceutical K.K., Bristol-Myers Squibb K.K. (Celgene K.K.), AstraZeneca K.K., and Otsuka Pharmaceutical Co. Ltd. and received research funding from Chugai Pharmaceutical Co. Ltd., Kyowa Kirin Co. Ltd., Sumitomo Pharma Co. Ltd., Nippon Shinyaku Co. Ltd., Eisai Co. Ltd., Asahi Kasei Pharma Corp., AbbVie G.K., Taiho Pharmaceutical Co. Ltd., and received consultancy fees from Otsuka Pharmaceutical Co. Ltd. KT reports honoraria from Novartis Pharmaceutical and MSD; grants from Astellas Pharma, Chugai Pharmaceutical, and Otsuka Pharmaceutical; and honoraria and grants from Kyowa Kirin. NK has received a salary from PharmaEssentia Japan, where he is a board member; reports honoraria from Abbvie Inc., Celgene, and Japan Tobacco Inc.; research funds under contract from FUJIFILM Wako Chemicals, Fuso-pharm, Meiji Seika Pharma, Perseus Proteomics Inc., and Pfizer, grants from Bristol-Myers Squibb, Chugai Pharmaceutical, Kyowa Kirin, and Sumitomo Dainippon Pharma; honoraria and grants from Novartis Pharmaceutical and Otsuka Pharmaceutical; and honoraria, research funds under contract, and an endowed chair funded by PharmaEssentia Japan K.K. The other authors declare no competing interests., (© 2024. Japanese Society of Hematology.)

Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common monogenic cerebral small vessel diseases. Our previous observational study suggested that lomerizine hydrochloride, a calcium channel blocker approved in Japan in 1999 for the prevention of migraine headaches, is also effective for preventing recurrent ischemic stroke in CADASIL patients. The aim of this study (LOMCAD trial) is to verify the efficacy of lomerizine hydrochloride., Materials and Methods: This is a multicenter, prospective, single-arm trial, using a historical control for comparison. CADASIL patients with a history of two or more cerebral ischemic events within the last two years will be administered lomerizine hydrochloride (5-mg tablet twice daily) for 24 months. The primary endpoint is symptomatic cerebral ischemic events during the 24-month period. Using our historical data and Bayesian sample size calculation based on a prior predictive distribution, the planned sample size was determined as 20 subjects., Conclusion: We have planned a clinical trial to verify the effectiveness of lomerizine hydrochloride as prophylaxis to prevent recurrent cerebral ischemic events in CADASIL patients., Registration: The LOMCAD trial has been registered in the Japan Registry of Clinical Trials (jRCTs051220072, https://jrct.niph.go.jp/latest-detail/jRCTs051220072)., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to this study., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To investigate the association between acute pain trajectory over one week and patient-reported outcomes (PRO) at 6-months following lumbar surgery in patients with lumbar degenerative disease (LDD)., Methods: Two hundred and fifty-five subjects with LDD who received surgical treatment at our hospital between April 2019 and March 2022. Acute pain trajectory was measured using a pain trajectory calculator to determine an approximate line using the linear least squares method based on pain intensity on postoperative days 1, 3, 5, and 7. The pain trajectory-slope, which represents the change in postoperative pain intensity of the calculated approximation line, was evaluated as the main exposure for the present study. The PRO was assessed using the Oswestry Disability Index (ODI) measured at 6 ± 1 months postoperatively. Poor PRO scores in this study were defined using a threshold of an ODI of 22% or greater, which represents the patient acceptable symptomatic state after lumbar spine surgery. Multivariable logistic regression analysis including covariates was performed to investigate the association between pain trajectory-slope and PRO at 6-months following lumbar surgery., Results: In this study, 101 (39.6%) had poor PRO scores. Multivariable logistic regression analysis adjusted for covariates showed that pain trajectory-slope was associated with the poor PRO scores (odd ratios; 1.203, 95% confidence intervals; 1.130-1.288)., Conclusions: The results of this study show that acute pain trajectory is significantly associated with poor PRO scores 6-months after lumbar surgery. Patients with slower pain relief or worsening pain were associated with poor PRO scores., Competing Interests: Declaration. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Kidney transplant (KT) requires long-term glucocorticoid (GC) treatment against acute and/or chronic rejection. Glucocorticoid-induced osteoporosis (GIOP) is one of the major concerns in kidney transplant recipients (KTRs). Therefore, it is essential to accumulate GIOP data from paediatric KTRs to aid in their healthy growth. A serial observational study of bone strength was carried out in an 8-year-old girl with bilateral hypoplastic kidney who underwent ABO-compatible living-donor KT and GC treatment over 2 years. Bone strength was evaluated by bone mineral density (BMD) and serum bone turnover markers (BTMs), including serum alkaline phosphatase (S-ALP), serum tartrate-resistant acid phosphatase 5b (S-TRACP-5b), and serum undercarboxylated osteocalcin (S-ucOC). All the levels of BTMs and BMD from 1 M to 4 M remained lower than the levels at 0 months (0 M: baseline). After gradual reduction of GC dose (4 M-24 M), S-ALP levels increased from baseline and S-TRACP-5b levels remained lower than the baseline level, but BMD recovered to baseline and increased. The S-ucOC levels did not increase from baseline. The patient's height growth velocity SDS was +3.99 for 23 months, and no fracture occurred during this observation period. A consistent, predominantly formative state of bone, which maintained higher S-ALP levels and lower S-TRACP-5b levels compared to baseline, could contribute to increased BMD. In addition, no increase in S-ucOC levels from baseline could be associated with no deterioration of bone strength. This case suggests that measurement of BMD and, S-ALP, TRACP-5b and ucOC could be useful for evaluating the trend on bone strength in a paediatric KTR., (© 2024 Asian Pacific Society of Nephrology.)

This study aims to investigate the effects of neuromuscular electrical stimulation (NMES) in addition to conventional early mobilization in the early postoperative period after living donor liver transplantation (LTx) on body composition and physical function. This was a retrospective single-center cohort study. Adult subjects who were admitted for living donor LTx from 2018 to 2023 were included in the analysis. After April 2020, patients underwent 4 weeks of NMES in addition to conventional rehabilitation. The skeletal muscle mass index, body cell mass, and physical function, including the 6-minute walking distance, were assessed before surgery and at discharge, and changes in these outcomes were compared before and after the introduction of NMES. Sixty-one patients were in the NMES group, and 53 patients before the introduction of NMES were in the control group. ANCOVA with etiology, obstructive ventilatory impairment, Child-Pugh classification, and initial body composition value as covariates demonstrated that there was a significantly smaller decline of body cell mass (-2.9±2.7 kg vs. -4.4±2.7 kg, p = 0.01), as well as of the skeletal muscle mass index (-0.78±0.73 kg/m 2 vs. -1.29±1.21 kg/m 2 , p = 0.04), from baseline to discharge in the NMES group than in the control group; thus, the decline after surgery was suppressed in the NMES group. Four weeks of NMES, in addition to conventional rehabilitation in the early period after LTx, may attenuate the deterioration of muscle mass. It is suggested that NMES is an option for developing optimized rehabilitation programs in the acute postoperative period after LTx., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Activated arginine vasopressin (AVP) pathway worsens congestion in heart failure (HF), but its potential to relieve pulmonary congestion is also reported. The pathophysiological role and prognostic utility of AVP elevation in acute decompensated HF (ADHF) are poorly understood. We prospectively enrolled 52 hospitalized patients for ADHF to investigate the association between acute lung injury (ALI) in ADHF and AVP levels on admission. ALI was defined as respiratory failure leading to death, or requiring a respirator or a more than 12-h non-invasive intermittent positive pressure ventilation (NIPPV) support. In addition, we investigated the prognostic value of AVP levels on admission for cardiovascular death or recurrence of ADHF after discharge. ALI was documented in 7 patients (13.5%) during a median hospital stay of 14 days. And the patients with ALI demonstrated significantly higher AVP levels than those without (32.5 ± 21.6 vs. 6.4 ± 8.7 pg/ml, p = 0.018). Besides, the patients with ALI demonstrated significantly higher heart rates (HR) and lower E/e' on admission (HR: 127 ± 24 vs. 97 ± 28 bpm; E/e': 10.6 ± 3.7 vs. 17.4 ± 6.2, all p < 0.05, respectively). Of note, significant hemodilution assessed by hemoglobin and hematocrit values were observed in the patients with ALI 48 h after admission. A receiver operating characteristic curve analysis showed that higher than 7.2 pg/ml surrogate ALI in ADHF (AUC: 0.897, p = 0.001, Sensitivity: 85.7%, and Specificity: 77.8%). In contrast, increased AVP levels on admission could not predict cardiovascular events after discharge. Elevated AVP levels on admission are associated with ALI in ADHF but not cardiovascular events after discharge., Competing Interests: Declarations Conflict of interest The authors have no other financial relationship with any commercial entity interested in this manuscript's subject, and all authors declare no potential conflicts., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Virome analysis was performed on 174 grape genetic resources from the National Agriculture and Food Research Organization, Japan. A total of 20 bulk samples was prepared by grouping the vines into batches of 6-10 plants. Each of the bulk samples was analyzed using high-throughput sequencing, which detected 27 viruses and 5 viroids, including six viruses and one viroid reported in Japan for the first time (grapevine viruses F, L, and T, grapevine Kizil Sapak virus, grapevine Syrah virus 1, grapevine satellite virus, and grapevine yellow speckle viroid 2). In addition, a novel vitivirus was detected with a maximum nucleotide sequence identity of only 58% to its closest relative, grapevine virus A (GVA). The genome of this novel virus was 7,461 nucleotides in length and encoded five open reading frames showing the typical genomic structure of vitiviruses. Phylogenetic trees of vitiviruses placed it in a distinct position nearest to GVA or grapevine virus F (GVF) in genomes and amino acids of deduced replication-associated protein (RAP) and coat protein (CP). The amino acid sequence identities of RAP and CP with GVA, GVF, and other vitiviruses were a maximum of 53% and 73%, respectively, which were significantly below the species demarcation threshold of 80% in the genus. The low identity and phylogenetic analyses indicate the discovery of a novel vitivirus species provisionally named grapevine virus P., Competing Interests: Declarations Conflict of interest The author belongs to NARO. The author has no conflict of interest. Research involving human participants and animals This article does not contain any studies with human participants or animals performed by the author., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: H. Inoue has received grants from Olympus Corporation and Takeda Pharmaceutical Company and is an advisor for Olympus Corporation and Top Corporation. D. Shiomi, K. Sumi, Y. Kawasaki, N. Nomura, J. Ushio, and T. Ito declare that they have no conflicts of interest.

Computer-aided design-computer-aided manufacturing (CAD-CAM) systems have been widely used as a fabrication method for restorations because of their high efficiency and accuracy, which significantly reduces fabrication time. However, molars with insufficient clearance or short clinical crown lengths require retention holes or grooves on the preparation, making it difficult to replicate the shapes with the CAM milling system. In these cases, restorations using the lost-wax method are selected. This article focuses on one-piece endodontic crowns (endocrowns) fabricated with a CAD-CAM system (CAD-CAM endocrowns), in which their posts and crowns are integrated. Articles from July 2012 to August 2023 were searched in PubMed with the keyword "endocrown". This review discusses the application of CAD-CAM endocrowns to molars from the viewpoint of model experiment (fracture resistance, adaptation) and clinical research. This technique, which allows margins and internal gaps to be set within the clinically acceptable range, is reported to be an effective way of restoring molars with high survival rates in clinical research., Competing Interests: All authors declare that they have no conflicts of interest in regard to this work., (© 2024 The Authors.)

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants that have been used for various purposes. Although PFAS can pollute the environment in a variety of areas related to the use, storage, and disposal of their products, there are insufficient data on the extent of PFAS pollution outside industrialized countries with their manufacturing facilities. Most of the analyses depend on high-cost liquid chromatography-tandem mass spectrometry. In this study, we established a method to analyze ionic PFAS using gas chromatography-electron impact ionization-mass spectrometry with in-port arylation by diaryl iodonium. Extraction of PFAS from water samples was performed using solid phase extraction with reverse phase sorbent. Fourteen PFAS compounds could be detected from spiked water samples, and the detection limit ranged from 3.1 to 8.1 ng L -1 . Using this method, we analyzed groundwater samples from Okinawa Island, Japan, and detected PFAS up to a total concentration of 1900 ng L -1 . This method uses relatively inexpensive analytical equipment; hence, it can possibly enable surveys on PFAS contaminations in a wide range of regions and opportunities., Competing Interests: Declarations. Ethical approval: Not applicable Consent to participate: Not applicable Consent for publication: Not applicable Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The only treatment for non-resectable colorectal liver metastasis (CRLM) is medical therapy, and the overall survival (OS) rate at 3 and 5 years is approximately 30%-40% and less than 10%, respectively. In 2020, a group in Norway reported that liver transplantation for non-resectable CRLM improved the 5-year OS rate to up to 83%. Clinical trials have been launched since that report was published, but most have involved deceased-donor liver transplantation rather than living-donor liver transplantation. Our study will assess the efficacy and safety of living-donor liver transplantation for patients with non-resectable CRLM., Methods and Analysis: This is an investigator-driven, multicentre, prospective, single-arm study involving 11 university hospitals in Japan. Patients with non-resectable CRLM and resected primary cancers will be enrolled in the study. Any patients with histopathological or genetic mutations, such as those of RAS and BRAF, are eligible. Furthermore, patients who underwent lung treatment for three or fewer pulmonary metastases and experienced no recurrence for more than 6 months are eligible. The eligibility of the candidates will be reviewed by the Central Eligibility Review Committee. The primary endpoint is the 3-year OS rate. Assuming an OS rate of 70% and a threshold of 45%, the number of required patients is 23, with an alpha error of 5% (one-sided), power of 80% and a 10% dropout rate., Ethics and Dissemination: Ethical approval was obtained from the ethical review board of Kyoto University (R-1591). All participants are required to provide written informed consent. The results will be submitted for publication in a peer-reviewed journal., Trial Registration Number: jRCT1050230053 and UMIN000049785., Competing Interests: Competing interests: None declared., (© 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.)

Transcatheter aortic valve implantation (TAVI) is a proven treatment for severe aortic stenosis (AS); however, the effects of TAVI on central blood pressure (CBP) and clinical outcomes remain unclear. We assessed CBP indices before and after TAVI and their prognostic value. Seventy-six patients with severe AS who underwent TAVI were retrospectively evaluated, and CBP was estimated noninvasively 1 day before and after TAVI. The following indices were measured: augmentation index corrected for heart rate (HR) (AIx@HR75), peak pressure of the forward wave (Pf) and backward wave (Pb), time to peak pressure of the forward wave corrected for HR (Tfc) and the backward wave corrected for HR (Tbc), and ejection duration (ED). The primary endpoint was the composite outcome of all-cause mortality and hospitalized heart failure. The median follow-up period was 1135 (844-1404) days. Tfc, Tbc, ED, Pb, and AIx@HR75 decreased despite no significant changes in Pf after TAVI. The univariable Cox proportional hazards model showed that ED 1 day after TAVI was associated with composite outcomes (hazard ratio: 1.02; 95% confidence interval [CI]: 1.01-1.04; P = 0.002). When the patients were divided into two groups by the cutoff value determining composite outcomes by receiver operating characteristic curve analysis, a long ED 1 day after TAVI was significantly associated with composite outcomes by Kaplan-Meier curve analysis (log-rank test, P < 0.001). The multivariable Cox proportional hazards model showed that a long ED 1 day after TAVI was associated with composite outcomes (adjusted hazard ratio: 12.12; 95% CI 2.41-60.81; P = 0.002). In conclusion, a long ED 1 day after TAVI was associated with adverse clinical outcomes., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: Avelumab + axitinib was approved for advanced renal cell carcinoma (aRCC) in Japan in December 2019. We report long-term real-world outcomes with first-line avelumab + axitinib from the J-DART2 study in Japan., Methods: J-DART2 was a multicenter, noninterventional, retrospective study examining clinical data from patients with curatively unresectable locally advanced or metastatic RCC who started treatment with first-line avelumab + axitinib in Japan between December 2019 and October 2022. Endpoints included patient characteristics, treatment patterns, and outcomes., Results: Data from 150 patients across 19 sites were analyzed; median follow-up was 18.7 months (95% CI, 16.3-20.6 months). Median age was 70.5 years; 26.0% of patients were aged ≤64 years, 42.7% were aged 65-74 years, and 31.3% were aged ≥75 years. International Metastatic RCC Database Consortium risk was favorable in 26.0%, intermediate in 54.7% (1 risk factor in 30.7%; 2 risk factors in 24.0%), and poor in 19.3% of patients. Median progression-free survival (PFS) was 17.1 months, with 1- and 2-year PFS rates of 57.7% and 37.5%, respectively. Median overall survival (OS) was not reached, with 1- and 2-year OS rates of 90.6% and 84.7%, respectively. Objective response rate was 53.3%; disease control rate was 88.9%. Outcomes were similar across age groups, including patients aged ≥75 years., Conclusions: J-DART2 is the largest retrospective study to report long-term real-world outcomes in patients with aRCC treated with avelumab + axitinib in Japan. Findings were similar to those observed in previous studies and support the benefit of avelumab + axitinib in clinical practice in Japan., Competing Interests: Declarations Conflict of interest T. Kato has received honoraria for lectures from MSD. J. Furukawa has received honoraria for lectures from Merck and Ono Pharmaceutical. N. Hinata has received honoraria for lectures from AstraZeneca, Bayer Yakuhin, Bristol Myers Squibb, Kissei Pharmaceutical, MSD, Sanofi, Sysmex, and Takeda. K. Ueda has received honoraria for lectures from Merck and MSD. I. Hara has received honoraria for lectures from Astellas Pharma, Janssen, and Takeda and has received research funding from Bristol Myers Squibb. F. Hongo has received honoraria for lectures from Merck, MSD, Pfizer, and Takeda. R. Mizuno has received honoraria for lectures from Merck and Takeda. T. Okamoto and H. Okuno have nothing to disclose. T. Ito and M. Kajita report employment with Merck Biopharma Co., Ltd., Tokyo, Japan, an affiliate of Merck KGaA. M. Oya has received honoraria from Bayer, Bristol Myers Squibb, Eisai, Merck Biopharma Co., Ltd., Tokyo, Japan, an affiliate of Merck KGaA, MSD, Ono Pharmaceutical, Pfizer, and Takeda; and has received scholarship endowments from Bayer, Eisai, and Takeda. Y. Tomita has participated in consulting or advisory roles for Eisai, MSD, and Ono Pharmaceutical; has received honoraria from Astellas Pharma, Bristol Myers Squibb Japan, Chugai Pharma, Novartis, Ono Pharmaceutical, and Pfizer; and has received research funding from Astellas Pharma, AstraZeneca, Chugai Pharma, Eisai, MSD, Novartis, Ono Pharmaceutical, Pfizer, and Takeda. N. Shinohara has received grants or contracts from Bristol Myers Squibb, Ono Yakuhin, and Takeda; has received honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bristol Myers Squibb, MSD, Novartis, Ono Yakuhin, Pfizer, and Takeda; and is the president of the Japanese Society of Renal Cancer. M. Eto has received research funding from Takeda Pharmaceutical; and has received honoraria for lectures from Astellas Pharma, AstraZeneca, Bayer Yakuhin, Bristol Myers Squibb, Eisai, Janssen Pharmaceutical, Merck Biopharma, MSD, Ono Pharmaceutical, Pfizer, and Takeda Pharmaceutical. H. Uemura has received research grants from Astellas, AstraZeneca, Janssen, Ono Pharmaceutical, Taiho, and Takeda; has received consulting fees from Ono Pharmaceutical and Sanofi; has received payment or honoraria for lectures and speakers’ bureaus from Bayer, Janssen, MSD, Pfizer, Sanofi, and Takeda; and has received payment for expert advisory testimony from AstraZeneca, Ono Pharmaceutical, and Sanofi., (© 2024. The Author(s).)

Gastroenteropancreatic neuroendocrine tumors (NET) often metastasize to the liver. Although curative liver resection provides a favorable prognosis for patients with neuroendocrine liver metastasis (NELM), with a 5-year survival rate of 70-80%, recurrence is almost inevitable, mainly in the remnant liver. In Western countries, liver transplantation (LT) has been performed in patients with NELM, with the objective of complete removal of macro- and micro-NELMs. However, prognosis had been unsatisfactory, with 5-year overall survival and recurrence-free survival rates of approximately 50 and 30%, respectively. In 2007, the Milan criteria were proposed as indications for LT for NELM. The criteria included: (1) confirmed histology of NET-G1 or G2; (2) a primary tumor drained by the portal system and all extrahepatic diseases removed with curative resection before LT; (3) liver involvement ≤50%; (4) good response or stable disease for at least 6 months before LT; (5) age ≤ 55 years. A subsequent report demonstrated outstanding LT outcomes for NELM within the Milan criteria, with 5-year overall survival and recurrence rates of 97 and 13%, respectively. In Japan, living donor LT (LDLT) for NELM has been performed sporadically in only 16 patients by 2021 in Japan; however, no consensus has been reached on the indications or perioperative management of LDLT. This article presents the outcomes of these 16 patients who underwent LDLT in Japan and reviews the literature to clarify optimal indications and perioperative management of LDLT for NELM in the era of novel multimodal treatments., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest., (© 2024. The Author(s).)

Objective: Tocilizumab (TCZ) is effective for giant cell arteritis (GCA). However, little is known regarding treatment modification and clinical outcomes after unfavorable events, such as GCA relapses or TCZ discontinuation due to adverse events (AEs)., Methods: This multicenter retrospective study included GCA patients who initiated TCZ from 2008 to 2021 at five Japanese hospitals. GCA relapses and TCZ-related AEs were monitored for two years after TCZ initiation. In patients with GCA relapses, subsequent clinical courses, including relapse symptoms and treatment modification, were followed for 90 days after the relapses. Similarly, patients who discontinued TCZ due to AEs were additionally followed until one year after the TCZ discontinuation to evaluate AEs, relapses, and treatment changes., Results: Of 62 eligible patients, 10 patients (16%) relapsed after initiating TCZ therapy. Most relapses (8/10) occurred after extending TCZ intervals or discontinuing TCZ. Combinations of adjusting TCZ intervals, glucocorticoid (GC), and/or methotrexate (MTX) could manage the relapses without serious complications. In the entire cohort, AEs occurred in 28 patients (45%), and 8 patients (13%) discontinued TCZ due to AEs. After AE-related TCZ discontinuation, six patients attempted to taper GC without other immunosuppressive treatments, and four subsequently relapsed. In contrast, two patients who used other immunosuppressants or biological therapy could decrease GC without relapses., Conclusion: Although GCA relapses can occur after initiating TCZ therapy, most relapses can be safely managed by adjusting TCZ, GC, and/or MTX. Adding immunosuppressants or biological treatments may potentially be related to preventing relapses when patients discontinue TCZ due to AEs.

Objective: This study aimed to measure and compare cerebrospinal fluid neuronal injury biomarkers in the acute phase of complex febrile seizure (CFS) and infection-triggered acute encephalopathy (AE). Furthermore, we determined the pathogenesis of AE with biphasic seizures and late reduced diffusion (AESD)., Methods: Pediatric patients with febrile status epilepticus who visited Hyogo Prefectural Kobe Children's Hospital from November 1, 2016, to December 31, 2022, and whose cerebrospinal fluid samples were collected within 24 h of neurological symptom onset were included. Patients were classified as having CFS or infection-triggered AE according to their definitions. Patients with AE were further categorized into AESD or unclassified AE. Cerebrospinal fluid biomarkers (neuron-specific enolase, growth differentiation factor 15 [GDF-15], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein, and tau protein were measured and compared among the groups., Results: Total of 63 patients (45 with CFS and 18 with AE) were included. Among the AE patients, nine were classified as having AESD and nine as having unclassified AE. S100B levels were significantly higher in patients with AESD than in patients with CFS (485 pg/ml vs. 175.3 pg/ml) and were even higher in patients with AESD and neurological sequelae (702.4 pg/ml). GDF-15 levels were significantly elevated in patients with AE compared to patients with CFS (85.8 pg/ml vs. 23.6 pg/ml)., Conclusions: The elevation of S100B suggests that activated astrocytes may be closely associated with the early pathology of AESD. Elevated GDF-15 levels in infection-triggered AE suggest the activation of defense mechanisms caused by stronger neurological injury., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A powder formulation for mucosal administration of mRNA-encapsulated lipid nanoparticles (mRNA-LNPs) is expected to be useful for respiratory diseases. Although freeze-drying is widely used to obtain solid formulations of mRNA-LNPs, highly hydrosoluble cryoprotectants, such as sucrose are necessary. However, sucrose is not a suitable excipient for inhalation powders because of its hygroscopic and deliquescence properties. Spray freeze-drying (SFD) is a method to produce inhalable powder formulation. In this study, we prepared inhalable powder formulations of mRNA-LNPs without deliquescence excipients using pH-modified SFD, which strengthens the interaction between mRNA and ionizable lipids of LNPs by acidic pH modifier, leading to retention of the encapsulated structure of mRNA-LNPs even after SFD. Powdered mRNA-LNPs were suitable for inhalation, and mRNA was encapsulated in LNPs after SFD. The mRNA encapsulation efficiency and mRNA transfection efficiency of pH-modified SFD-mediated powdered mRNA-LNPs were higher than those of conventional SFD, although they were significantly lower than those of liquid intact mRNA-LNPs. However, after long-term storage, the powdered formulation of the mRNA-LNPs exhibited higher mRNA transfection efficiency than liquid mRNA-LNP. Powdered mRNA-LNPs also exerted their function in air-liquid interface cultivation and in vivo intratracheal administration. Collectively, the powder formulation of mRNA-LNPs especially prepared by SFD is expected to be applied for dry powder inhalers., 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. Published by Elsevier B.V.)

The prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) is reported to be as worse as myocardial infarction with obstructive coronary arteries. However, its mechanical complications are still poorly understood. A 71-year-old woman developed MINOCA after ascending aortic replacement surgery. During treatment, the patient experienced cardiogenic shock due to a ventricular septal rupture (VSR). The introduction of Impella devices reduced the left-to-right shunt and improved the patient's hemodynamics. Finally, a scheduled surgical repair was performed under stable conditions. In this report, we focused on the pathophysiology of MINOCA-related VSR and discussed the effectiveness of Impella devices as a bridge to surgical repair and circulatory backup during the perioperative period.

RNA-dependent protein kinase (PKR) may have a positive regulatory role in controlling tumor growth and progression in hepatocellular carcinoma (HCC). However, the downstream substrates and the molecular mechanism of PKR in the growth and progression of HCC have not been clarified. In this study, mass spectrometry analysis was performed with immunoprecipitated samples, and 4.1R was identified as a protein that binds to PKR. In transfected COS7 cells, an immunoprecipitation experiment showed that 4.1R binds to wild-type PKR, but not to a kinase-deficient mutant PKR, suggesting that PKR binds to 4.1R in a kinase activity-dependent manner. In HCC cell lines, HuH7 and HepG2, the expression level of 4.1R protein was shown to be regulated by protein expression and activation of PKR. Interestingly, high expression of 4.1R, as well as PKR, is associated with a worse prognosis in HCC. PKR increased HCC cell growth in both anchorage-dependent and anchorage-independent manners, whereas 4.1R was involved in HCC cell growth only in an anchorage-independent manner, not in an anchorage-dependent manner. The rescue experiment indicated that increased anchorage-independent growth of HCC cells by PKR might be caused by 4.1R. In conclusion, PKR associates with 4.1R and promotes anchorage-independent growth of HCC. The PKR-4.1R axis might be a new therapeutic target in HCC., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The present study aimed to investigate the impact of cancer-associated thromboembolism (CAT) on the survival and biomarkers of ovarian clear cell carcinoma (OCCC). Patients with OCCC who underwent surgery at the National Defense Medical College Hospital (Tokorozawa, Japan) between January 2000 and December 2019 were included in the current study. Associations among CAT, clinicopathological features and prognosis were retrospectively compared. Furthermore, immunohistochemical staining was conducted in all patients to compare differences between patients with and without CAT. Among 111 patients with OCCC, 20 patients (18.0%) had CAT complications. CAT was detected in 12 patients (10.8%) before primary treatment and in 8 patients (7.2%) after primary surgery. Patients with CAT experienced more tumor recurrence (P=0.048) and platinum resistance (P=0.025), had worse progression-free survival (PFS; P<0.01) and overall survival (OS; P<0.01), and multivariate analysis showed that CAT was a prognostic factor for worse PFS [hazard ratio (HR)=2.10, P=0.039] and OS (HR=4.26, P<0.01). Moreover, immunohistochemical analysis revealed that more OCCC cases with CAT were positive for tissue factor (TF; P=0.030) and phosphorylated-Janus kinase 2 (JAK2; P=0.034) expression than those without CAT. In conclusion, CAT may be associated with platinum resistance and poor prognosis in patients with OCCC. Furthermore, TF and JAK2 could be considered potential novel therapeutic targets for OCCC complicated by CAT., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Ito et al.)

Purpose: To determine the morphology and incidence of peripheral drusen-like deposits (DLDs) in eyes with pathological myopia (PM) using ultra-widefield (UWF) fundus photographs and UWF optical coherence tomographic (OCT) images., Design: Retrospective, observational case series study., Method: We reviewed the medical records of 676 patients (1352 eyes) with high myopia (HM) who were examined in the Advanced Clinical Centre for Myopia between 2017 and 2021. The main outcome measures were the incidence and morphological characteristics of the DLDs in the peripheral retina detected by ultra-widefield (UWF) imaging devices., Results: Sixty-six of the 1352 (4.9%) eyes had peripheral DLDs. In 5 eyes, the DLDs were found at the staphyloma edge. The mean age of the patients was 70.0 ± 13.0 (range, 46.0-92.0) years, and the mean axial length was 29.8 ± 2.4 mm. Myopic macular neovascularization (MNV) was found in 41 of the 66 eyes with DLDs (62.1%). Patients with drusen in Zone 2 were significantly older than those in Zone 3 (80 ± 13 vs 64 ± 13 years; P < 0.001)., Conclusions: Ultra-widefield images showed that peripheral DLDs were present in 4.9% of highly myopic eyes. The findings in eyes with DLDs may provide a basis for the evaluations of the natural progression of peripheral retinal changes in eyes with PM., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Introduction: Malignant melanomas occur most commonly in the skin, mucous membranes, or choroid. Clitoral malignant melanomas are extremely rare. Stage IV malignant melanomas have a poor prognosis, and molecularly targeted agents or immune checkpoint inhibitors are recommended. However, surgical resection is reportedly a valid option for improving the prognosis of patients with oligometastases, defined as a small number of metastases that can be completely resected. In this report, we describe hepatic resection for a recurrent liver metastasis in a patient who had undergone removal of a clitoral malignant melanoma 9 years previously., Case Presentation: An 82 year-old woman presented with a black nodule on her clitoris. Total resection of the nodule resulted in a diagnosis of clitoral malignant melanoma (pT4bN0M0, pStage IIC; UICC 8th edition). A follow-up computed tomography scan 4 years later revealed a single 5 mm mass in the lower lobe of the right lung, prompting partial resection of the right lung. Pathological examination of the operative specimen revealed a pulmonary metastasis of malignant melanoma. The patient was treated with pembrolizumab monotherapy as adjuvant chemotherapy for 1 year. A follow-up computed tomography scan 9 years after surgical removal of the primary lesion revealed an 18 mm mass in segment II of the liver, prompting robot-assisted laparoscopic left lateral sectionectomy. The provisional diagnosis of metastatic malignant melanoma in the liver was confirmed by histopathological examination of the operative specimen. The patient was treated with pembrolizumab monotherapy as postoperative adjuvant chemotherapy for 1 year. No further recurrence was detected at the 1.5 year follow-up., Conclusion: We performed hepatectomy for oligometastasis of clitoral malignant melanoma, an extremely rare entity. Surgery has the potential to prolong the prognosis of patients with oligometastasis., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Aim: As aging populations shift health care from hospitals to communities, Japan has implemented policies to promote home health care. This study explored regional differences in home health care recipients among older adults and related factors., Methods: We used nationwide data from 2020 to describe the proportion of older adults receiving regular home visits and the medical institutions utilized across secondary medical areas: urban, middle and depopulated areas. We examined factors associated with the proportion of patients receiving regular home visits. Exposures included each secondary medical area's medical and long-term-care (LTC) resources, adjusted for the older adult population; proportion of single-person households; and regional factors. We performed a multivariate negative binomial distribution analysis., Results: A total of 333 secondary medical areas were included. Urban areas had more patients receiving regular home visits, primarily from enhanced home care support clinics/hospitals (HCSCs). Fewer patients received regular home visits in depopulated areas, and conventional HCSCs were more common. Multivariate analysis revealed that the number of conventional HCSCs (coefficient, 0.17 [95% confidence intervals (CI), 0.08 to 0.26]), enhanced HCSCs (coefficient, 0.21 [95% CI, 0.14 to 0.29]) and population density (coefficient, 0.10 [95% CI, 0.02 to 0.19]) were positively associated with higher home-visit rates. Beds in LTC welfare facilities (coefficient, -0.10 [95% CI, -0.19 to -0.01]) and beds in LTC health facilities (coefficient, -0.09 [95% CI, -0.17 to 0.00]) were negatively associated., Conclusions: Policies to promote home health care have led to high home-visit rates in urban areas. Medical and LTC resources and regional factors influence disparities. As Japan's population ages, it is crucial to recognize these disparities and develop medical and LTC systems tailored to each region's characteristics. Geriatr Gerontol Int 2024; ••: ••-••., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Background: Although the MADIT-ICD benefit score (MBS) helps select suitable implantable cardioverter defibrillator (ICD) candidates, optimal indicators for cardiac resynchronization therapy (CRT) remain uncertain. Evaluating the applicability of the MBS in Japanese CRT patients is imperative., Methods and Results: This multicenter study assessed the cumulative incidence of ventricular tachycardia/fibrillation (VT/VF) and non-arrhythmic mortality (AM) in CRT patients grouped according to potential benefit (lowest, highest, and intermediate). Among 400 primary prevention patients (mean age 65 years, 76% male), VT/VF occurred in 4 (7%), 68 (24%), and 14 (23%) patients in the lowest-, intermediate-, and highest-benefit groups, respectively (P=0.027), over a median follow-up of 34 months. Non-arrhythmic death was observed in 15 (25%), 91 (33%), and 9 (15%) patients in the lowest-, intermediate-, and highest-benefit groups, respectively (P=0.025). Multivariate analysis identified VT/VF score ≥7 (hazard ratio [HR] 2.14; 95% confidence interval [CI] 1.09-4.19; P=0.027) as a significant VT/VF predictor. The presence of left bundle branch block (HR 0.51; 95% CI 0.29-0.92; P=0.025) was associated with a reduced risk of VT/VF events. Non-AM score ≥3 (HR 1.70; 95% CI 1.01-2.88; P=0.047), systolic blood pressure <100 mmHg (HR 1.84; 95% CI 1.25-2.70; P=0.002), and estimated glomerular filtration rate <30 mL/min/1.73 m 2 (HR 1.98; 95% CI 1.23-3.20; P=0.005) were significant predictors of non-arrhythmic death., Conclusions: The MBS can identify suitable candidates for CRT-D among Japanese individuals.

Introduction: Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer. Less accessibility to the cSCC cell lines has limited analyses of this disease. Thus, we here aimed to establish novel cSCC cell lines from patient's cSCC lesions., Methods: Two novel cSCC cell lines (named KS-cSCC-1 and KS-cSCC-2) were established from an axillary lymph node metastasis of a Japanese female and an inguinal lymph node metastasis of a Japanese male. The characteristics of the established cell lines were assessed by in vitro analyses., Results: The cells were successfully maintained for more than 9 months, with a doubling time of 47.5 ± 1.11 h (KS-cSCC-1) and 39.2 ± 5.78 h (KS-cSCC-2). The cell lines exhibited constant growth, spheroid formation, and invasiveness. Short tandem repeat analyses and immunohistochemistry confirmed that both cell lines are identical to their original tumor. The KS-cSCC-1 cells were weakly positive for CK14 and strongly positive for CK10, while the KS-cSCC-2 showed opposite expression patterns. Chemosensitivity of the cell lines was further tested and the cells were sensitive to anticancer drugs which are used to treat cSCC., Conclusion: The KS-cSCC-1 and KS-cSCC-2 cell lines were promising resources for basic and preclinical research on cSCC to better define the tumor characteristics and treatment strategy of this cancer., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ito, Tanaka, Kaku-Ito, Tanegashima, Imajima, Ichiki and Nakahara.)

Staphylococcus aureus can cause outbreaks and becomes multi-drug resistant through gene mutations and acquiring resistance genes. However, why S. aureus easily adapts to hospital environments, promoting resistance and recurrent infections, remains unknown. Here we show that a specific S. aureus lineage evolved from a clone that expresses the accessory gene regulator (Agr) system to subclones that reversibly suppressed Agr and caused an outbreak in the hospital setting. S. aureus with flexible Agr regulation shows increased ability to acquire antibiotic-resistant plasmids, escape host immunity, and colonize mice. Bacteria with flexible Agr regulation shows altered cytosine genomic methylation, including the decreased 5mC methylation in transcriptional regulator genes (pcrA and rpsD), compared to strains with normal Agr expression patterns. In this work, we discover how altered genomic methylation promotes flexible Agr regulation which is associated with persistent pathogen colonization in the hospital environment., (© 2024. The Author(s).)

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic polyarthritis. It is well-established that helper T cells play crucial roles in the development and deterioration of RA. Recent studies also revealed the significant roles of regulatory T (Treg) cells in this context. Although Treg cells distributed in peripheral tissues exhibit various functions, the characteristics of synovial Treg cells remain unknown. In this study, we demonstrate that synovial Treg cells exacerbate synovial inflammation by reducing the number of immunoregulatory eosinophils through competitive consumption of IL-33. Synovial Treg cells expressed ST2 in a murine arthritis model, and surprisingly, Treg-specific ST2 knockout (ST2 ΔTreg ) mice exhibited attenuated arthritis. In ST2 ΔTreg mice, an increase in immunoregulatory synovial eosinophils was observed. Additionally, immunoregulatory eosinophils were found to express ST2, and ST2-expressing Treg cells controlled the abundance of immunoregulatory eosinophils, possibly by consuming IL-33. Our results highlight that a subset of synovial Treg cells possesses the machinery to worsen arthritis by suppressing eosinophils. In the future landscape where Treg cell-based therapies are employed for autoimmune diseases, it is important to comprehend the characteristics of disease-related Treg cells. Understanding these aspects is crucial for ensuring safer treatment modalities that do not inadvertently worsen the diseases., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The Drug Lymphocyte Stimulation Test (DLST), recognized for its safety as an allergy diagnostic modality, has been acknowledged for its utility in diagnosing drug-induced pathological conditions. However, reports elucidating DLST outcomes concerning local anesthetics are notably scarce., Materials and Methods: An exhaustive analysis was conducted on the DLST results pertaining to local anesthetics derived from 571 patients presenting with suspected allergies to these specific agents., Results: Remarkably, Stimulation Index (SI) > 1.8 was discerned in 11.4% and 7.8% of patients exhibiting hives or swelling subsequent to the administration of local anesthetics, surpassing the incidence observed in those experiencing post-injection discomfort. Additionally, SI > 3.0 was observed in 3 cases with lidocaine, 3 cases with prilocaine, and 1 case with mepivacaine. The distribution of SI exhibited a non-normal pattern for all three tested local anesthetics. Noteworthy is the case of a singular patient registering an SI of 1.84, who also yielded a positive challenge test, conclusively confirming an allergy to lidocaine., Conclusions: The DLST, holding promise as a potentially invaluable tool in identifying the causative factors behind adverse reactions to dental local anesthetics, lacks sufficient evidence to substantiate its efficacy definitively at present., Clinical Relevance: DLST, coupled with intradermal testing and challenge testing, may be elucidated in patients exhibiting indicators of suspected local anesthetic allergy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aim: Enfortumab Vedotin (EV) is a widely used antibody-drug conjugate for patients with advanced urothelial carcinoma (UC) who have previously been treated with platinum-based chemotherapy and immune checkpoint inhibitors. However, limited information is currently available on prognostic factors and risk classification. Therefore, the present study attempted to identify clinical factors that predict outcomes in patients with advanced UC treated with EV and to develop a novel risk classification model., Patients and Methods: We conducted a multicenter retrospective study including patients with advanced UC treated with EV. Oncological outcomes were assessed using progression-free survival (PFS) and overall survival (OS), and prognostic factors for PFS and OS were investigated. We then examined the usefulness of risk classification based on the prognostic factors identified., Results: Median PFS and OS were 7.1 and 16.3 months, respectively. High C-reactive protein levels (CRP level ≥0.5 mg/dl) and hypercalcemia (corrected calcium level >10.2 mg/dl) were identified as prognostic factors for PFS (p=0.012 and p=0.003, respectively) and OS (p=0.035 and p<0.001, respectively). We then divided patients into three risk groups: no prognostic factors group, one prognostic factor group, and two prognostic factors group. Significant differences were observed in PFS and OS among the three groups (p<0.001 and p<0.001, respectively) and c-indices were 0.766 for PFS and 0.800 for OS., Conclusion: The risk classification using CRP and hypercalcemia is useful for predicting the outcomes of patients with advanced UC treated with EV., Competing Interests: The Authors declare no conflicts of interest in relation to this study., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

Background: During the coronavirus disease (COVID-19) pandemic, Japan's health insurance system allowed continuous positive airway pressure (CPAP) telephone consultations to extend clinic visit intervals. This study aimed to determine whether 6-month CPAP adherence in the telemedicine (TM) group was inferior to that in the standard care group., Methods: Patients receiving long-term CPAP therapy for at least 6 months for obstructive sleep apnea (OSA) from two clinics in Japan were recruited between May and July 2020. The TM group consisted of patients who had not visited the clinic in person for 6 months, with physicians providing telephone consultations every 1-2 months. The standard care group included patients who visited the clinic monthly for physician consultation. In both groups, physicians reviewed CPAP usage data via telemonitoring. Patients were classified into three groups according to change in adherence: ≤ -5%, > -5 to <5%, and ≥5%. The primary outcome was the number of patients with worsened CPAP adherence (≤-5%)., Results: Of the 479 patients in the TM group and 146 in the standard care group, 120 were matched using propensity score 1:1 nearest neighbor matching and selected from both groups. Adherence worsened in 41 (34.2%) and 32 (26.7 %) patients in the TM and standard care groups, respectively. The TM group was not inferior to the standard care group in terms of the proportion of patients with worsened CPAP adherence (χ 2  = 1.81, df = 1, P = 0.178)., Conclusions: This study found no significant difference in the 6-month CPAP adherence between the TM and standard care groups., Competing Interests: Conflict of interest The Department of Sleep Medicine and Respiratory Care, led by Kazuo Chin and Yasuhiro Gon, is funded by donations to Nihon University from Philips Japan, ResMed Japan, Fukuda Denshi, and Fukuda Lifetech Tokyo; Kazuo Chin was supported by New Energy and Industrial Technology Development Organization (NEDO) under Grant Number Project JPNP23019, KYOTO Industrial Support Organization 21, Ministry of Education, Culture, Sports, Science and Technology in Japan under Grant-in-Aid for Scientific Research (23K07638), Japan Agency for Medical Research and Development (AMED) under Grant Numbers wm042501, Ministry of Health, Labor and Welfare of Japan Intractable Respiratory Diseases and Pulmonary Hypertension Research Group (20FC1027 and 23FC1031); Ryuji Furihata was supported by JSPS KAKENHI under Grant Number 20K07967, 22H03412; Kazuo Chin received consulting fees from Shionogi, Aculys Pharma and Eli Lilly; The other authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Augmented reality technologies provide transformative solutions in various surgical fields. Our research focuses on the use of an advanced augmented reality system that projects 3D holographic images directly into surgical footage, potentially improving the surgeon's orientation to the surgical field and lowering the cognitive load. We created a novel system that combines exoscopic surgical footage from the "ORBEYE" and displays both the surgical field and 3D holograms on a single screen. This setup enables surgeons to use the system without using head-mounted displays, instead viewing the integrated images on a 3D monitor. Thirteen surgeons and surgical assistants completed tasks with 2D and 3D graphical surgical guides. The NASA Task Load Index was used to assess mental, physical, and temporal demands. The use of 3D graphical surgical guides significantly improved performance metrics in cochlear implant surgeries by lowering mental, physical, temporal, and frustration levels. However, for Bonebridge implantation, the 2D graphical surgical guide performed better overall ( p = 0.045). Participants found the augmented reality system's video latency to be imperceptible, measuring 0.13 ± 0.01 s. This advanced augmented reality system significantly improves the efficiency and precision of cochlear implant surgeries by lowering cognitive load and improving spatial orientation.

Background/aim: Locally advanced squamous cell carcinoma of the head and neck (L/A SCCHN) is typically treated with surgery or chemoradiation therapy (CRT), whereas salvage surgery is considered for residual disease post-CRT. However, salvage surgery after radiation therapy presents challenges due to tissue fibrosis. Planned neck dissection (ND) combined with CRT, as well as positron emission tomography after CRT, have been proposed strategies, but no definitive consensus has been reached. Therefore, this study aimed to investigate the utility of "upfront ND" performed prior to CRT to enhance local control and reduce complications., Patients and Methods: We retrospectively reviewed 121 patients who underwent primary CRT for oropharyngeal, hypopharyngeal, or laryngeal cancer at Tokyo Medical University Hospital from January 2015 to September 2021. Patients without cervical lymph node metastasis or with unresectable nodes were excluded. All patients underwent pre-treatment imaging and staging. CRT consisted of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy. Selective ND or modified radical neck dissection was performed based on lymph node involvement., Results: Overall, 35 patients underwent upfront ND, whereas 54 did not. The upfront ND group exhibited significantly better 2-year locoregional recurrence-free survival than the group without upfront ND (93.7% vs. 71.0%). No significant differences were noted in adverse events between groups., Conclusion: The findings highlight upfront ND before CRT as a viable option for locally advanced head and neck cancer, particularly beneficial in cases with extranodal extension. This approach enhances local control and may reduce the need for salvage surgery, thus improving patient outcomes., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Nanoliposomal irinotecan with 5-fluorouracil and L-leucovorin (nal-IRI/FL) is the standard regimen for metastatic pancreatic cancer, but there are no reports on prediction of early discontinuation. In this study, we investigated predictive factors of early discontinuation of nal-IRI/FL., Patients and Methods: The study included 36 patients who received nal-IRI/FL at Wakayama Medical University Hospital between June 2021 and May 2022. Those with time-to-treatment failure (TTF) ≤28 days were defined as the early discontinuation group (group ED), and those with TTF >28 days were placed in the continuation group (group C). Laboratory data were collected just before and every 14 days after initiation of nal-IRI/FL treatment., Results: There were six patients (16.7%) in group ED and 30 patients (83.3%) in group C. The lymphocyte×albumin (LA) score before therapy was significantly lower in group ED (p=0.005). In receiver operating characteristic analysis, pre-treatment LA was the best predictor for early discontinuation, with a cutoff value of 4,142 (sensitivity: 1.00, specificity: 0.77, p=0.004). In group C, LA was significantly lower at 28 days before nal-IRI/FL treatment failure compared to the value before the start of therapy [median with range: 3,299 (1,478-6,994) vs. 4,304 (2,085-8,085), p=0.006]., Conclusion: The LA score is a useful marker for evaluating treatment continuity, and especially early discontinuation, of nal-IRI/FL in patients with pancreatic cancer., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Telomerase reverse transcriptase (TERT) gene aberration is detectable in >80% of cases with hepatocellular carcinoma (HCC). TERT reactivation is essential for cellular immortalization because it stabilizes telomere length, although the role of TERT in hepatocarcinogenesis remains unelucidated. To elucidate the significance of aberrant TERT expression in hepatocytes in inflammation-associated hepatocarcinogenesis, we generated Alb-Cre;TertTg mice, which overexpress TERT in the liver and examined their phenotype during chronic inflammation. Based on transcriptome data from the liver tissue of Alb-Cre;TertTg mice, we examined the role of TERT in hepatocarcinogenesis in vitro. We also evaluated the relationship between TERT and cell-cycle-related molecules, including p21, in HCC samples. The liver tumor development rate was increased by TERT overexpression during chronic inflammation, especially in the absence of p53 function. Gene set enrichment analysis of liver tissues revealed that gene sets related to TNF-NFκB signaling, cell cycle, and apoptosis were upregulated in Alb-Cre;TertTg liver. A luciferase reporter assay and immunoprecipitation revealed that TERT interacted with NFκB p65 and enhanced NFκB promoter activity. On the other hand, TERT formed protein complexes with p21, cyclin A2, and cyclin E and promoted ubiquitin-mediated degradation of p21, specifically in the G1 phase. In the clinical HCC samples, TERT was highly expressed but p21 was conversely downregulated, and TERT expression was associated with the upregulation of molecules related to the cell cycle. Taken together, the aberrant upregulation of TERT increased NFκB promoter activity and promoted cell cycle progression via p21 ubiquitination, leading to hepatocarcinogenesis. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Background: Steatotic liver disease (SLD) is associated with adverse cardiac events. Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a condition characterized by the abnormal accumulation of hepatic lipids that is closely linked to five metabolic disorders: overweight or obesity, impaired glucose regulation, hypertension, hypertriglyceridemia, and low high-density lipoprotein-cholesterol. This retrospective study aimed to stratify the risk of cardiac events in patients with MASLD., Methods: Patients diagnosed with MASLD through ultrasonography were evaluated. We implemented a machine learning-based approach using a survival classification and regression tree (CART) model to stratify patients based on age, and the number of risk scores was investigated as a predictor of adverse outcomes in the derivation cohort. The primary outcomes were major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease., Results: Among 2,962 patients (median age, 62 years; men, 53.5 %), the distribution of risk factors was as follows: one (10.8 %), two (28.5 %), three (33.0 %), four (19.9 %), and five (7.8 %). Over a median follow-up period of 6.8 years, 170 (5.7 %) patients experienced MACE. In the derivation cohort of 2,073 patients, the CART model identified age ≥60 years old and risk factors ≥4 as significant predictors of MACE. These findings were corroborated in a validation cohort of 889 patients. Patients meeting both criteria exhibited the highest risk of MACE (log-rank test, p < 0.001)., Conclusions: Patients aged ≥60 years old with risk factors ≥4 indicates at high risk of MACE in patients with MASLD. This risk stratification system provides a practical tool for identifying high-risk individuals in the MASLD population., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Aim: To detect immune-related adverse events (irAEs) early and treat them appropriately, our institute established an irAE-focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)-induced liver toxicity., Methods: To analyze the diagnosis and treatment of severe ICI-induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre-period, September 2014 to February 2019; post-period, March 2019 to March 2023)., Results: The median follow-up period was 392 days. Of the 1247 patients with advanced malignancies treated with ICIs, 66 developed severe ICI-induced liver toxicity (n = 22 and 44 in the pre- and post-periods, respectively). In the pre-period, hepatologist consultations were sought for 15/22 patients, whereas in the post-period, 42/44 patients were referred to and treated by hepatologists. The time from the onset of liver toxicity to the consultation was significantly shorter in the post-period than in the pre-period (mean 1.9 vs. 6.5 days, respectively; p = 0.012). The number of patients with a biopsy-confirmed diagnosis of ICI-induced liver toxicity was significantly higher in the post-period than in the pre-period (n = 22 vs. n = 3, respectively; p = 0.006). Finally, there were no cases of immune-related cholangitis in the pre-period, compared to five cases in the post-period., Conclusion: A hepatologist consultation system in an irAE-focused multidisciplinary toxicity team is useful for managing severe ICI-induced liver toxicity., (© 2024 Japan Society of Hepatology.)

Factors involved in the susceptibility of third-generation cephalosporins (3GCs) to bacteremia caused by Citrobacter freundii complex, Enterobacter cloacae complex, and Klebsiella aerogenes were investigated based on a case-case-control design. Antimicrobial therapy administered 30 days prior to bacteremia and hospitalization within 90 days were common risk factors for the 3GC susceptible and 3GC non-susceptible groups, while hospitalization from an institution or another hospital was a specific risk factor for the 3GC non-susceptible group. We also attempted to examine the factors affecting the clinical outcome of bacteremia. Hospitalization more than 14 days before the onset of bacteremia was an independent factor indicating poor clinical outcome. In contrast, the implementation of source control was an independent predictor of successful treatment. Although a longer hospital stay before the onset of bacteremia was associated with worse clinical outcomes, implementation of source control may have contributed to improved treatment outcomes for bacteremia.

Background: Clinical findings and postoperative follow-up data on remnant gastric cancer (RGC) are limited due to its rarity. Additionally, the preoperative staging, radical surgery, and managing recurrence in RGC present significant clinical challenges., Methods: We analyzed the clinicopathological findings, adjuvant chemotherapy, and patterns of postoperative recurrence of 313 consecutive patients who underwent curative surgery for RGC at 17 Japanese institutions. This study investigated the optimal management of RGC and the impact of adjuvant chemotherapy (AC) on recurrence-free survival (RFS)., Results: Pathological stages I, II, and III were observed in 55.9% (N = 175), 24.9% (N = 78), and 19.2% (N = 60) of the patients, respectively. The overall concordance rate between clinical and pathological T staging was 58.3%, with a clinical T4 sensitivity of 41.4% for diagnosing pathological T4. During the median follow-up period of 4.6 years, disease recurrence occurred in 24.3% of patients. Most recurrences (over 80%) occurred within 2.5 years, and 96.1% within 5 years after RGC surgery. Peritoneal recurrence was the most common in patients with advanced RGC, accounting for 14.1% in stage II and 28.3% in stage III. Multivariable regression analysis showed that AC was significantly associated with a longer RFS, with a hazard ratio of 0.45 (95% confidence interval: 0.26-0.76)., Conclusions: Our study underscores the importance of early detection, accurate preoperative staging, and postoperative surveillance in managing advanced RGC cases. Despite some limitations, our findings indicate that AC may provide survival benefits comparable to those seen in primary gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Venetoclax was approved for relapsed/refractory chronic lymphocytic leukemia (R/R CLL) and small lymphocytic leukemia (SLL) in Japan in September 2019; however, clinical data in Japanese patients are limited. This all-case post-marketing surveillance assessed efficacy and safety in Japanese patients with R/R CLL/SLL who started venetoclax treatment between November 2019 and August 2020. Overall, the safety and efficacy analysis sets included 129 and 114 patients, respectively. The overall response rate (ORR) was 57.0%; ORRs were higher in patients with versus without concomitant rituximab (65.4% vs. 54.7%), and in patients with 1 versus ≥ 2 prior lines of therapies (72.5% vs. 44.4%). Adverse events (AEs) were reported in 66.7% of patients (86/129); the most common AEs were neutrophil count decreased (22.5%), white blood cell count decreased (7.8%), and tumor lysis syndrome (TLS; 6.2%). AEs of special interest (TLS, myelosuppression, and infection) were manageable in clinical practice in Japan. Venetoclax is efficacious and safe for R/R CLL/SLL patients in the real-world setting in Japan. ClinicalTrials.gov ID: NCT04198415., (© 2024. The Author(s).)

Background: The increasing trend of cervical cancer in women in their 20s in Japan is largely attributable to the low rate of cervical cancer screening. This study aimed to assess the usefulness of human papillomavirus (HPV) self-sampling among 24-year-old Japanese women who had never previously been screened for cervical cancer during the coronavirus disease (COVID-19) pandemic., Methods: In August 2021, consenting eligible women received HPV self-sampling kits. An Evalyn brush was used for self-sampling, and a Cobas 4800 PCR-based HPV DNA test was used to detect high-risk HPV genotypes. We analyzed the return rates of self-sampling kits and conducted a survey on the acceptability of the self-sampling method., Results: Of the total 1997 eligible women, 13.4% (268/1997) agreed to participate. The return rate of the kits was 72.4% (194/268), corresponding to 9.7% of the eligible population. Among the participants who returned the kits, 14.9% (29/194) tested positive for HPV, and 41.4% (12/29) of these underwent subsequent cytological testing. The questionnaire results indicated that 57.8% of participants reported no pain during self-sampling, and 72.9% expressed a willingness to continue using the self-sampling method in the future., Conclusion: This study demonstrated that opt-in HPV self-sampling among 24-year-old women who had never been screened for cervical cancer had a favorable kit return rate and was well accepted by the participants, especially during the COVID-19 pandemic. However, the follow-up cytology test rates were low, highlighting the need for improved post-screening management.

Background: In hepatocellular carcinoma (HCC), postoperative recurrence remains high. This study aimed to evaluate the recurrence patterns and prognosis of HCC after curative hepatectomy., Methods: Among 352 patients with primary HCC who underwent initial hepatectomy between January 2002 and December 2022, 151 with recurrence were assessed for the relationship between recurrence pattern and prognosis., Results: The early recurrence group (within 6 months postoperatively; n = 38) had significantly higher serum alpha-fetoprotein (p = 0.002), des-γ-carboxyprothrombin (DCP; p = 0.004) levels and Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.001), larger tumor size (p < 0.001), higher incidence of multiple tumors (p = 0.002) and lower overall survival (OS) (p < 0.001) than the late recurrence group (> 6 months postoperatively; n = 113). The tumor size (p = 0.013) and BCLC stage (p = 0.001) were independent risk factors for early recurrence within 6 months in multivariate analysis. The multiple recurrence group (intrahepatic multinodular recurrence or distant metastasis; n = 89) had significantly lower prognostic nutritional index (p = 0.026), larger tumor size (p = 0.017), lower incidence of liver cirrhosis (p = 0.03) than the single recurrence group (single nodule recurrence; n = 62). The multiple recurrence group, especially patients with ≥ three intrahepatic nodules and distant metastases, had lower postoperative OS (p < 0.001) and shorter time to recurrence (p < 0.001) than the single recurrence group. When the patients were classified into three groups: late recurrence with one or two tumors (Group A; n = 74), early recurrence or three or more tumors or distant metastasis (Group B; n = 54), and early recurrence with three or more tumors or distant metastasis (Group C; n = 23), OS was significantly lower in Groups B and C than Group A (p < 0.001)., Conclusions: Patients with early recurrence within 6 months after surgery and three or more recurrence nodule or distant metastasis exhibited poor prognosis after initial recurrence, and they should be carefully followed up., (© 2024. The Author(s).)

Kamiue M, Tsubahara A, Ito T, Koike Y. Effects of repetitive peripheral magnetic stimulation on knee joint extensor strength in older persons receiving day services. Jpn J Compr Rehabil Sci 2024; 15: 49-57., Objective: To verify the effects of repetitive peripheral magnetic stimulation (rPMS) on knee joint extensor strength and motor ability in older adults receiving day services., Methods: Thirty Hz rPMS using Talent Pro ® was applied to the bilateral vastus lateralis, vastus medialis, and rectus femoris of 12 older persons (mean age 83.8 ± 4.5 years) attending a day service center and receiving functional training by a physical therapist. The intervention was performed for 20 minutes per day, three times per week, for a total of 4 weeks. Evaluations before and after the intervention included maximum voluntary contraction (MVC), knee extensor torque induced by rPMS (rPMS-induced torque), pain (visual analog scale: VAS), thigh circumference, comfortable 5-m walking time, 30-second chair-stand test (CS-30), Timed-Up-and-Go Test (TUG), and Functional Reach Test (FRT). MVC and rPMS-induced torque were measured using the μ-Tas F-1 ® ., Results: MVC significantly increased in both lower limbs after the intervention (right/left: 72.4 ± 23.5 Nm/72.9 ± 23.0 Nm) compared with immediately before the intervention (right/left: 59.9 ± 17.2 Nm/64.5 ± 21.0 Nm). No significant changes were observed in MVC between one month before the intervention and immediately before the start of the intervention, and between the end of the intervention and one month after the end of the intervention. rPMS-induced torque, TUG, and CS-30 improved significantly after the intervention compared with immediately before the intervention., Conclusion: Intervention using rPMS increases MVC- and rPMS-induced torque and improves motor ability in older adults. Because rPMS is a simple means of increasing muscle strength, it is expected to be widely used in the future., (©2024 Kaifukuki Rehabilitation Ward Association.)

Initial studies on the immunogenicity of SARS-CoV-2 (CoV-2) S glycoprotein ("spike") as a protein subunit vaccine suggested sub-optimal efficacy in mammals. Although protein engineering efforts have produced CoV-2 spike protein sequences with greatly improved immunogenicity, additional strategies for improving the immunogenicity of CoV-2 protein subunit vaccines are scaffolding and the use of adjuvants. Comparisons of the effectiveness of engineered protein-only and engineered protein-nanoparticles vaccines have been rare. To explore this knowledge gap, we inoculated mice with two doses of either sequence-optimized trimeric spike protein or one of several sequence-optimized spike nanoparticles. We measured their immune response up to two months after the first dose. We also measured the immune response and protection against live virus in hamsters inoculated with either sequence-optimized trimeric spike protein or a liposome-based sequence-optimized spike nanoparticle. We found that in the presence of adjuvant, the antibody and neutralization titers elicited by spike-nanoparticles were not significantly greater than those elicited by spike-only in mice, even at doses as low as 0.1 µg/animal. Hamsters vaccinated with spike-only or spike-nanoparticles were equally protected from live virus one month after their first inoculation. These results suggest that sequence-optimized protein subunit vaccines in the form of individual prefusion-stabilized trimers can be as effective in improving immunogenicity as scaffolded forms., (© 2024. The Author(s).)

Atopic dermatitis (AD), a prevalent Th2-dominant skin disease, involves complex genetic and environmental factors, including mutations in the Filaggrin gene and dysbiosis of skin microbiota characterized by an increased abundance of Staphylococcus aureus. Our recent findings emphasize the pivotal role of the skin barrier's integrity and microbial composition in infantile AD and allergic diseases. Early skin dysbiosis predisposes infants to AD, suggesting targeted skincare practices as a preventive strategy. The effects of skincare interventions, particularly the application of moisturizers with the appropriate molar concentration of ceramides, cholesterol, and fatty acids, play a crucial role in restoring the skin barrier. Notably, our study revealed that appropriate skincare can reduce Streptococcus abundance while supporting Cutibacterium acnes presence, thus directly linking skincare practices to microbial modulation in neonatal skin. Despite the mixed outcomes of previous Randomized Controlled Trials on the efficacy of moisturizers in AD prevention, our research points to the potential of skincare intervention as a primary preventive method against AD by minimizing the impact of genetic and environmental factors. Furthermore, our research supports the notion that early aggressive management of eczema may reduce the incidence of food allergies, highlighting the necessity for multifaceted prevention strategies that address both the skin barrier and immune sensitization. By focusing on repairing the skin barrier and adjusting the skin's microbiome from birth, we propose a novel perspective on preventing infantile AD and allergic diseases, opening new avenues for future studies, and practices in allergy prevention., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In Japan, pharmaceutical approval for the use of the da Vinci SP (dV SP) Surgical System in colorectal cancer surgery was obtained in September 2022. This system has an operating arm with three instruments and one scope to be manipulated through a single incision in colorectal cancer surgery. An 88-year-old female presented to our hospital with melena and was diagnosed with cStage IIa descending colon cancer (cT3N0M0). The patient underwent left hemicolectomy with the dV SP using an Access Port kit. The Access Port kit was inserted into a 3-cm vertical skin incision at the umbilicus. With only this surgical wound, mobilization from the rectum to the colon, and lymph node dissection were performed. Herein, we report the world's first descending colon cancer resection with the dV SP using an Access Port kit., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

Purpose: Orofacial somatosensory inputs play an important role in speech motor control and speech learning. Since receiving specific auditory-somatosensory inputs during speech perceptual training alters speech perception, similar perceptual training could also alter speech production. We examined whether the production performance was changed by perceptual training with orofacial somatosensory inputs., Method: We focused on the French vowels /e/ and /ø/, contrasted in their articulation by horizontal gestures. Perceptual training consisted of a vowel identification task contrasting /e/ and /ø/. Along with training, for the first group of participants, somatosensory stimulation was applied as facial skin stretch in backward direction. We recorded the target vowels uttered by the participants before and after the perceptual training and compared their F1, F2, and F3 formants. We also tested a control group with no somatosensory stimulation and another somatosensory group with a different vowel continuum (/e/-/i/) for perceptual training., Results: Perceptual training with somatosensory stimulation induced changes in F2 and F3 in the produced vowel sounds. F2 decreased consistently in the two somatosensory groups. F3 increased following the /e/-/ø/ training and decreased following the /e/-/i/ training. F2 change was significantly correlated with the perceptual shift between the first and second half of the training phase in the somatosensory group with the /e/-/ø/ training, but not with the /e/-/i/ training. The control group displayed no effect on F2 and F3, and just a tendency of F1 increase., Conclusion: The results suggest that somatosensory inputs associated to speech sound inputs can play a role in speech training and learning in both production and perception.

Rats were the first mammals to be domesticated for scientific research, and abundant physiological data are available on them. Rats are expected to continue to play an important role as experimental animals, especially with advancements such as CRISPR/Cas9 technology. Environmental enrichment aims to promote species-specific behaviors and psychological well-being. In the present study, we designed a double-decker (DD) cage, which utilizes two stacked plastic cages for rat enrichment, and investigated the influence of housing in the DD cage on rat mating behavior. The results indicated that mount frequency, total mount counts, and total ejaculation latency were significantly lower in the DD cages than in the single-decker (SD) cages. Notably, in the DD cages, the body weight loss of male rats after mating behavior was lower than that observed in the SD cage. Water consumption per day during mating behavior was also significantly lower in the DD cages, although no significant differences were observed in daily food intake during mating behavior. In addition, reproductive performance, including pregnancy rate and birth rate, did not change in the DD cages. In summary, our study demonstrated that DD cages reduce mount frequency and ejaculation latency during rat mating, resulting in decreased water consumption and weight loss in male rats. Therefore, housing in DD cages may serve as a beneficial enrichment for rats.