Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Liquid–liquid phase separation by caged coacervating peptides10464ENAkinariBandoDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMizukiKitamatsuDepartment of Applied Chemistry, Kindai UniversityYuukiKanazakiDepartment of Applied Chemistry, Kindai UniversityRikaTojoDepartment of Applied Chemistry, Kindai UniversityKazunoriWatanabeDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityLiquid–liquid phase separation is an important biomolecular process in the formation of membraneless intracellular organelles that has inspired the development of artificial droplet systems. We developed caged coacervating peptides (CCPs) based on a histidine-rich squid beak protein sequence. The peptides were caged with a photodeprotectable (7-diethylaminocoumarin-4-yl)methoxycarbonyl group. The CCPs formed coacervates in the caged state and were partially dispersed upon blue-light irradiation. Photo-uncaging occurred rapidly, inducing coacervate dispersion. A mutant CCP with reduced π–π interactions exhibited efficient photo-dependent disassembly and enabled the encapsulation and release of a fluorescently labeled adenosine 5′-triphosphate (Bodipy-ATP) upon irradiation. These CCPs offer an efficient light-controlled approach for biomolecular encapsulation within coacervates and targeted drug delivery.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1472-68312612026Evaluation of contact-active antibacterial properties of cetylpyridinium chloride–graphene oxide coatings on dental restorative and titanium surfaces: an in vitro study558ENKeisukeOkuboDepartment of Periodontics and Endodontics, Field of Medical Development, Okayama UniversityGenKanoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasatoKomodaResearch Institute for Interdisciplinary Science, Okayama UniversityHideyukiKamataGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinNakamuraDepartment of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiShinoda-ItoDepartment of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOmoriDepartment of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYutaNishinaResearch Institute for Interdisciplinary Science, Okayama UniversityShogoTakashibaDepartment of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityObjective Biofilm formation on dental restorative materials and implant surfaces plays a central role in the development of dental caries, periodontal disease, and peri-implantitis. Durable antimicrobial surface treatments that inhibit bacterial adhesion and biofilm formation remain a significant unmet need in restorative and implant dentistry. Therefore, this study aimed to develop a composite coating combining cetylpyridinium chloride and graphene oxide, and to evaluate its durable antibacterial surface modification under in vitro conditions.<br>
Methods A composite coating consisting of cetylpyridinium chloride and graphene oxide was prepared and applied to composite resin and titanium surfaces. Antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis was evaluated using adenosine triphosphate assays and fluorescence-based live/dead staining. Coating retention after washing and air-drying was assessed by optical microscopy and Raman spectroscopy.<br>
Results Cetylpyridinium chloride-graphene oxide-coated surfaces showed a significant reduction in bacterial viability compared with phosphate-buffered saline, ethanol, and cetylpyridinium chloride-only controls. Antibacterial effects were maintained after rinsing and air-drying on both composite resin and titanium surfaces. Raman spectroscopy confirmed the persistence of characteristic graphene oxide bands after washing, indicating stable retention of the coating on the material surfaces.<br>
Conclusions Cetylpyridinium chloride–graphene oxide coatings demonstrate sustained surface-associated antibacterial activity against key cariogenic and periodontal pathogens and remain stably adhered to common dental restorative and implant materials after washing. These findings suggest that cetylpyridinium chloride–graphene oxide coatings may serve as a durable contact-active surface modification strategy to reduce biofilm formation associated with dental caries and peri-implantitis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0971-5894|0974-04302026Suppression of salt-enhanced apoplastic flow by salicylic acid in riceENMd. Asadulla AlGalibGraduate School of Environmental and Life Science, Okayama UniversityMaoxiangZhaoGraduate School of Environmental and Life Science, Okayama UniversityToshiyukiNakamuraGraduate School of Environmental and Life Science, Okayama UniversityYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityYoshihikoHiraiGraduate School of Environmental and Life Science, Okayama UniversityYoshitakaNakashimaGraduate School of Environmental and Life Science, Okayama UniversityShintaroMunemasaGraduate School of Environmental and Life Science, Okayama UniversityIzumi C.MoriInstitute of Plant Science and Resources, Okayama UniversityYoshiyukiMurataGraduate School of Environmental and Life Science, Okayama UniversitySalinity enhances apoplastic flow, resulting in an increment of Na+ uptake and a lower K+/Na+ ratio. Salicylic acid (SA) plays an important role in improving salinity tolerance in plants. The effect of exogenous SA on apoplastic flow in salt-treated rice seedlings was studied using an apoplastic tracer, 8-hydroxy-1,3,6-pyrenetrisulphonic acid (PTS) in light. Application of NaCl at 25 mM to the hydroponic solution significantly increased PTS uptake, while 25 mM NaCl did not affect seedling growth. Application of 25 mM NaNO3 increased PTS uptake to the same degree. Salinity significantly increased sodium (Na+) content but had no significant effect on potassium (K+) content, resulting in a lower K+/Na+ ratio. The application of SA at 0.05 mM and 0.1 mM to the hydroponic solution reduced Na-enhanced PTS uptake. Salicylic acid at 0.05 mM and 0.1 mM significantly reduced Na+ content and slightly increased K+ content in the shoots of rice seedlings, resulting in a higher K+/Na+ ratio. However, SA at up to 0.1 mM did not increase SA contents in shoots under salt stress. These results suggest that exogenous SA reduces Na+ uptake by suppressing Na+-enhanced apoplastic flow in rice seedlings. These findings provide insight into modulation of Na+ transport pathways from roots to shoots by SA and may allow us to utilize brackish water for rice cultivation and to improve salt-tolerant rice through suppression of salt-enhanced apoplastic flow by chemicals such as salicylic acid.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2662-4435712026Stability and distribution of dense hydrous magnesium silicates in the mantle transition zone under low water activity conditions265ENYunkeSongKey Laboratory of High-temperature and High-pressure Study of the Earth’s Interior, Institute of Geochemistry, Chinese Academy of SciencesXinzhuanGuoState Key Laboratory of Critical Mineral Research and Exploration, Institute of Geochemistry, Chinese Academy of SciencesKuanZhaiKey Laboratory of High-temperature and High-pressure Study of the Earth’s Interior, Institute of Geochemistry, Chinese Academy of SciencesWeiGuoState Key Laboratory of Geomicrobiology and Environmental Changes, School of Earth Sciences, China University of Geosciences (Wuhan)TakashiYoshinoInstitute for Planetary Materials, Okayama UniversityWater plays a central role in controlling the physical and chemical properties of Earth’s deep interior. It remains uncertain how water is stored in subducting slabs within the mantle transition zone, between depths of about 410 and 660 kilometers, and whether dense hydrous magnesium silicates act as major water carriers to greater depths. Here we report high-pressure and high-temperature laboratory experiments on the Mg-Si-H system at pressures of 16 and 21.5 GPa and a temperature of 1400 K to evaluate hydrous phase stability under transition zone conditions. We find that when bulk water content is below 1.22 wt%, H2O is predominantly incorporated into wadsleyite and ringwoodite rather than forming dense hydrous magnesium silicates. Because estimated water contents in subducted oceanic slabs are typically lower than one weight percent, formation of these silicates is unlikely, suggesting that the mantle transition zone may restrict large scale water transport into the lower mantle.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2662-4443612025From localized 4f electrons to anisotropic exchange interactions in ferromagnetic CeRh6Ge4269ENShoichiroItokazuDepartment of Physics, Okayama UniversityAkimitsuKirikoshiResearch Institute for Interdisciplinary Science, Okayama UniversityHarald O.JeschkeResearch Institute for Interdisciplinary Science, Okayama UniversityJunyaOtsukiResearch Institute for Interdisciplinary Science, Okayama UniversityCeRh6Ge4 is a cerium-based ferromagnetic material exhibiting a quantum critical behavior under pressure. We derive effective exchange interactions, using the framework of density functional theory combined with dynamical mean-field theory. Our results reveal that the nearest-neighbor ferromagnetic interaction along the c axis is isotropic in spin space, leading to a formation of spin chains. On the other hand, the inter-chain coupling is highly anisotropic: The in-plane moment weakly interacts ferromagnetically in the a–b plane to stabilize the ferromagnetic state, whereas the z-component couples antiferromagnetically, contributing to its destabilization. The magnetic anisotropy of the interchain interactions as well as of the local 4f wavefunctions characterizes the magnetic properties underlying the ferromagnetic transition and the quantum critical behavior in CeRh6Ge4.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-08517532026A real-world comparison of nivolumab plus cabozantinib and pembrolizumab plus lenvatinib focusing on safety outcomes in metastatic renal cell carcinoma: results from the JK-FOOT consortium84ENTakafumiYanagisawaDepartment of Urology, The Jikei University School of MedicineKeiichiroMoriDepartment of Urology, The Jikei University School of MedicineTatsushiKawadaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaSatoshiKatayamaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaTakuyaTsujinoDepartment of Urology, Osaka Medical and Pharmaceutical UniversityRyoichiMaenosonoDepartment of Urology, Osaka Medical and Pharmaceutical UniversityShingoToyodaDepartment of Urology, Faculty of Medicine, Kindai UniversityTakuhisaNukayaDepartment of Urology, Fujita-Health University School of MedicineHirofumiMorinakaDepartment of Urology, Kawasaki Medical SchoolKeitaTamuraDepartment of Urology, Hamamatsu Medical UniversityWataruFukuokayaDepartment of Urology, The Jikei University School of MedicineFumihikoUrabeDepartment of Urology, The Jikei University School of MedicineMasayaMurakamiDepartment of Urology, The Jikei University School of MedicineKensukeBekkuDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKiyoshiTakaharaDepartment of Urology, Fujita-Health University School of MedicineKazutoshiFujitaDepartment of Urology, Faculty of Medicine, Kindai UniversityHaruhitoAzumaDepartment of Urology, Osaka Medical and Pharmaceutical UniversityMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTeruoInamotoDepartment of Urology, Hamamatsu Medical UniversityKazumasaKomuraDepartment of Urology, Kawasaki Medical SchoolTakahiroKimuraDepartment of Urology, The Jikei University School of MedicinePurpose Immune checkpoint inhibitor (ICI)-based combination therapy is a standard first-line treatment for metastatic renal cell carcinoma (mRCC), with combinations such as nivolumab plus cabozantinib (Nivo + Cabo) and pembrolizumab plus lenvatinib (Pem + Len) demonstrating favorable oncologic outcomes. However, no direct comparisons between these two regimens have been conducted. This study aimed to compare the safety and oncologic outcomes of Nivo + Cabo and Pem + Len in patients with mRCC.<br>
Methods This retrospective study included 185 patients with mRCC treated with Nivo + Cabo (n = 81) or Pem + Len (n = 104) between January 2018 and June 2025 across multiple institutions. The primary outcome was a comparison of treatment-related adverse events (TrAEs). Oncologic outcomes, including objective response rate (ORR), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared using one-to-one propensity score matching.<br>
Results Any-grade TrAEs occurred in 90% of patients in the Nivo + Cabo group and 92% in the Pem + Len group (p = 0.6). Severe TrAEs (grade ≥ 3) were more frequent in the Pem + Len group (44%) than in the Nivo + Cabo group (30%, p = 0.048). Tyrosine kinase inhibitor dose reduction and treatment discontinuation rates were similar between groups. In the matched cohort (Nivo + Cabo: n = 74; Pem + Len: n = 74), ORRs were comparable (66% vs. 71%, p = 0.6). With a median follow-up of 17 months, no significant differences were observed in PFS (p = 0.4), CSS (p = 0.9), or OS (p = 0.5).<br>
Conclusions Nivo + Cabo and Pem + Len demonstrated similar oncologic efficacy as first-line treatments for mRCC. However, Pem + Len was associated with more severe TrAEs. Careful toxicity management and shared decision-making are essential when selecting ICI-based combinations.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2192-44491512026A case of tubulointerstitial nephritis with infiltration of neutrophils and interleukin-17-positive cells associated with Behçet’s disease35ENNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKeikoTanakaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesNatsukiKubotaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTakayukiKatsuyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiTanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesBehçet’s disease (BD) is a non-infectious inflammatory condition characterized by neutrophilic infiltration. In addition to primary symptoms, including oral and genital ulcers, ocular involvement, and skin lesions, BD can also affect various organs. However, renal involvement, particularly in tubulointerstitial nephritis, has rarely been described. Herein, a rare case of acute tubulointerstitial nephritis in a patient clinically diagnosed with BD is reported. The renal lesion presented with other symptoms of BD and fever, and was considered to be BD-related due to the presence of neutrophilic infiltration and its responsiveness to BD-directed therapy. Alterations in T-helper (Th) 1, Th2, and Th17 cytokine profiles are associated with BD activity. Interleukin (IL)-17 plays a central role in neutrophil activation, and recent studies have demonstrated a strong correlation between IL-17A levels and BD activity. In the present case, elevated serum IL-17A levels and infiltration of IL-17A-positive cells into the renal tissue reflected an active phase of BD and a BD-associated renal lesion.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Tribolium castaneum with longer duration of tonic immobility have more variations corresponding to the human Parkinson’s disease genomic region8840ENKeisukeTanakaNODAI Genome Research Center, Tokyo University of AgricultureKenSasakiGraduate School of Agriculture, Tamagawa UniversityShunsukeYajimaNODAI Genome Research Center, Tokyo University of AgricultureTakahisaMiyatakeFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityParkinson’s disease (PD) is a common neurodegenerative syndrome characterized by the loss of dopaminergic neurons and is also a progressive neurodegenerative disorder that is characterized by dopamine deficiency. We established strains artificially selected for longer and shorter durations of tonic immobility, an antipredator behavior that has received much attention recently, in the red flour beetle, Tribolium castaneum, a model insect species for molecular analyses different from Drosophila melanogaster. Previous studies have shown that the long strains (L-strain) have significantly lower levels of dopamine expression in the brain than the short strains (S-strain) and that they have an abnormal pattern of locomotor activity. Furthermore, previous studies have shown that administering dopamine to L-strain beetles reduces the duration of tonic immobility. Transcriptome analysis of brain and thorax of the L- and S-strains also showed differences in mRNA expression of genes involved in dopamine synthesis and tyrosine metabolism. These results indicate that the phenotype and molecular basis of the L-strain are similar to those of Parkinson’s syndrome symptoms. In order to establish a link between T. castaneum and PD, we compared the DNA sequences of the L- and S-strains to human genes affecting dopaminergic pathways. The DNA comparison revealed many mutated regions in these genes in the L-strain. We discuss the relationship between dopaminergic pathway genes and PD-like phenotypes across humans, Drosophila, and the red flour beetle.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1046-13104562026Adolescent screen use in the pre-internet era and subsequent health and well-being: an outcome-wide longitudinal study657ENPedro Antoniode la Rosa Fernández-PachecoYouth in Transition, Institute for Culture and Society, Universidad de NavarraRenaeWilkinsonHuman Flourishing Program, Institute for Quantitative Social Science, Harvard UniversityRichard G.CowdenHuman Flourishing Program, Institute for Quantitative Social Science, Harvard UniversityYingChenHuman Flourishing Program, Institute for Quantitative Social Science, Harvard UniversityBrendanCaseHuman Flourishing Program, Institute for Quantitative Social Science, Harvard UniversityEtsujiSuzukiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTyler J.VanderWeeleDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThis study used data from the National Longitudinal Study of Adolescent to Adult Health (Add Health, N = 11,054) to assess whether increases in screen-based leisure during adolescence (Wave II, from 1996) predicted adult well-being (Wave IV, from 2008-09), adjusting for a wide range of covariates (Wave I, from 1995). Using an outcome-wide analytic approach, we examined associations between screen time and 38 adult outcomes, adjusting for prior screen time, values of most outcomes, and confounders. Most associations were null. Modest evidence was found for links between screen time (continuous) and reduced sense of control, illicit drug use, and allostatic load. High screen time (14 h/week) or more also showed weak associations with lower depression and preventive care use. Because the data predate widespread internet use, the findings help establish a baseline for the long-term effects of non-internet screen activities, which appeared to behave had limited impact on adult health and well-being.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2397-46481112026Band-selective plasmonic polaron in thermoelectric semimetal Ta2PdSe6 with ultra-high power factor23ENDaikiOotsukiResearch Institute for Interdisciplinary Science, Okayama UniversityAkitoshiNakanoPresent address: Department of Applied Physics, Nagoya UniversityUraraMaruokaPresent address: Department of Applied Physics, Nagoya UniversityTakumiHasegawaGraduate School of Advanced Science and Engineering, Hiroshima UniversityMasashiAritaResearch Institute for Synchrotron Radiation Science, Hiroshima UniversityMihoKitamuraPresent address: NanoTerasu Center, National Institutes for Quantum Science and Technology (QST)KojiHoribaPresent address: NanoTerasu Center, National Institutes for Quantum Science and Technology (QST)TeppeiYoshidaGraduate School of Human and Environmental Studies, Kyoto UniversityIchiroTerasakiPresent address: Department of Applied Physics, Nagoya UniversityWe report the electronic structure of the thermoelectric semimetal Ta2PdSe6 with a large thermoelectric power factor and giant Peltier conductivity by means of angle-resolved photoemission spectroscopy (ARPES). The ARPES spectra reveal the coexistence of a sharp hole band with a light electron mass and a broad electron band with a relatively heavy electron mass, which originate from different quasi-one-dimensional (Q1D) chains in Ta2PdSe6. Moreover, the electron band around the Brillouin-zone (BZ) boundary shows a replica structure with respect to the energy originating from plasmonic polarons due to electron-plasmon interactions. The different scattering effects and interactions in each atomic chain lead to asymmetric transport lifetimes of carriers: a large Seebeck coefficient can be realized even in a semimetal. Our findings pave the way for exploring the thermoelectric materials in previously overlooked semimetals and provide a new platform for low-temperature thermoelectric physics, which has been challenging with semiconductors.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1478-811X2412026MMP-3 cleavage of Lamin A induces pro-migratory nuclear deformity, nucleophagy, and their autophagic secretion with extracellular vesicles in metastatic cancer146ENTakanoriEguchiDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityEman A.TahaDepartment of Biochemistry, Faculty of Science, Ain Shams UniversityKeisukeNakanoDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityVikasTiwariCouncil of Scientific & Industrial Research-Indian Institute of Toxicological ResearchKatsukiTakebeDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohiroInoueDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityLiziXingDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChiharuSogawaDepartment of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of TechnologyKuniakiOkamotoDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityStuart K.CalderwoodDivision of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolMatrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that cleave a plethora of substrates, including components of the extracellular matrix and cell-surface-associated proteins, as well as intracellular targets. MMPs have also been found in extracellular vesicles (EVs), such as exosomes. MMP-3 promotes tumor growth, epithelial-to-mesenchymal transition, genome instability, migration, invasion, and metastasis of cancer cells, and nuclear MMP-3 controls gene transcription. Intranuclear proteolysis by MMPs may significantly alter cancer progression. However, the nuclear substrates of MMP-3 have not been well investigated. In this study, we performed proteomic analyses to identify the nuclear substrates and EV proteins regulated by MMP-3. While rabidly metastatic colon cancer (LuM1) three-dimensionally cultured tumoroids secreted EVs containing 30 protein types, including Lamin A (LMNA), MMP-3, fibronectin (FN1), HSPA8 (Hsc70), β-actin (ACTB), and vimentin (VIM), CRISPR/Cas9-based knockout of MMP-3 reduced the secretion of these proteins in EVs. Notably, EV-bound cleaved Lamin secretion was confirmed by immunoelectron microscopy. Also, MMP-3 formed proteolytic dimers via its hemopexin-like repeat domains in nuclei. Many nuclear MMP-3-binding proteins, including Lamin A/C, histones, topoisomerases, and hnRNPs, were screened by co-immunoprecipitation followed by proteomics. Proteolytic MMP-3 overexpression generated a C-terminal 30-kDa fragment of Lamin A, whose cleavage site was defined via structural analysis. MMP-3 digestion of Lamin A induced nuclear deformity (atypia) required for cell migration in confined space. The cleaved Lamin A and MMP-3 were transported with autophagosomes (LC3B+), nucleophagosomes, and amphisomes (CD63 + LC3B+) and co-secreted with EVs. Proteolytic MMP-3 also induced nuclear speckles of Lamin A, suggesting their roles in transcription and splicing. Clinical analysis revealed that high expressions of MMP3 and LMNA were significantly seen in head and neck squamous cell carcinoma (HNSC) than in the other 16 cancer types, and predicted poor prognosis of patients suffering from HNSC, pancreatic, rectum and lung adenocarcinomas at specific stages. Immunohistochemistry revealed that nuclear MMP-3 and cleaved Lamin were significantly higher expressed in stage IV metastatic HNSC cases than in stage I non-metastatic cases. Taken together, MMP3-cleavage of Lamin A induces nuclear deformity, nucleophagy, and their autophagic co-secretion with EVs in metastatic cancer. Also, high expression of MMP-3 and secretion of Lamin A can predict poor prognosis in multiple cancer types at specific stages.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2055-02941212026Association between the incidence of infusion-related reactions by obinutuzumab and the dose of corticosteroid as premedication: a multicenter retrospective cohort study27ENTatsuyaOhtsuboDepartment of Pharmacy, Japanese Red Cross Kyoto Daini HospitalKazuhiroYamamotoDepartment of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySaoriMatumotoDepartment of Pharmacy, Japanese Red Cross Osaka HospitalKaoriItoFaculty of Pharmacy, Meijo UniversityYuzukaSasaDepartment of Pharmacy, Kindai University HospitalKosukeTomishimaDepartment of Pharmacy, Japanese Red Cross Kyoto Daiichi HospitalSatoshiDoteDepartment of Pharmacy, Kyoto-Katsura HospitalKatuyaMakiharaDepartment of Pharmacy, Yodogawa Christian HospitalYoshinoriWakasugiDepartment of Pharmacy, Shiga University of Medical Science HospitalTsutomuMitsuieDepartment of Pharmacy, Japanese Red Cross Otsu HospitalKouheiYamagiwaDepartment of Pharmacy, Saiseikai Shiga HospitalKazuoSatoDepartment of Pharmacy, Japan Baptist HospitalHirokiHasegawaDepartment of Pharmacy, Rakuwakai Otowa HospitalNobuhikoUoshimaDepartment of Hematology, Japanese Red Cross Kyoto Daini HospitalYumiKitahiroDepartment of Pharmacy, Kobe University HospitalKanjiTomoganeDepartment of Pharmacy, Japanese Red Cross Kyoto Daini HospitalBackground Premedication with corticosteroids is recommended for prophylaxis against infusion-related reactions (IRRs) caused by obinutuzumab despite a lack of solid evidence regarding the dose of corticosteroids.<br>
Methods The incidence rates of IRR in the high-dose and low-dose corticosteroid groups were investigated and compared using Student’s t-test.Univariable and multivariable logistic regression analyses were performed on patients to explore the risk of developing IRRs with obinutuzumab.<br>
Results The incidence of IRRs in the high-dose and low-dose corticosteroid groups at the initial administration of obinutuzumab was 27.0% (41/152) and 48.4% (31/64), respectively, indicating that the high-dose group had a lower incidence of IRRs (p = 0.002). The incidence of IRRs at the initial administration of obinutuzumab was significantly associated with the administration of first-generation histamine 1 receptor antagonist (OR = 3.31, 95% CI: 1.16–9.47; reference: second-generation histamine 1 receptor antagonist), hydrocortisone (OR = 7.21, 95% CI: 1.57–33.15; reference: dexamethasone), and methylprednisolone (OR = 3.99, 95% CI :1.13–14.10; reference: dexamethasone), although no association was found with the lower dose of corticosteroids.<br>
Conclusions Although no association was found between corticosteroid dosage and IRR when considering multiple factors, dexamethasone may be a better option than hydrocortisone or methylprednisolone for preventing IRR. Additionally, second-generation H1-receptor antagonists may be a better option than first-generation drugs. Certain combinations of premedications may influence infusion reaction incidence.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1478-63622812026Real-world comparative effectiveness of sarilumab versus Janus kinase inhibitors as monotherapy in rheumatoid arthritis32ENYujiNozakiDepartment of Hematology and Rheumatology, Kindai University Faculty of MedicineKazuyaKishimotoDepartment of Hematology and Rheumatology, Kindai University Faculty of MedicineTetsuItamiDepartment of Hematology and Rheumatology, Kindai University Faculty of MedicineDaisukeTomitaDepartment of Hematology and Rheumatology, Kindai University Faculty of MedicineYumikoWadaDepartment of Internal Medicine (IV), Osaka Medical and Pharmaceutical UniversityTakuyaKotaniDepartment of Internal Medicine (IV), Osaka Medical and Pharmaceutical UniversityTohruTakeuchiDepartment of Internal Medicine (IV), Osaka Medical and Pharmaceutical UniversityToshihikoHidakaRheumatology Center, Miyazaki Zenjinkai HospitalShoichiHinoDepartment of Rheumatology and Clinical Immunology, Izumi City General Medical CenterToshiakiMiyamotoMiyamoto Internal Medicine and Rheumatology ClinicHirofumiMiyakeDepartment of General Internal Medicine, Tenri HospitalKazunariHattaDepartment of General Internal Medicine, Tenri HospitalKenjiMamotoDepartment of Orthopaedic Surgery, Graduate School of Medicine, Osaka Metropolitan UniversityYutaroYamadaCenter for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of MedicineTadashiOkanoCenter for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of MedicineTakaichiOkanoDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of MedicineJunSaegusaDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of MedicineMasahiroHoritaDepartment of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama UniversityKeiichiroNishidaLocomotive Pain Center, Faculty of Medical Development Field, Okayama UniversityKojiKinoshitaDepartment of Hematology and Rheumatology, Kindai University Faculty of MedicineShinyaRaiDepartment of Hematology and Rheumatology, Kindai University Faculty of MedicineBackground: Sarilumab (SAR), an interleukin-6 receptor inhibitor (IL-6Ri), and Janus kinase inhibitors (JAKi) are approved options for rheumatoid arthritis (RA) when methotrexate (MTX) cannot be used. Real-world evidence for MTX-free monotherapy remains limited.<br>
Methods: We conducted a multicenter retrospective cohort study of RA patients receiving SAR or JAKi as MTX-free monotherapy. To reduce confounding, 1:1 propensity score matching was performed in the overall cohort (n = 252, 126 per group) and separately within treatment-line strata: Phase 2 first-line biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs: 45 per group), Phase 3 second-line b/tsDMARDs (53 per group), and Phase 3 ≥ third-line b/tsDMARDs (47 per group). Outcomes over 12 months included drug retention, change in Clinical Disease Activity Index (CDAI), glucocorticoid (GC) tapering and discontinuation, low disease activity (LDA, CDAI ≤ 10), and safety profiles. Predictors of LDA were evaluated with logistic regression. This multicenter real-world.<br>
Results: Across matched strata by prior b/tsDMARDs, retention and CDAI change did not differ significantly between SAR and JAKi through 12 months. When classified by cause, adverse events (AEs)-related discontinuation was higher with JAKi, yielding lower AE-specific retention. Both groups demonstrated GC sparing overtime, with a greater increase in GC discontinuation for SAR than for JAKi in Phase 2. Baseline predictors of achieving LDA at 12 months included higher C-reactive protein (CRP) and platelet count (Plt) in both groups, with additional associations of younger age and lower hemoglobin (Hb) in the SAR. In safety analyses, overall AEs were less frequent with SAR than with JAKi, driven by lower risks of infection including herpes zoster, while other categories were similarly infrequent.<br>
Conclusion: SAR and JAKi showed no statistically significant differences in 12-month retention or disease control in MTX-free monotherapy settings. Higher CRP and Plt with lower Hb, particularly in younger patients, identified better response to SAR and support biomarker guided selection between IL-6Ri and JAKi. In Phase 2, GC discontinuation with SAR suggests a practical strategy to reduce AEs while maintaining efficacy. Prospective studies should validate these findings and define actionable thresholds.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0021-51552026Real-world six-month outcomes after switching from aflibercept 2 mg to aflibercept 8 mg for neovascular age-related macular degenerationENHiroyaKindoDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMio MorizaneHosokawaDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChihiroOuchiDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyoMatobaDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTetsuroMoritaDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunkoHayashiDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiMorizaneDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose To investigate 6-month outcomes in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept 2 mg to intravitreal aflibercept 8 mg.<br>
Study design Retrospective observational study.<br>
Methods We reviewed records of consecutive nAMD eyes switched from aflibercept 2 mg to 8 mg. In eyes continuing aflibercept 8 mg, best-corrected visual acuity (BCVA), treatment intervals, and anatomical/exudative parameters were evaluated at 6 months. In eyes that could not continue, reasons for discontinuation were examined.<br>
Results Forty-four eyes from 44 patients were included. At 6 months, 35 eyes (79.5%) continued and 9 (20.5%) discontinued aflibercept 8 mg. Discontinuing eyes had significantly shorter pre-switch treatment intervals and more frequent prior therapies than continuing eyes. In the continuation group, BCVA remained stable (median 0.05 to 0.00 logMAR, P = 0.351), while the treatment interval was significantly extended (median 7.0 to 9.0 weeks, P < 0.001). Central retinal thickness and pigment epithelial detachment height decreased significantly (P = 0.035 and P = 0.021, respectively). The proportion of eyes with subretinal fluid significantly decreased from 74.3 to 37.1% (P = 0.003). Of the discontinuations, 4 were due to worsening exudation and 5 to inability to extend to ≥8 weeks as required by labeling. No intraocular inflammation or serious adverse events occurred.<br>
Conclusions Switching to aflibercept 8 mg achieved anatomical improvements and longer treatment intervals in ~80% of nAMD cases, suggesting it may be a useful alternative to aflibercept 2 mg. However, continuation may be difficult in refractory cases requiring frequent injections before switching.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2041-48891612025TRPV2 in muscle satellite cells is crucial for skeletal muscle remodelling888ENYanzhuChenDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKimiakiKatanosakaDepartment of Biomedical Sciences, College of Life and Health Sciences, Chubu UniversityMakotoShibuyaDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYubingDongDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityLidanZhangLaboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of OsakaMotoiKanagawaDepartment of Cell Biology and Molecular Medicine, Ehime University Graduate School of MedicineSo-ichiroFukadaLaboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of OsakaKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiKatanosakaDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySkeletal muscle remodelling relies on muscle stem cells (MuSCs) for regeneration after injury and hypertrophy in response to mechanical loading. However, the mechanisms that trigger MuSC activation and proliferation remain unclear. Transient receptor potential vanilloid 2 (TRPV2) ion channels respond to insulin-like growth factor-1 and mechanical stimuli to regulate the biological characteristics of various cells. Using a temporally inducible MuSC-specific conditional knockout (cKO) mouse, we show that TRPV2 regulates MuSC function and is essential for muscle remodelling. In cultured myofibre, MuSCs express TRPV2 and exhibit Ca2+ responses to the TRPV2 agonists 2-aminoethoxydiphenyl borate and probenecid, which are abolished upon TRPV2 deletion. TRPV2-deficient MuSCs exhibit reduced paired box 7 (Pax7) expression and impaired proliferation, suggesting TRPV2 is a factor that regulates the early stage of MuSC function. Myotube formation in MuSCs was enhanced by overexpression of TRPV2 and suppressed by TRPV2 deficiency, suggesting that TRPV2 is a factor that promotes myogenesis. Muscle-administered cardiotoxin promoted muscle regeneration and resulted in the appearance of numerous Pax7-positive MuSCs between myofibres. MuSC-specific TRPV2 cKO mice exhibit substantially impaired muscle regeneration after cardiotoxin-induced injury, drastically reducing Pax7-positive MuSCs between myofibres. In floxed mice, mechanical loading via synergist ablation induces hypertrophy and greatly increases the number of myonuclei per myofibre. In contrast, MuSC-specific TRPV2 cKO mice show no changes in myofibre thickness or nuclear number, either at baseline or after mechanical loading. Mechanical loading of floxed mice increased TRPV2+/Pax7+ double-positive MuSCs, but MuSC-specific TRPV2 cKO mice showed no change. Additionally, MuSCs exhibit Ca2+ responses to hypo-osmotic stimuli, which are suppressed by TRPV2 inhibitors and TRPV2 deletion, suggesting that MuSCs exhibit TRPV2-dependent mechanical responses. These results establish TRPV2 as a critical regulator of MuSC-mediated muscle remodelling, an important finding that may lead to therapeutic strategies for muscle repair and adaptation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1435-245141112025The impact of liver transection depth on surgical difficulty in robotic versus laparoscopic limited liver resection (TAKUMI-5)22ENTomokazuFujiDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKoseiTakagiDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKazuyaYasuiDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineAteneItoDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasuoNagaiDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShoheiYokoyamaDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicinePurpose Although robotic liver resection (RLR) has gained popularity worldwide, limited liver resection remains the mainstay of RLR. This study aimed to investigate the effect of parameters, including liver transection depth (LTD), on surgical difficulty in limited RLR compared with limited laparoscopic liver resection (LLR).<br>
Methods This retrospective study included 105 patients who underwent limited RLR (n = 56) or LLR (n = 49) at our institution between January 2018 and December 2024. After comparing outcomes of RLR and LLR, multivariate analyses were performed to examine effect of LTD on surgical difficulty (defined as prolonged operative time). Moreover, outcomes stratified by LTD cut-off values were compared between the groups.<br>
Results Median LTD was similar between groups (RLR vs. LLR: 2.6 vs. 2.6 cm, P = 0.77). LTD was significantly correlated with operative time for both procedures (RLR, R² = 0.07, P = 0.042; LLR, R² = 0.08, P = 0.046). Multivariate analyses demonstrated that LLR (odds ratio, 6.9; P < 0.001) and LTD (odds ratio, 2.0; P = 0.004) were significant risk factors of surgical difficulty. Among patients with deeper LTD (> 2.5 cm), the RLR group had significantly shorter operative time (145 vs. 231 min, P < 0.001), less blood loss (nil vs. 100 mL, P = 0.006), and a higher rate of textbook outcomes (76.7% vs. 42.3%, P = 0.01).<br>
Conclusion This study investigated impact of LTD on surgical outcomes in patients who underwent limited RLR compared to those who underwent limited LLR. LTD may be a useful parameter for estimating surgical difficulty in limited RLR. Moreover, robotic surgery may be favorable for deeper and limited liver resections.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841762025Severe Anemia Caused by a Colorectal Lipoma With Central Erosions: A Case Reporte85768ENYusukeYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukiMatsumiDepartment of Gastroenterological Surgery, Okayama University HospitalKoWatanabeDepartment of Pathology, Okayama University HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesColorectal lipomas are benign tumors that are often asymptomatic and discovered incidentally. In most cases, they can be managed conservatively with observation. We report the case of a man in his 70s with a colorectal lipoma located in the cecum. An investigation into his severe anemia led to the suspicion that the cecal lipoma was the underlying cause. An ileocecal resection was performed. Erosions were observed at the center of the lipoma. Although small colorectal lipomas are generally asymptomatic and rarely cause anemia, periodic endoscopic examinations are recommended. These lesions should be considered in the differential diagnosis of lower gastrointestinal bleeding.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1435-245141112025Surgical outcomes and patient selection in nonagenarians with colon cancer: a comparative multi-institutional study of laparoscopic and open approaches21ENRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoeTakanagaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalRyoInadaDepartment of Surgery, Kochi Health Sciences CenterToshiakiToshimaDepartment of Surgery, Kagawa Rosai HospitalTsuyoshiOhtaniDepartment of Surgery, Saiseikai Okayama HospitalRyosukeYoshidaDepartment of Surgery, Okayama Rosai HospitalNaotoHoriDepartment of Surgery, Tottori Municipal HospitalKaoruShigemitsuDepartment of Surgery, Tsuyama Chuo HospitalSumiharuYamamotoDepartment of Surgery, Okayama City HospitalTetsushiKubotaDepartment of Surgery, Kobe Red Cross HospitalYukaOkanoDepartment of Surgery, Onomichi City HospitalTetsujiNobuhisaDepartment of Surgery, Himeji Red Cross HospitalFumitakaTaniguchiDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterWataruIshikawaDepartment of Surgery, Fukuyama City HospitalTatsuoMatsudaDepartment of Surgery, Matsuda HospitalTatsuoUmeokaDepartment of Surgery, Matsuyama City HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSetouchi Colorectal Neoplasm Registration study group collaboratorsPurpose The appropriate surgical approach for colon cancer (CC) in nonagenarian patients remains a subject of clinical debate. This study aimed to compare the short-term outcomes of laparoscopic (Lap) versus open (Open) surgery in patients aged ≥ 90 years with resectable colon cancer.<br>
Methods This multi-institutional retrospective cohort study included oldest-old patientswith pathological Stage II/III CC who underwent elective surgery at 15 hospitals between 2011 and 2022. Patients with rectal cancer, Stage 0/I/IV disease, or emergency surgery were excluded. To address selection bias, inverse-probability-weighted regression adjustment and stabilized inverse probability of treatment weighting (sIPTW) were applied. The primary outcome was postoperative complications; secondary outcomes included overall survival (OS).<br>
Results Median age was 92 years in both groups. Before adjustment, the Lap group had a higher proportion of female patients (p = 0.038) and lower ASA scores (p = 0.01). Laparoscopic surgery was associated with a significantly longer operative time (220 vs. 171 min, p = 0.046) but less intraoperative blood loss (10 vs. 78 mL, p < 0.01). Postoperative complication rates were comparable (Lap: 31.8%, Open: 33.8%), while the Lap group had a significantly shorter hospital stay (13 vs. 17 days, p < 0.01). D3 lymph node dissection was more frequently performed in the Lap group (p < 0.01). After sIPTW, overall survival did not differ significantly between groups (p = 0.61).<br>
Conclusion Both laparoscopic and open surgery are feasible options for selected nonagenarians with colon cancer. Laparoscopic surgery may offer benefits in terms of reduced blood loss and shorter hospitalization, despite longer operative times. Careful patient selection considering frailty and comorbidities is essential in determining the most appropriate surgical approach.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2038-131X2025Early C-reactive protein as a predictive biomarker for postoperative complications following robot-assisted surgery for rectal cancerENFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuseiTakahashiDepartment of Surgery, NHO Fukuyama Medical CenterHirokiOkabayashiDepartment of Surgery, NHO Fukuyama Medical CenterMasashiUtsumiDepartment of Surgery, NHO Fukuyama Medical CenterHideakiMiyasoDepartment of Surgery, NHO Fukuyama Medical CenterRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalMasaruInagakiDepartment of Surgery, NHO Fukuyama Medical CenterThis retrospective cohort study aimed to assess the predictive value of early postoperative C-reactive protein (CRP) levels for complications following robot-assisted rectal surgery (RARS) for rectal cancer. We analyzed data from 117 consecutive patients who underwent elective RARS at Okayama University Hospital between September 2020 and January 2025. Serum CRP levels were routinely measured preoperatively and on postoperative days (POD) 1 and 4. The primary outcome was the occurrence of any postoperative complication within 30 days, classified according to the Clavien–Dindo grading system. Postoperative complications were observed in 26 patients, representing 22.2% of the cohort. Univariate analysis revealed that several factors were significantly associated with complications, including older age, higher ASA score, neoadjuvant therapy, stoma creation, prolonged operative time, and elevated CRP levels on POD1 and POD4. Notably, multivariate logistic regression analysis identified POD1 CRP as a robust independent predictor of overall postoperative complications (adjusted odds ratio 0.77, 95% confidence interval (CI) [0.63–0.93], p < 0.01). In the ROC analysis, the AUC was 0.735 (bootstrap bias-corrected 95% CI 0.544–0.848). The optimal cutoff value of POD1 CRP was 5.63 mg/dl, at which Youden’s index, yielding a sensitivity of 0.615 and specificity of 0.868. In conclusion, early postoperative measurement of CRP on POD1 serves as a valuable and independent biomarker for predicting complications following RARS for rectal cancer. Incorporating POD1 CRP into postoperative surveillance may facilitate the early identification of high-risk patients, thereby facilitating timely interventions and ultimately improving surgical outcomes in this patient population.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Comparative efficacy of immune checkpoint inhibitor combination therapies by metastatic site in metastatic renal cell carcinoma3303ENShingoToyodaDepartment of Urology, Faculty of Medicine, Kindai UniversityLanInokiDepartment of Urology, Faculty of Medicine, Kindai UniversityMamoruHashimotoDepartment of Urology, Faculty of Medicine, Kindai UniversityWataruFukuokayaDepartment of Urology, The Jikei University School of MedicineKeiichiroMoriDepartment of Urology, The Jikei University School of MedicineShingoNishimuraDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineRyoichiMaenosonoDepartment of Urology, Osaka Medical and Pharmaceutical UniversityTakehiroIwataDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKensukeBekkuDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakuhisaNukayaDepartment of Urology, Fujita-Health University School of MedicineTakafumiYanagisawaDepartment of Urology, The Jikei University School of MedicineTakuyaTsujinoDepartment of Urology, Osaka Medical and Pharmaceutical UniversityKazumasaKomuraDepartment of Urology, Kawasaki University School of MedicineKiyoshiTakaharaDepartment of Urology, Fujita-Health University School of MedicineTeruoInamotoDepartment of Urology, Hamamatsu University School of MedicineHaruhitoAzumaDepartment of Urology, Osaka Medical and Pharmaceutical UniversityKazutoshiFujitaDepartment of Urology, Faculty of Medicine, Kindai UniversityJK-FOOT study groupFew studies have investigated the efficacy of immuno-oncology (IO) combinations at different metastatic sites in renal cell carcinoma (RCC). We evaluated the differential efficacy of IO–IO and IO–tyrosine kinase inhibitor (TKI) combinations by metastatic site in metastatic RCC (mRCC). This retrospective multicenter study by the JK-FOOT Study Group included 579 patients with intermediate- or poor-risk mRCC (per International Metastatic RCC Database Consortium criteria) treated with first-line IO combinations between September 2018 and December 2024. Metastatic sites were lymph nodes, lungs, bones, liver, brain, and others. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoint was objective response rate. Efficacy was compared between IO–IO and IO–TKI for each site. For lymph node (n = 36), lung (n = 132), or brain (n = 16) metastases, OS or PFS was not significantly different between IO–IO and IO–TKI. In bone metastases (n = 80), OS tended to favor IO–TKI (P = 0.053). In liver metastases (n = 22), OS was significantly longer with IO–TKI (P = 0.011). IO–TKI may be a more appropriate first-line option than IO–IO for mRCC with bone or liver metastases, while efficacy is similar for other sites.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Objective assessment of cesarean section suturing techniques using a uterine simulator7456ENHikariNakatoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJotaMakiDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesChiakiKuriyamaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShujiroSakataDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKeiichiOishiDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAyanoSuemoriDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHikaruOobaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomohiroMitomaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasakazuKatoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSakurakoMishimaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAkikoOhiraDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoeKirinoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesErikoEtoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHisashiMasuyamaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesCesarean wound healing is influenced by surgeon experience, suture type, and technique. This study utilized a simulation model to quantify these effects. Obstetricians–gynecologists and junior residents performed two-layer continuous suturing on uterine models, forming eight groups based on experience level (expert, novice), suture type (conventional, barbed), and technique (Albert–Lembert, layer-to-layer). The ideal wound condition was defined as that achieved by an expert using barbed sutures and the layer-to-layer technique. Wound characteristics were quantified and compared to this ideal. Experts using barbed sutures in Albert–Lembert suturing showed higher wound density but greater deformation and larger endometrial openings (both P < 0.01). Novices using barbed sutures in Albert–Lembert suturing showed similar wound density but significantly greater deformation and opening (both P < 0.01). Novices using conventional sutures in layer-to-layer suturing showed the lowest wound density and longest suturing time (both P < 0.01). Notably, novices using barbed sutures achieved wound characteristics comparable to experts using conventional sutures in Albert–Lembert suturing and results closer to the ideal in layer-to-layer suturing. These findings establish a quantifiable standard for cesarean suturing and suggest that optimizing suture types and techniques may help compensate for differences in surgical expertise.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1863-99415212026Preferential sacral fracture sites in fragility fractures of the pelvis type IVb and comparison of internal fixation methods: CT-based morphological mapping and finite element analysis72ENShuichiNaniwaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasanoriYorimitsuDepartment of Musculoskeletal Traumatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University,TsubasaHasegawaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeruhikoAndoDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyuichiroOkudaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShiroFukuokaDepartment of Orthopaedic Surgery, Kagawa Prefectural Central HospitalYusukeMochizukiDepartment of Emergency Health Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYasuakiYamakawaDepartment of Orthopaedic Surgery, Kochi Health Sciences CenterRyuichiNakaharaDepartment of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShiroHanakawaDepartment of Orthopaedic Surgery, Okayama Saidaiji HospitalToshifumiOzakiDepartment of Orthopedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose Fragility fractures of the pelvis (FFP) classified as Rommens-Hoffman type IVb are associated with spinopelvic dissociation and are generally considered to require surgical intervention. This study aimed to clarify the localization patterns of FFP type IVb and compare the biomechanical stability of different internal fixation techniques.<br>
Methods In this retrospective study, morphologic mapping of sacral fracture lines was performed in 36 patients with FFP type IVb. Based on the mapping results, a finite element (FE) model of FFP type IVb was developed to evaluate the biomechanical stability of ilio-sacral screw (ISS) fixation, trans-sacral screw (TSS) fixation, spinopelvic fixation (SPF; On each side, L5 pedicle screw was connected to two iliac screws with a rod, and the bilateral constructs were linked using a cross-connector.), and bilateral triangular fixation (one TSS at S1 combined with SPF mentioned above) using finite element analysis (FEA).<br>
Results Morphologic mapping showed that the sacrum fracture transverse line tended to pass between the S1-2 transverse lines. Although bilateral triangular fixation and SPF provided the highest stability in both U-type and H-type fractures, a TSS for U-type and two TSSs for H-type also demonstrated comparable levels of stability. ISS-based methods showed greater displacements.<br>
Conclusion TSS-based fixation may provide stability comparable to bilateral triangular fixation and SPF in FFP type IVb, with less invasiveness when anatomy permits. Further studies are needed to optimize treatment strategies for this complex injury.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-22612512025Prognostic value of right atrial strain in patients with chronic heart failure908ENRieNakayamaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of MedicineYoichiTakayaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of MedicineMitsutakaNakashimaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of MedicineTakahiroNishiharaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of MedicineNorihisaTohDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of MedicineMiyoshiToruDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of MedicineKazufumiNakamuraDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of MedicineShinsukeYuasaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Science, Okayama University Graduate School of MedicineAims Right ventricular dysfunction is a well-established prognostic marker in patients with heart failure (HF). However, the prognostic significance of right atrial (RA) function remains unclear. Given its sensitivity to systemic congestion, RA function may provide additional insights into HF disease progression and management. This study aimed to investigate whether RA reservoir function serves as an independent prognostic indicator in patients with chronic HF.<br>
Methods A total of 613 patients with chronic HF and a left ventricular (LV) ejection fraction of less than 50% who underwent echocardiographic assessment at Okayama University Hospital between January 2018 and March 2023 were included (median age: 68 (58–76) years; 69% male). RA reservoir function was quantified using two-dimensional speckle-tracking echocardiography. The primary endpoint was cardiovascular death or HF-related hospitalization. Kaplan–Meier survival analysis was performed to examine the association between RA reservoir function and clinical outcomes.<br>
Results During a median follow-up period of 41 months (range: 12–91 months), 119 patients experienced cardiac events. Compared with event-free patients, those with cardiac events exhibited a significantly larger RA maximum volume index (38 mL/m2 vs. 31 mL/m2, P < 0.001) and a significantly lower RA reservoir longitudinal strain (RASr) (17% vs. 22%, P < 0.001). Kaplan–Meier analysis demonstrated that patients with RASr ≤ 20% had significantly poorer event-free survival than those with RASr > 20%, even without RA volume enlargement (log-rank test, P < 0.001). Multivariate Cox regression analysis identified RASr as an independent predictor of cardiac events (hazard ratio: 0.95, 95% confidence interval: 0.93 to 0.97, P < 0.001).<br>
Conclusions In patients who experienced adverse cardiac events, a reduced RASr and an increased RA maximum volume were observed. Furthermore, a reduced RASr was independently associated with an increased risk of cardiovascular death and HF-related hospitalization in patients with chronic HF and LV dysfunction. These findings indicate that RASr may serve as a valuable prognostic marker for the risk stratification and management of chronic HF.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1364-67532712026Compound heterozygosity of a novel missense variant and exonic deletion in hypomyelinating leukodystrophy 1516ENAkihikoMitsutakeDepartment of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of NeurologyTakashiMatsukawaDepartment of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of NeurologyKentaOrimoDepartment of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of NeurologyKunihiroUedaDepartment of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of NeurologyTomonariSekiDepartment of Neurology, Tokyo Teishin HospitalYasushiShiioDepartment of Neurology, Tokyo Teishin HospitalJunMitsuiDepartment of Precision Medicine Neurology, Graduate School of Medicine, The University of TokyoHiroyukiIshiuraDepartment of Neurology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHarushiMoriDepartment of Radiology, School of Medicine, Jichi Medical University,ShojiTsujiInstitute of Medical Genomics, International University of Health and WelfareTatsushiTodaDepartment of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Department of NeurologyHypomyelinating leukodystrophy 15 (HLD15) results from biallelic pathogenic variants in EPRS1, but exonic deletions have not been reported. We describe a 40-year-old woman with mild intellectual disability, ataxia, dystonia, and MRI showing hypomyelination. Whole-exome sequencing identified a heterozygous missense variant in the prolyl-tRNA synthetase domain of EPRS1 (c.3430 C > G; p.Leu1144Val, NM_004446.3), without second variant. Whole-genome sequencing revealed a heterozygous 220-bp deletion spanning exon 15 (c.1743-30_1932del), and segregation analysis confirmed compound heterozygosity. RT-PCR from lymphoblastoid cells demonstrated exon-15 skipping leading to a frameshift (p.Asn582Serfs*10) and nonsense-mediated decay, leaving predominant expression of the paternally inherited missense allele. These findings support loss-of-function for the deletion and classify c.3430 C > G as likely pathogenic under ACMG/AMP criteria (PM1, PM2, PM3, PP3). This case represents the first exonic deletion reported in EPRS1. The relatively mild, adult-onset phenotype broadens both mutational and clinical spectra of HLD15 and highlights the importance of structural-variant analNo potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1546-00962312025Comparison of clinical practices during the transitional and young adult phases between patients with oligoarticular/polyarticular juvenile idiopathic arthritis and those with rheumatoid arthritis in Japan120ENShoMoriDivision of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of MedicineKosukeShabanaDepartment of Pediatrics, Osaka Medical and Pharmaceutical UniversityToshihiroMatsuiDepartment of Rheumatology Research, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National HospitalTomoNozawaDepartment of Pediatrics, Graduate School of Medicine, Yokohama City UniversityYukoSugitaDepartment of Pediatrics, Osaka Medical and Pharmaceutical UniversityMinakoTomiitaDepartment of Allergy and Rheumatology, Chiba Children’s HospitalYasuoNakagishiDepartment of Pediatric Rheumatology, Hyogo Prefectural Kobe Children’s HospitalYuichiYamasakiDepartment of Pediatrics, Kagoshima University HospitalHiroakiUmebayashiDepartment of General Pediatrics, Miyagi Children’s HospitalMasatoYashiroDepartment of Pediatrics, Okayama University HospitalNaomiIwataDepartment of Infection and Immunology, Allergy and Immunology Center, Aichi Children’s Health and Medical CenterJunkoYasumuraDepartment of Pediatrics, Hiroshima University Graduate School of Biomedical and Health SciencesHiroyukiWakiguchiDepartment of Pediatrics, Yamaguchi University Graduate School of MedicineTakeshiYamamotoDepartment of Pediatrics, Chiba University Graduate School of MedicineShunichiroTakezakiDepartment of Pediatrics, Faculty of Medicinea and Graduate School of Medicine, Hokkaido UniversityYukaOkuraCenter for Pediatric Allergy and Rheumatology, KKR Sapporo Medical CenterTadafumiYokoyamaDepartment of Pediatrics, Kanazawa UniversityMasakiShimizuDepartment of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science TokyoMasahiroHirayamaDepartment of Pediatrics, Mie University Graduate School of MedicineShigetoTohmaDepartment of Rheumatology, National Hospital Organization Tokyo National HospitalNamiOkamotoDepartment of Pediatrics, Osaka Medical and Pharmaceutical UniversityMasaakiMoriDivision of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of MedicineBackground Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition that frequently persists into adulthood, posing long-term challenges in disease control and quality of life. However, clinical management during the transitional and young adult phases remains insufficiently characterized, especially in comparison with adult-onset rheumatoid arthritis (RA). This study aimed to compare disease activity, medication use, and treatment practices between patients with oligoarticular/polyarticular JIA and those with RA, focusing on individuals aged 16–30 years.<br>
Methods Data were derived from two nationwide multicenter databases in Japan—NinJa (National Database of Rheumatic Diseases in Japan) for RA and CoNinJa (a pediatric counterpart of NinJa) for JIA. A total of 176 JIA and 152 RA patients, all aged 16–30 years, were analyzed. Clinical parameters, disease activity indices, and medication profiles were compared using the Mann–Whitney U test and Fisher’s exact test.<br>
Results Compared to RA patients, JIA patients demonstrated significantly lower disease activity (median SDAI 0.6 vs. 2.4) and higher remission rates, particularly Boolean remission (70% vs. 44%) (p < 0.001). MTX usage was less frequent in JIA (49% vs. 68%, p < 0.001), whereas biologic use was notably more common (69% vs. 38%, p < 0.001), with 31% involving off-label prescriptions. Among patients in CDAI remission, biologic monotherapy was observed more frequently in JIA (29% vs. 7%, p < 0.001). Discontinuation of MTX was most commonly attributed to disease improvement (58%) or gastrointestinal intolerance (nausea, 29%). Subcutaneous tocilizumab, though unapproved for JIA in Japan, had the lowest discontinuation rate (4%), suggesting favorable tolerability.<br>
Conclusions Despite an overlap in age, patients with JIA and RA exhibit distinct disease characteristics and therapeutic patterns. These differences underscore the need to expand approved treatment options for JIA, promote equitable access to biologics, and strengthen transitional care frameworks. Further research is warranted to explore long-term outcomes, reproductive health considerations, and socioeconomic barriers that influence treatment continuity in young adults with childhood-onset arthritis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841772025The Challenge of Diagnosing Scirrhous Gastric Cancer by Endoscopic Biopsy: A Case Reporte87334ENYukaIkedaDepartment of Internal Medicine, Clinic IkedaDepartment of Internal Medicine, Clinic IkedaMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTadashiYoshinoDepartment of Pathology, Okayama UniversityTakehiroTanakaDepartment of Pathology, Okayama University HospitalNobumasaIkedaDepartment of Internal Medicine, Clinic IkedaMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesScirrhous gastric cancer, also known as linitis plastica, is a rare and aggressive subtype of gastric carcinoma that poses significant diagnostic challenges due to its submucosal infiltration and often normal-appearing mucosa. We report a case involving a 30-year-old Japanese woman who presented with a six-month history of epigastric pain and postprandial vomiting. Initial endoscopic examination revealed erythema and mucosal swelling, with limited antral distensibility and resistance during duodenal intubation. Despite 12 mucosal biopsies, histopathological examination revealed no evidence of malignancy. Given the strong clinical and endoscopic suspicion of scirrhous gastric cancer, additional deep sections and immunohistochemical staining were performed. These revealed scattered signet-ring cell carcinoma and poorly differentiated adenocarcinoma, with positive immunostaining for p53 and Ki67. The patient underwent total gastrectomy, and the diagnosis of scirrhous gastric cancer was confirmed on the resected specimen. This case highlights the importance of a high index of clinical suspicion, close collaboration between endoscopists and pathologists, and the utility of ancillary diagnostic tools, such as immunohistochemistry, in identifying subepithelial gastric malignancies that may be missed on conventional biopsy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0916-96362026Distinct associations of blood pressure phenotypes with subclinical cerebrovascular disease and coronary artery calcification in Japanese menENNominBayaraaNCD Epidemiology Research Center, Shiga University of Medical ScienceYuichiroYanoNCD Epidemiology Research Center, Shiga University of Medical ScienceAyaKadotaNCD Epidemiology Research Center, Shiga University of Medical ScienceNazar MohdAzaharTran Ngoc HoangPhapNational Institutes of Biomedical Innovation, Health and NutritionTakashiHisamatsuDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeikoKondoNCD Epidemiology Research Center, Shiga University of Medical ScienceSayukiToriiNCD Epidemiology Research Center, Shiga University of Medical ScienceAkiraFujiyoshiDepartment of Hygiene, School of Medicine, Wakayama Medical UniversityTakayoshiOhkuboDepartment of Hygiene and Public Health, Teikyo University School of MedicineAkihikoShiinoMolecular Neuroscience Research Center, Shiga University of Medical ScienceKazuhikoNozakiDepartment of Neurosurgery, Shiga University of Medical ScienceKatsuyukiMiuraNCD Epidemiology Research Center, Shiga University of Medical ScienceHypertension, encompassing white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH), is an established risk factor for cardiovascular diseases (CVDs), including atherosclerosis. However, among the general population, findings on which target organ is affected by the different phenotypes of hypertension remain unclear. In this community-based observational study of Shiga Epidemiological Study of Subclinical Atherosclerosis, 740 Japanese men underwent brain magnetic resonance imaging to assess the presence of lacunar infarction, white-matter hyperintensities, microbleeds, and intracranial artery stenosis (ICAS) between 2012 and 2015. They also underwent office blood pressure (BP) measurements, home BP monitoring for at least five consecutive days, and coronary artery calcification (CAC) assessments between 2010 and 2014. The final analysis included 686 participants without a history of CVDs. Of the 686 participants, the mean age ( ± SD) was 68.0 ( ± 8.3) years, and 39.3% were taking antihypertensive medication. In multivariable-adjusted models, each of WCH, MH, and SH was significantly associated with a higher risk of microbleeds compared to normotension. However, the association of WCH with microbleeds was evident only among those on antihypertensive medication (adjusted odds ratio [OR] 6.75 [95% CI 1.83–24.86]) and absent in those not on such medication (adjusted OR 1.20 [95% CI 0.31–4.73]). SH was associated with lacunar infarction, ICAS, and CAC. Among Japanese men, WCH, MH, SH were associated with subclinical cerebrovascular diseases, whereas only SH was associated with CAC. Moreover, any elevated BP phenotype increased the risk of microbleeds. Our findings suggest that different hypertension phenotypes distinctly affect target organs, particularly the brain and heart.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1345-26302026Tabtoxin biosynthetic gene cluster in Pseudomonas syringae pv. tabaci 6605 genomic island 1 (GI-1Pta6605) is required for severe disease symptomsENKotomiKunishiThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNorikaFujisawaThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHidenoriMatsuiThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNanamiSakataThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshiteruNoutoshiThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityKazuhiroToyodaThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYukiIchinoseThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityOne of the genomic islands in Pseudomonas syringae pv. tabaci 6605 (GI-1Pta6605) has been identified as a pathogenicity island required for virulence because the deletion almost completely eliminated disease symptoms in inoculation tests at 4 × 105 CFU/ml. GI-1Pta6605 contains four cargo regions (CRs) named CR-1 to CR-4. The ∆CR-4 mutant did not produce tabtoxin like ∆GI-1 and disease symptoms did not develop in tobacco. However, it grew, although to a lesser extent than the wild-type strain. These results indicate that the tabtoxin biosynthetic gene cluster in GI-1 is required for virulence but not for establishment of compatibility.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0969-023932162025Development of sulfation for cellulose pulp to change its fiber morphology and appearance to transparent in water96639677ENAyatoNishimuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTetsuyaUchidaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityCellulose pulp (CP) is composed mainly of cellulose which is one of the most useful and sustainable natural polymers. Cellulose-based materials, such as completely dispersed nanofibers and water-soluble cellulose, are transparent in water. Additionally, chemical modification of CP has been employed as a pretreatment for the preparation of nanofibers and to impart absorption properties derived from anionic functional groups. However, little is known about chemically modified CPs comprising micron-scale fibers that are transparent in water.In this study, we synthesized transparent sulfated cellulose pulp (TSCP) that exhibits good dispersion stability, high transparency in water, and highly swollen fiber structures. The sulfation method involved heating sulfamic acid and urea supported on CP. TSCP synthesized using a sulfamic acid amount relative to CP (Q) of 18.5, a molar ratio of urea to sulfamic acid (R) of 0.80, and a reaction temperature of 140 °C exhibited the highest total light transmittance (94.7%) in water, a degree of polymerization (535), and amount of sulfate groups (1.73 mmol/g). Polarization microscopy confirmed that most TSCP fibers swelled in water along the fiber width direction. The structure of hydrous-state TSCP was further confirmed using low-vacuum scanning electron microscopy. The maximum fiber width of the swollen TSCP reached 122 μm, which was approximately six times than that of CP. The crystallinity was equivalent to that of the original CP with a Cellulose I-type crystalline structure. This transparent, hydrous-state TSCP, comprising predominantly swollen CP fibers, demonstrates potential for applications as a transparent material.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Calcium ions play a critical role in calcification of Corynebacterium matruchotii4591ENNaokoOharaDepartment of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMidoriOgawaDepartment of Microbiology, School of Medicine, University of Occupational and Environmental HealthKatsukiTakebeDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIkueTosaDepartment of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySerinaOnoDepartment of Operative Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMitsumasaSaitoDepartment of Microbiology, School of Medicine, University of Occupational and Environmental HealthNaoyaOharaDepartment of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDental calculus is a hardened deposit composed of calcium phosphate precipitated within dental plaque. While the involvement of dental calculus in the progression of periodontal disease is well established, many aspects of its formation process remain poorly understood. In this study, we focused on Corynebacterium matruchotii, a key bacterium involved in dental calculus formation, and investigated the role of calcium ions in calcification, as well as the associated internal and external changes in the bacterium through long-term observation. In the absence of calcium ions, no intracellular calcification was observed, and the lipid bilayer with the formation of holes in bacterial body was evident. In contrast, in the presence of calcium ions, lipid bilayer remained intact, and intracellular needle- and plate- like crystals were formed. Furthermore, calcified C. matruchotii showed increased flocculation compared to non-calcified C. matruchotii. These results indicate that the influx of calcium ions is essential for intracellular calcification. Calcium ions entry appears to reinforce the integrity of the lipid bilayer, providing a stable intracellular environment conductive to calcification. Moreover, calcified C. matruchotii may contribute to the nucleation of dental calculus by forming aggregates composed of both bacterial components and calcified material.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1123-63372912025Safety and feasibility of D3 lymph node dissection in oldest-old patients undergoing colorectal cancer surgery: a multi-institutional, retrospective analysis146ENR.InadaDepartment of Surgery, Kochi Health Sciences CenterF.TeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesT.MitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalS.TakanagaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesT.ToshimaDepartment of Surgery, Kagawa Rosai HospitalT.OhtaniDepartment of Surgery, Saiseikai Okayama HospitalR.YoshidaDepartment of Surgery, Okayama Rosai HospitalN.HoriDepartment of Surgery, Tottori Municipal HospitalK.ShigemitsuDepartment of Surgery, Tsuyama Chuo HospitalS.YamamotoDepartment of Surgery, Okayama City HospitalT.KubotaDepartment of Surgery, Kobe Red Cross HospitalY.OkanoDepartment of Surgery, Onomichi City HospitalT.NobuhisaDepartment of Surgery, Himeji Red Cross HospitalF.TaniguchiDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterW.IshikawaDepartment of Surgery, Fukuyama City HospitalR.ShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesT.MatsudaDepartment of Surgery, Matsuda HospitalT.UmeokaDepartment of Surgery, Matsuyama City HospitalT.FujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSetouchi Colorectal Neoplasm Registration Study Group CollaboratorsBackground Colorectal cancer (CRC) is a significant health burden, with lymph node dissection (LND) playing a critical role in staging and guiding treatment. However, the optimal extent of LND for the oldest-old population (aged ≥ 90 years) remains undefined because of insufficient targeted clinical data. This study aimed to compare the short-term outcomes of D3 versus non-D3 LND in Stage II–III CRC in oldest-old patients.<br>
Methods This retrospective cohort study utilized data from the Setouchi Colorectal Neoplasm Registration database, including 282 oldest-old patients with CRC treated between 2011 and 2022. Patients were stratified into D3 and non-D3 LND groups, with inverse-probability-weighted regression adjustment implemented to address potential confounding factors. Postoperative complications and hospital stays were analyzed using regression models and descriptive statistics.<br>
Results D3 LND resulted in significantly higher lymph node harvests in both Stage II and Stage III patients (p < 0.01). There were no significant differences in overall or major postoperative complications between D3 and non-D3 groups. Hospital stays were comparable for Stage II patients but shorter for Stage III patients in the D3 group (p < 0.01). Complication rates ranged from 28% to 47.7%, with surgical site infections and pneumonia being the most common.<br>
Conclusions D3 LND can be safely performed in oldest-old patients with CRC without increasing postoperative complications or extending hospital stays. These findings support the feasibility of extensive LND in this age grNo potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417112025A Case of Psoas Abscess Diagnosed With Oral Bacteria as the Causative Pathogene97584ENKokiUmemoriOral and Maxillofacial Surgery, Okayama University Graduate School of MedicineKyoichiObataOral and Maxillofacial Surgery, Okayama University Graduate School of MedicineMayumiYaoDentistry and Dental Surgery, Tsuyama Central HospitalKojiFujitaGeneral Internal Medicine and Infectious Diseases, Tsuyama Central HospitalSoichiroIbaragiOral and Maxillofacial Surgery, Okayama University Graduate School of MedicineWe report a rare case of a psoas abscess in an 87-year-old woman, in which oral commensal bacteria may have disseminated hematogenously from a chronic oral infection site and served as the causative pathogens. The patient presented with persistent left buttock pain, fever, and swelling, and imaging revealed a fracture of the left iliac bone with an associated psoas abscess. Bacterial cultures identified Streptococcus oralis and Pseudomonas aeruginosa. Her symptoms improved following antibiotic therapy and CT-guided drainage. Although the presence of P. aeruginosa in the oral cavity is generally considered transient, it has been isolated from the oral cavities of elderly and immunocompromised individuals. In the absence of lacerations or other direct portals of entry, and considering the identification of both pathogens, the oral cavity was regarded as the most likely source of infection. This case highlights the importance of correlating culture results with the most probable source of infection to improve the prognosis of systemic infections.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841832026A Rare Association of Congenital Glaucoma and Retinitis Pigmentosa: A 22-Year Follow-Up Casee105012ENToshihikoMatsuoOphthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityPrimary congenital glaucoma is a rare congenital disease with a genetic background that shows high intraocular pressure due to ocular outflow anomalies. Retinitis pigmentosa is a predominant form of inherited retinal disorders. In this study, we present the case of a patient with primary congenital glaucoma in association with retinitis pigmentosa. A four-month-old female baby was brought to the emergency department due to corneal opacity in the left eye. The intraocular pressure measured by a hand-held applanation tonometer was 40 mmHg in the right eye and 36 mmHg in the left eye. She was otherwise healthy and diagnosed with primary congenital glaucoma. She immediately underwent trabeculotomy ab externo in both eyes under general anesthesia, and the intraocular pressure was lowered to 15 mmHg in the right eye and 12 mmHg in the left eye three weeks later. At the age of nine months, she was found to have retinal degeneration along the upper and lower vascular arcades of the fundus in both eyes and was diagnosed with retinitis pigmentosa. At the age of one year and 10 months, the visual acuity was measured at 0.2 in the right eye and 0.2 in the left eye for the first time by a preferential looking procedure. The intraocular pressure was 9 mmHg in both eyes under sedation, and she did not use any topical medication. At the age of three years and three months, the uncorrected visual acuity and best-corrected visual acuity with myopic astigmatism correction were 0.1 and 0.15, respectively, in the right eye and 0.6 and 0.7, respectively, in the left eye. Occlusion therapy with an eye patch over the left eye for one hour daily was started. At the age of four years and 10 months, the best-corrected visual acuity was 0.7 in both eyes. At the age of six years, occlusion therapy was discontinued, and full-correction glasses were prescribed, based on cycloplegic refraction. The visual acuity in the right eye decreased to 0.3 at the age of 11 years and further to 0.1 at the age of 12 years, while the visual acuity in the left eye remained 0.8. Afterwards, she maintained a visual acuity of 0.1 in the right eye and 0.8 in the left eye until the age of 22 years. An incidental presence of primary congenital glaucoma in this patient led to the detection of retinitis pigmentosa in earlier years and allowed long-term follow-up for 22 years. Even though genetic testing was not performed for this patient, the abnormal function of primary cilia, designated as ciliopathy, might explain the co-occurrence of primary congenital glaucoma and retinitis pigmentosa.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1746-61482212026Genetic and phenotypic identities of Staphylococcus coagulans isolated from pustules of dogs with superficial bacterial folliculitis98ENTakafumiOsumiAnimal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyYuukiShinomiyaDepartment of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyThamonwanWanganuttaraDepartment of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIchiroImanishiKimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount SinaiYotaroShimazakiAnimal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyKeitaIyori1sec Co. Ltd.YoichiToyoda1sec Co. Ltd.KaoriIdeAnimal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyJumpeiUchiyamaDepartment of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKojiNishifujiAnimal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and TechnologyBackground Staphylococcus coagulans, formerly called Staphylococcus schleiferi subsp. coagulans is the second most common isolate from skin lesions of dogs with superficial bacterial folliculitis (SBF). However, the clinical significance of S. coagulans in pustules of canine SBF remains uncertain. This study aimed to investigate the prevalence and genotypic and phenotypic diversity of S. coagulans isolated from pustules in two dogs with SBF.<br>
Results Two dogs with SBF were included in this study. S. schleiferi/coagulans was isolated as the sole organism from three pustules in case #1, whereas it coexisted with S. pseudintermedius in two of seven pustules in case #2. S. pseudintermedius was the sole organism in the remaining five pustules in case #2. Whole genome sequences revealed that all isolates tested were annotated as S. coagulans. The isolates from the same pustules exhibited identical genotypic and phenotypic profiles, indicating clonal multiplication. S. coagulans isolated from different pustules exhibited similar yet distinct genotypic and phenotypic profiles.<br>
Conclusions S. coagulans with identical genetic and phenotypic profiles can be identified as the sole pathogen or coexist with S. pseudintermedius in the pustules of the same dogs with SBF.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1757-22151912025Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer13ENAnnaRogachevskayaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolYusukeOtaniDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineAkiraOhtsuHarvard Medical SchoolVanessa D.ChinUMass Chan Medical School, UMass Memorial Medical CenterTirsoPeñaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolSeijiAraiDepartment of Urology, Gunma University Graduate School of MedicineShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineAtsushiFujimuraDepartment of Molecular Physiology, Faculty of Medicine, Graduate School of Medicine, Kagawa UniversityAtsushiTanakaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolBackground C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment.<br>
Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2. Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway.<br>
Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1546-00962412026TeMPRA: advancing continuing professional development in pediatric rheumatology in JapanENHiroyukiWakiguchiDivision of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of MedicineKunioHashimotoDepartment of Pediatrics, Nagasaki University Graduate School of Biomedical SciencesMasatoYashiroDepartment of Pediatrics, Okayama University HospitalKenichiNishimuraDepartment of Pediatrics, Yokohama City University Graduate School of MedicineTakasukeEbatoDepartment of Pediatrics, Kitasato UniversityKeijiAkamineDepartment of Nephrology and Rheumatology, Tokyo Metropolitan Children’s Medical CenterYojiUejimaDivision of Infectious Diseases and Immunology, Saitama Children’s Medical CenterTomomiSatoClinical Education Center for Physicians, Shiga University of Medical ScienceYuichiYamasakiDepartment of Pediatrics, Kagoshima University HospitalJunkoYasumuraDepartment of Pediatrics, Hiroshima Prefectural Hospital Organization Futabanosato Prefectural HospitalFumikoOkazakiDepartment of Pediatrics, Yamaguchi University Graduate School of MedicineToshitakaKizawaDepartment of Pediatrics, Japan Community Health Care Organization Sapporo Hokushin HospitalRyuheiYasuokaDepartment of Pediatrics, Hamamatsu University School of MedicineTomoakiIshikawaDepartment of Pediatrics, Nara Medical UniversityTakeshiYamamotoDepartment of Pediatrics, Chiba University Graduate School of MedicineYujiFujitaDepartment of Pediatrics, Dokkyo Medical UniversityNaohiroItohDepartment of Pediatrics, Faculty of Medical Sciences, University of FukuiAsamiTakasakiDepartment of Pediatrics, School of Medicine, University of ToyamaNodokaSakuraiDepartment of Pediatrics, NTT East Medical Center SapporoKazuoSuzukiSuzuki Kids ClinicTasukuTamaiDivision of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of MedicineNaokiHiranoDepartment of Public Health and Epidemiology, Faculty of Medicine, Oita UniversityNamiOkamotoDepartment of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and SafetyMasakiShimizuDepartment of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science TokyoBackground In the context of the global shortage of pediatric rheumatologists, mid-career specialists who can play key roles in regional education, research, and clinical practice have become increasingly important. In Japan, the Team of Mid-career Pediatric Rheumatologists Alliance (TeMPRA) was founded in 2014 to support continuing professional development (CPD) and foster collaboration among mid-career pediatric rheumatologists. The aim of this study was to characterize the current status and future perspectives of the TeMPRA members.<br>
Methods In 2024, a cross-sectional, web-based survey was conducted among all 37 active members of the TeMPRA across Japan. Data were collected on career trajectories, educational roles, research activities, clinical practices, and international engagement. Categorical variables were compared using appropriate statistical tests, with a significance level of 0.05.<br>
Results Responses were obtained from 35 members (response rate: 95%). Most respondents (71%) were affiliated with university hospitals, and 60% had > 10 years of experience in pediatric rheumatology. Compared with those working in community hospitals, respondents affiliated with university hospitals were significantly more likely to be involved in research activities (50% vs. 0%, P = 0.0261) and global professional contributions (88% vs. 0%, P < 0.0001). Overall, 54% of respondents were engaged in teaching students or early-career pediatric rheumatologists, while 43% were involved in clinical or basic research, most commonly focusing on juvenile idiopathic arthritis and systemic lupus erythematosus. Collectively, respondents were responsible for the care of 1,677 children with pediatric rheumatic diseases. While all respondents reported willingness to contribute to pediatric rheumatology at the regional level, 94% and 71% reported willingness to contribute at the national and global levels, respectively.<br>
Conclusions This nationwide survey highlights the substantial educational roles, research activities, and clinical practices of mid-career pediatric rheumatologists in Japan and suggests that the TeMPRA framework can serve as a valuable model for supporting CPD and workforce sustainability. Similar alliance-based approaches may be applicable in other countries facing comparable challenges in pediatric rheumatology.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1068-926532122025Mesenteric Route Superior Mesenteric Artery First Approach in Robot-Assisted Pancreatoduodenectomy89038905ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAteneItoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTsubasaYanagiharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground. The superior mesenteric artery (SMA) approach is crucial for the successful implementation of robot-assisted pancreatoduodenectomy (RPD). Herein, we present a novel technique, the mesenteric route SMA-first approach, for RPD.<br>
Patients and Methods. A 20-year-old woman with a 50 mm intraductal papillary mucinous neoplasm underwent RPD. As the tumor was large and located close to the mesenteric vessels, we developed the mesenteric route SMA-first approach.<br>
Results. Following the mesenteric Kocher maneuver, the mesenteric route SMA-first approach was applied. With appropriate retraction of the pancreatic head, dissection around the mesenteric vessels was performed and their branches were divided. The uncinate process dissection (PL, ph II) was performed via the mesenteric route. This approach facilitated dorsal dissection, particularly around the large tumor. After dissection of the hepatoduodenal ligament, the remaining pancreatic nerve plexus (PL ph I) was dissected. Finally, the pancreas was divided on the superior mesenteric vein, and the specimen was resected. Operative time was 390 min with minimal blood loss.<br>
Conclusions. The mesenteric route SMA-first approach enables uncinate process dissection via the mesenteric route. This technique may be a safe and feasible option for selected patients, such as nonobese individuals with a large pancreatic head tumor near major vessels.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1435-245141012025Robotic distal pancreatectomy using two-surgeon technique (TAKUMI-4): a technical note and initial outcomes171ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesPurpose With the increasing use of minimally invasive distal pancreatectomy, the use of robotic distal pancreatectomy (RDP) is also increasing worldwide. Standardized surgical protocols are essential for safe implementation of RDP. In this study, we present our surgical protocol and initial outcomes of RDP using “two-surgeon technique”.<br>
Methods Our standard RDP protocol included a two-surgeon technique for cooperation, rationality, and education. Short-term outcomes of RDP were also investigated. This retrospective study included 77 consecutive patients who underwent RDP at our institution between April 2021 and January 2025.<br>
Results The median operative time, estimated blood loss, and postoperative hospital stay were 214 min (interquartile range [IQR], 176–253), 10 mL (IQR, 0–50), and 9 days (IQR, 8–10), respectively. A textbook outcome was achieved in 84.4% of patients. Moreover, superior outcomes of RDP (n = 77) compared with those of laparoscopic distal pancreatectomy (n = 62) were confirmed in this study.<br>
Conclusion Using the two-surgeon technique, we successfully standardized and introduced the RDP program. The two-surgeon technique can contribute to the safe introduction of RDP and expansion of the program.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0930-27943952025Impact of visceral fat area on surgical difficulty during robotic distal pancreatectomy (TAKUMI-2)31373145ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotohikoYamadaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYasuoNagaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNoriyukiKanehiraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground: Difficulty scoring systems (DSS) have been developed to quantify the surgical complexity of laparoscopic distal pancreatectomy (LDP). However, few studies have validated these systems in the context of robotic distal pancreatectomy (RDP). Moreover, the impact of body composition on RDP outcomes remains unexplored. This study aimed to investigate the risk factors of surgical difficulty in RDP, including body composition.<br>
Methods: This retrospective study included 72 consecutive patients who underwent RDP at our institution between April 2021 and October 2024. Using a modified DSS for LDP, patients were divided into three difficulty index groups. The association between the difficulty index and outcomes was investigated. Multivariate analyses were performed to identify risk factors associated with surgical difficulty (prolonged operative time) in RDP.<br>
Results: Patients were classified into three difficulty index groups: low (n = 28), intermediate (n = 25), and high (n = 19). Operative time was significantly associated with the surgical index (P = 0.01). Moreover, visceral fat area (VFA) was significantly correlated with operative time (r2 = 0.10, P = 0.008). The multivariate analyses found that VFA (≥ 100 cm2) (odds ratio [OR] 5.03, 95% confidence interval [CI] 1.32–22.4, P = 0.02), malignancy (OR 4.92, 95% CI 1.50–18.9, P = 0.01), and pancreatic resection on the portal vein (OR 4.14, 95% CI 1.24–15.9, P = 0.02) were significant risk factors associated with surgical difficulty.<br>
Conclusion: VFA could be a novel and useful factor for assessing the surgical difficulty associated with RDP.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96253072025How to report and discuss subgroup analyses in clinical practice guidelines? Evaluation procedure of the clinical and statistical relevancy12591267ENKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalSatoruMiuraDepartment of Internal Medicine, Niigata Cancer Center HospitalYukoOyaDepartment of Respiratory Medicine and Allergy, Fujita Health UniversityTomohiroSakamotoDivision of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori UniversityKentaroTanakaGraduate School of Medical Sciences, Research Institute for Diseases of the Chest, Kyushu UniversityShunsukeTeraokaInternal Medicine III, Wakayama Medical UniversityMasahiroMoriseDepartment of Respiratory Medicine, Nagoya University Graduate School of MedicineSatoshiMoritaDepartment of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto UniversityThe results of subgroup analyses of clinical trials are important reference information when considering the generalizability of a study treatment, i.e., providing the best treatment for each individual patient. The results of subgroup analyses are often presented in publications, etc. as forest plots focusing on patient backgrounds. However, it is important to fully understand and grasp some of the issues involved in subgroup analyses and to interpret the results carefully to apply them in clinical practice. Although the literature includes some reports on how subgroup analyses should be evaluated and handled for the purpose of establishing medical practice guidelines, most of the papers have mainly evaluated the reliability of subgroup analyses from a statistical perspective; few of them have incorporated clinical importance in their evaluations. Therefore, in December 2019, we established a Subgroup Analysis Review Committee consisting of oncologists specializing in lung cancer treatment and statistical experts among the members of the Guidelines Review Committee of the Japanese Lung Cancer Association, with the aim of appropriately reflecting subgroup analysis in Japanese lung cancer practice guidelines. We developed a new evaluation strategy to incorporate clinical aspects as well as reliability assessment. Specifically, on the basis of a clinical and statistical review of the problems with subgroup analyses presented as clinical trial results, we developed criteria and procedures to ensure consistency and fairness in the citation of clinical guidelines.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841762025Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Studye86575ENShoSaekiDepartment of Respiratory Medicine, Kumamoto University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalShinyaSakataDepartment of Respiratory Medicine, Kumamoto University HospitalNaohiroOdaDepartment of Respiratory Medicine, Okayama University HospitalKojiInoueDepartment of Respiratory Medicine, Kitakyushu Municipal Medical CenterTomokiTamuraDepartment of Respiratory Medicine, Okayama University HospitalRyoToyozawaDepartment of Thoracic Oncology, National Hospital Organization Kyushu Cancer CenterDaijiroHaradaDepartment of Thoracic Oncology, National Hospital Organization Shikoku Cancer CenterKentaroTanakaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityKojiInoueDepartment of Respiratory Medicine, Ehime Prefectural Central HospitalYoshiyukiShioyamaRadiation Oncology, Ion Beam Therapy Center, SAGA HIMAT FoundationKenichiGembaDepartment of Respiratory Medicine, Chugoku Central HospitalTomonariSasakiDepartment of Radiation Oncology, Iizuka HospitalAkihiroBesshoDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalJunjiKishimotoCenter for Clinical and Translational Research, Kyushu University HospitalKuniakiKatsuiDepartment of Radiology, Division of Radiation Oncology, Kawasaki Medical SchoolKatsuyukiKiuraDepartment of Respiratory Medicine, Okayama University HospitalKenjiSugioThoracic and Breast Surgery, Oita UniversityBackground and objective: We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression.<br>
Materials and methods: We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients.<br>
Results: Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinib monotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported.<br>
Conclusions: Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841752025Pseudoachalasia Due to Malignant Pleural Mesothelioma Involving the Esophaguse84161ENManamiHondaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesWe report a rare case of pseudoachalasia secondary to malignant pleural mesothelioma involving the esophagus. A 66-year-old man presented with progressive dysphagia, weight loss, and postprandial hiccups. Endoscopic examination showed esophageal dilation with luminal narrowing at the esophagogastric junction, but no mucosal abnormalities. Computed tomography revealed an irregular-shaped mass extending from the peri-esophagogastric junction to the retroperitoneum, accompanied by pleural effusion, right-sided hydronephrosis, and multiple hepatic lesions. Endoscopic ultrasound-guided fine-needle aspiration from the mass lesion through the esophageal lumen revealed epithelioid malignant mesothelioma. This case highlights the importance of considering malignant mesothelioma in the differential diagnosis of pseudoachalasia, particularly when imaging reveals extrinsic esophageal compression without mucosal lesions.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841742025Gastrointestinal Stromal Tumors in the Stomach With Tumor Growth and Hemorrhage During Conservative Management: A Report of Two Casese82046ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesGastrointestinal stromal tumors (GISTs) are often detected incidentally during esophagogastroduodenoscopy. Although surgical resection is the standard treatment for GISTs, patients with significant comorbidities may not be eligible for surgery and are managed conservatively. Herein, we report two cases of gastric GISTs that were initially observed during the management of other comorbidities but subsequently became enlarged, resulting in gastrointestinal bleeding. These cases highlight the potential risks of tumor progression and bleeding in patients undergoing conservative management.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72571822025Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab363368ENShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHironariKatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKosakuMorimotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalIntrahepatic cholangiocarcinoma has a poor prognosis. In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed MLH1 pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30 months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the MLH1 pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841722025Gastric Metastasis of Renal Cell Carcinoma Initially Diagnosed by Esophagogastroduodenoscopye79651ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomohiroKamioDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShoichiroHirataDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHere, we report a rare case of renal cell carcinoma (RCC) initially detected as a gastric metastasis. A 58-year-old man with epigastric discomfort underwent esophagogastroduodenoscopy, which revealed a reddish semi-pedunculated lesion with a whitish coating. Biopsy and imaging confirmed clear cell RCC metastasis. Contrast-enhanced computed tomography (CT) revealed a primary renal tumor with pancreatic and lymph node metastases. Despite chemotherapy treatment, the patient died after 10 months. Gastric metastases from RCC, although rare, should be considered in highly vascular gastric lesions with white coatings. Clinicians must be vigilant for metastatic diseases with atypical gastric findings.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-13801912026Association of Wet-Bulb Globe Temperature with heat-related illness hospitalizations in Japan: a time-stratified, case-crossover study11ENYukaYamamuraDepartment of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical SciencesTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical SciencesTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical SciencesFumiyaSasaiDepartment of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical SciencesKoheiTokiokaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical SciencesTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical SciencesTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical SciencesJunKandaEmergency and Critical Care Medicine, Nippon Medical School Musashikosugi HospitalShojiYokoboriDepartment of Emergency and Critical Care Medicine, Nippon Medical SchoolHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical SciencesTakashiYorifujiDepartment of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical SciencesBackground Heat-related illnesses are a serious public health concern and are exacerbated by global warming. Wet-Bulb Globe Temperature (WBGT) is widely used as a heat stress indicator, but its clinical impact remains unclear. This study aimed to investigate the association between hourly variations in WBGT and the incidence of hospitalizations for heat-related illness in Japan using a nationwide database. By incorporating individual-level clinical data and performing stratified analyses, we sought to provide a more granular understanding of how heat exposure affects the risk of heat-related illness requiring hospitalization.<br>
Methods We conducted a time-stratified, case-crossover study using data collected from July to September in 2020 and 2021 in the Heatstroke STUDY registry. The inclusion criteria were patients registered in the Heatstroke STUDY registry, specifically hospitalized patients with heat-related illness who were transported to participating hospitals during the study period. Hourly WBGT values were assigned based on the nearest monitoring station to each hospital. Conditional logistic regression and distributed lag models were used to estimate associations between WBGT and the risk of hospitalization.<br>
Results A total of 1,653 heat-related illness hospitalizations were analyzed. The mean patient age was 67.9 years; 67.6% were male. Each 1 °C increase in WBGT at onset (hospital arrival) was associated with a significantly increased risk of hospitalization (OR 1.10, 95% CI: 1.05–1.15). The cumulative effect over the prior six hours was also significant (OR 1.56, 95% CI: 1.50–1.62). Compared with WBGT < 25 °C, adjusted ORs were 3.39 (25–27 °C), 8.81 (28–30 °C), and 22.10 (≥ 31 °C). Stratified analyses suggested stronger associations among several subgroups; however, only patients with mental disorders showed statistically significant effect modification, whereas elevated WBGT posed a risk across all groups.<br>
Conclusions Higher WBGT levels were associated with an increased risk of heat-related hospitalization. Although the effect appeared greater in some subgroups, only patients with mental disorders demonstrated statistically significant effect modification, suggesting elevated WBGT confers risk broadly.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417112025Association of Carboxyhemoglobin With Severity and Outcomes in Hypothermic Patients: A Retrospective Cohort Studye97962ENYuyaMiyoshiDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityIntroduction<br>
Carboxyhemoglobin (COHb), an endogenous marker of carbon monoxide production mediated by heme oxygenase-1, may reflect physiological stress responses in critically ill patients. However, its clinical relevance in accidental hypothermia remains unclear.<br>
<br>
Methods<br>
We conducted a single-center retrospective cohort study of adult patients admitted to the emergency ICU with accidental hypothermia between January 1, 2019, and March 31, 2025. Patients were categorized into low- and high-COHb groups based on median COHb levels upon emergency department arrival. Associations between COHb levels, disease severity (Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores), and 28-day mortality were analyzed using regression models adjusted for clinical confounders.<br>
<br>
Results<br>
Among the 88 patients, who had a median admission temperature of 28.7°C, 45 were classified into the low-COHb group and 43 into the high-COHb group, based on a median COHb level of 0.3%. Lower COHb levels on admission were significantly associated with higher APACHE II scores (β = −4.20; 95% CI, −7.56 to −0.85), but not with SOFA scores. Admission and minimum COHb levels were not associated with 28-day mortality. However, higher maximum COHb levels within the first 24 hours were independently associated with lower 28-day mortality (adjusted OR, 0.17; 95% CI, 0.023 to 0.93).<br>
<br>
Conclusions<br>
Lower COHb levels were associated with greater disease severity, and higher maximum COHb levels were associated with lower 28-day mortality. COHb may reflect systemic stress in accidental hypothermia, but its prognostic value appears limited.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96252026Turning pancreatic cancer from cold to hot: the promise of a p53-expressing oncolytic adenovirus (OBP-702)ENShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaCenter for Innovative Clinical Medicine, Okayama University HospitalMasashiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuoUrataOncolys BioPharma IncToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPancreatic cancer remains one of the most lethal malignancies, with limited therapeutic options and poor responsiveness to immune checkpoint inhibitors (ICIs). This resistance is largely attributed to its profoundly immunosuppressive and desmoplastic tumor microenvironment (TME), characterized by low tumor mutational burden, dense stroma, and abundant immunosuppressive cell populations. Therefore, strategies capable of enhancing tumor immunogenicity and overcoming immune evasion are urgently needed. Oncolytic virotherapy is a promising approach, offering not only tumor-selective cytotoxicity, but also potent immunomodulatory effects. Of these agents, Telomelysin (OBP-301, Suratadenoturev), a telomerase-specific oncolytic adenovirus, demonstrated clinical safety but limited efficacy in refractory tumors. To address this challenge, we developed OBP-702, a next-generation, p53-armed, oncolytic adenovirus designed to augment antitumor activity. Preclinical studies have shown that OBP-702 exerts robust cytotoxicity through multiple mechanisms, including p53-mediated apoptosis and autophagy, E1A–E2F1-mediated p21 suppression, and inhibition of oncogenic KRAS pathways. Importantly, OBP-702 induces strong immunogenic cell death, activates dendritic cells, and promotes tumor-specific T-cell responses, effectively converting immunologically “cold” pancreatic tumors into “hot” tumors. OBP-702 also remodels the immunosuppressive TME by reducing granulocyte–macrophage colony-stimulating factor (GM-CSF) secretion, suppressing myeloid-derived suppressor cells (MDSCs), and targeting stromal components, such as cancer-associated fibroblasts (CAFs). These effects contribute to enhanced responses to ICIs and standard chemotherapies. Given its multifaceted antitumor functions and ability to overcome key barriers in pancreatic cancer, OBP-702 represents a highly promising therapeutic candidate. A first-in-human clinical trial evaluating endoscopic ultrasonography-guided intratumoral injection of OBP-702 is currently in preparation, expected to advance clinical translation of this novel virotherapeutic strategy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2730-664X612026Effects of an oral exercise intervention on pre-frailty or frailty in older people: a randomized clinical trial96ENNorikoTakeuchiDepartment of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama UniversityNanamiSawadaSection of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu UniversitySakuraInadaDivision of Health Promotion, Okayama-City Health CenterManabuMoritaDepartment of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health CareDaisukeEkuniDepartment of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: Frailty is often experienced by older adults, which can lead to long-term health problems. We aimed to examine associations with improvements in nutritional status, sarcopenia (age-related loss of skeletal muscle mass and strength), and frailty in four groups with different oral exercise frequencies.<br>
Methods: We conducted a prospective, parallel multi-arm randomized controlled trial (Japan Registry of Clinical Trials (jRCT) 1062210063) to test the effects of oral exercise on frailty in older adults. Each intervention consisted of a standardized oral exercise protocol including neck exercises, lip exercises, and tongue movements, designed to improve oral function and reduce frailty. The primary outcome was the change in the number of frailty criteria from baseline to follow-up. Individuals aged ≥60 years were screened for frailty status using standardized criteria at the Department of Preventive Dentistry at Okayama University Hospital between October 2022 and December 2023. Those identified as pre-frailty or frailty were eligible and enrolled in the study. After screening 60 individuals, 58 eligible participants were randomly assigned using block randomization to one of four oral exercise frequency groups: 3 times/day & everyday, 3 times/day & 3 days/week, once/day & everyday, and once/day & 3 days/week. A two-way repeated measures analysis of variance was used to evaluate the impact of the four frequencies of oral exercise methods on frailty in older adults. Outcome assessors were blinded; participants were not.<br>
Results: Here we show the results of the 58 participants. Group sizes are: 3 times/day & everyday (n = 14), 3 times/day & 3 days/week (n = 15), once/day & everyday (n = 14), once/day & 3 days/week (n = 15). The trial is completed as planned, and all randomized participants are analyzed. The main effect of time is significant for the number of frailty criteria (F = 14.803, p < 0.001, partial eta squared = 0.215). The mean changes from baseline to follow-up are −0.357 (95% Confidence Interval −0.787 to 0.073) in the 3 times/day & everyday group, −0.600 (95% Confidence Interval −1.255 to 0.055) in the 3 times/day & 3 days/week group, −0.571 (95% Confidence Interval −1.379 to 0.236) in the once/day & everyday group, and −0.600 (95% Confidence Interval −1.008 to −0.192) in the once/day & 3 days/week group. The main effect of time is also significant for the number of oral hypofunction criteria (F = 16.456, p < 0.001, partial eta squared = 0.234). No important adverse events or side effects related to the intervention were observed.<br>
Conclusions: After conducting oral exercises for 3 months on older adults with pre-frailty or frailty, improvements in frailty are observed. Overall, these exercises could be a simple, low-cost way to support healthy aging in the community.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841812026Saliva as a Reliable and Non-invasive Sample for Detecting Influenza A in Severe Acute Respiratory Infection Casese100872ENJunko STakeuchiDepartment of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health SecurityNobuakiMatsunagaAntimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health SecurityAiTsukadaAntimicrobial Resistance (AMR) Clinical Reference Center, Japan Institute for Health SecurityNorikoIwamotoDisease Control and Prevention Center, Japan Institute for Health SecurityNorikoFuwaDisease Control and Prevention Center, Japan Institute for Health SecurityTakahiroIchikawaDepartment of Infectious Diseases, Sapporo City General HospitalYasuyukiKatoDepartment of Infectious Diseases, International University of Health and Welfare (IUHW) Narita HospitalYukaTomitaDepartment of Infectious Diseases, Japanese Red Cross Aichi Medical Center Nagoya Daini HospitalHirokiKitagawaDepartment of Infectious Diseases, Hiroshima University HospitalMasayaYamatoDepartment of General Internal Medicine and Infectious Diseases, Rinku General Medical CenterTetsujiAoyagiDepartment of Clinical Infectious Diseases, Tohoku University Graduate School of MedicineHideharuHagiyaDepartment of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaHaseDepartment of Infectious Diseases, Japanese Red Cross Narita HospitalShujiHatakeyamaDivision of Infectious Diseases, Jichi Medical University HospitalTohruInabaDepartment of Infection Control and Laboratory Medicine, Kyoto Prefectural University of MedicineKoichiIzumikawaYoshioTakesueDepartment of Infectious Diseases, Nagasaki University Graduate School of Biomedical SciencesMotoKimuraDepartment of Academic-Industrial Partnerships Promotion, Center for Clinical Sciences, Japan Institute for Health SecurityNorioOhmagariDisease Control and Prevention Center, Japan Institute for Health SecurityBackground<br>
Nasopharyngeal swab sampling remains the gold standard for influenza diagnosis; however, it has several limitations, including dependence on medical staff, invasiveness, potential for nosocomial transmission, and occupational exposure risk. Non-invasive alternatives, such as saliva and nasal vestibular swabs, may improve patient comfort and participation in clinical studies. In addition, diagnosis with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) is often delayed because it requires trained laboratory technicians and facilities with appropriate laboratory settings. Although rapid diagnostic devices such as the GenPad® offer potential alternatives to RT-qPCR, their performance with non-invasive samples remains insufficiently explored. This study addresses the two key questions for influenza detection in severe acute respiratory infection (SARI) cases: (i) whether saliva or nasal vestibular swab samples serve as suitable alternatives to nasopharyngeal swab samples, and (ii) whether the GenPad® provides a reliable option for detecting influenza using saliva samples.<br>
Methodology<br>
A prospective observational study was conducted with 16 inpatients classified as having SARIs and diagnosed with influenza between December 2024 and March 2025 in Japan. Paired saliva and nasal vestibular swab samples were collected 1-9 (median = 3.5) days after symptom onset. RT-qPCR testing was performed according to the National Institute of Infectious Diseases protocol. Saliva samples were also tested using the GenPad® system. Comparisons between sample types and diagnostic methods were analyzed using the exact McNemar's test.<br>
Results<br>
Among the 16 influenza-positive patients, saliva samples demonstrated higher sensitivity (87.5%) than nasal vestibular swabs (31.3%) in RT-qPCR when compared with the diagnostic results obtained from nasopharyngeal swabs. A comparison of RT-qPCR results between saliva and nasal vestibular swabs revealed a total agreement of 43.8%, with exact McNemar's test showing a significant difference (p = 0.0039). While nasal vestibular swabs showed inconsistent results, saliva samples consistently tested positive, particularly within seven days of symptom onset (100% positive agreement). The GenPad®, a rapid diagnostic device, showed promising performance (92.9%) using saliva samples compared to RT-qPCR.<br>
Conclusions<br>
Saliva is a reliable non-invasive alternative to nasopharyngeal swabs for influenza detection in SARI cases, particularly within seven days of symptom onset, whereas nasal vestibular swabs show lower sensitivity. Additionally, the GenPad® provides comparable performance to RT-qPCR using saliva samples, offering a rapid, portable diagnostic option. These approaches may mitigate discomfort, minimize infection risk for healthcare workers, and improve testing capacity. However, the absence of influenza-negative controls and the small sample size (n = 16) substantially limit the assessment of diagnostic accuracy and specificity. As a result, the broader applicability of our findings should be interpreted with caution, and further studies are required to validate these observations.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417122025Streptococcal Toxic Shock Syndrome Following Intestinal Obstruction in a Patient With Crohn’s Diseasee100138ENAyanoNishioDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University HospitalToshihiroInokuchiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMikakoIshiguroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukiAoyamaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasahiroTakaharaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSakikoHiraokaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKoheiOguniDepartment of Infectious Diseases, Okayama University HospitalHideharuHagiyaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYutoMatsuokaDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomoyukiKanazawaDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesStreptococcal toxic shock syndrome (STSS) is a rare, life-threatening complication of invasive group A streptococcal (iGAS) infections. We report the case of a 24-year-old woman with Crohn's disease receiving immunosuppressive therapy who developed STSS following intestinal obstruction. On day 2, she developed fever, altered mental status, hypoxemia, erythema, and hypotension. Chest CT revealed bilateral pulmonary infiltrates, and blood cultures grew emm1-positive M1UK Streptococcus pyogenes, confirming STSS. Early multidisciplinary intervention resulted in rapid recovery without sequelae. This case emphasizes the importance of considering iGAS-induced STSS in septic shock, especially in immunocompromised patients, and highlights the need for prompt recognition and treatment.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X8012026Effective Treatment of Advanced Hepatocellular Carcinoma with Extensive Peritoneal Dissemination Using Lenvatinib6974ENShinyaWakatsukiDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterShinyaSakamotoDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterAkikoUenoDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterTakaomiNambaDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterYoritoYamamotoDepartment of Obstetrics and Gynecology, Kochi Health Sciences CenterManabuMatsumotoDepartment of Diagnostic Pathology, Kochi Health Sciences CenterJunIwataDepartment of Diagnostic Pathology, Kochi Health Sciences CenterTakehiroOkabayashiDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterCase Report10.18926/AMO/70075Patients with hepatocellular carcinoma (HCC) and extensive peritoneal dissemination generally have a poor prognosis and are often resistant to systemic therapy. We report the case of a 47-year-old woman with HCC and massive peritoneal dissemination who presented with malignant ascites requiring repeated cell-free and concentrated ascites reinfusion therapy and peritoneovenous shunt placement, as well as malignant pleural effusion requiring pleurodesis. Combined immunotherapy with durvalumab/tremelimumab was initiated;however, disease progression was observed after three treatment courses, prompting a switch to lenvatinib therapy. Two months after initiation of lenvatinib, CT imaging demonstrated complete disappearance of arterial enhancement in the primary hepatic lesion, along with reduction in the size of peritoneal dissemination nodules. Thirteen months after switching to lenvatinib (16 months after the initial diagnosis), the alpha-fetoprotein level continued to decrease, and the disease remained stable under treatment. Despite the extremely high tumor burden, lenvatinib achieved disease stabilization and symptomatic improvement.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1757-47491812026Sodium butyrate augments the antibacterial activity of tetracycline against clinical isolates of multidrug-resistant Vibrio cholerae9ENSushmitaKunduDivision of Biochemistry, ICMR- National Institute for Research in Bacterial InfectionsSourinAluDivision of Biochemistry, ICMR- National Institute for Research in Bacterial InfectionsAbhishekSinghDivision of Biochemistry, ICMR- National Institute for Research in Bacterial InfectionsAnimeshGopeDivision of General Medicine, ICMR- National Institute for Research in Bacterial InfectionsRanjan KumarNandyDivision of Bacteriology, ICMR- National Institute for Research in Bacterial InfectionsAsish K.MukhopadhyayDivision of Bacteriology, ICMR- National Institute for Research in Bacterial InfectionsShin-ichiMiyoshiDivision of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNabendu SekharChatterjeeDivision of Biochemistry, ICMR- National Institute for Research in Bacterial InfectionsSushmitaBhattacharyaDivision of Biochemistry, ICMR- National Institute for Research in Bacterial InfectionsBackground Antibiotic resistance poses a major challenge in treating Vibrio cholerae infections. One promising method to counter resistance is the co-administration of antibiotics with non-antibiotic adjuvants to enhance their efficacy. This study investigated the combined action of sodium butyrate (SB) and tetracycline on tetracycline-resistant V. cholerae strains.<br>
Results The combined activity of SB and antibiotics was assessed on eight V. cholerae clinical isolates using the Fractional Inhibitory Concentration Index (FICI), with SB-Tetracycline showing strong synergy (FICI: 0.09–0.5). Functional and mechanistic studies, including time-kill kinetics, live/dead staining, SEM-based morphological analysis, and fluorometric assays, demonstrated a synergistic antibacterial effect of SB and Tetracycline. This effect was associated with increased membrane permeability, disruption of membrane integrity, dissipation of the proton motive force, and suppression of efflux activity. These changes collectively led to membrane damage, enhanced intracellular accumulation of Tetracycline, decreased intracellular ATP levels, and ultimately, bacterial cell death. Moreover, GM1-CT ELISA and fluorescence microscopy revealed the synergistic anti-virulence activity of the SB- Tetracycline combination. Finally, the combination of SB and Tetracycline showed enhanced efficacy in animal models compared with monotherapy.<br>
Conclusion: The observed SB-Tetracycline synergy provides a promising therapeutic approach to overcome tetracycline resistance in V. cholerae, offering a potential adjunct strategy for the management of antibiotic-resistant cholera infections.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1862-40652026Does Human Depopulation Reduce Resource Consumption? Evidence from Anthropocene JapanENAnassBarrahmouneGraduate School of Humanities and Social Sciences, Faculty of Economics, Okayama UniversityPeterMatanleSchool of East Asian Studies, The University of SheffieldJiyoungKimGraduate School of Humanities and Social Sciences, Faculty of Economics, Okayama UniversityHumanity’s deepening strain on Earth systems has sparked widespread discussion of an “Anthropocene crisis,” often attributed to overpopulation. This raises the question: if overpopulation underpins the crisis, does its resolution lie in depopulation? Here, we examine the effects of Japan’s ongoing depopulation on the nexus of population, economy, cropland use, food, water, and energy. We take a systematic Bayesian approach to examine changes in the strength and direction of causality among these variables and explore plausible future pathways under Shared Socioeconomic Pathway (SSP) scenarios. We find that, while depopulation has led to reductions in resource demand, notably for water and energy, impacts on the food system are more complex due to interdependencies with economic and other factors beyond population change. In conclusion, we argue that it will take longer than predicted for depopulation dividends to materialize at a scale that could meaningfully contribute to addressing the crisis, and that proactive efforts to reshape consumption patterns and restructure economic systems, from a model predicated on perpetual growth to one oriented toward sufficiency, are necessary to capitalize on the potential dividends offered by this demographic shift.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1349-41475412026Mycobacterium mageritense-associated refractory cutaneous infection and lymphadenitis in an immunocompetent adult: insights from genomic sequencing19ENShinnosukeFukushimaDepartment of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineJumpeiUchiyamaDepartment of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYoshioKawakamiDepartment of Dermatology, Okayama University HospitalYoshikoMatsuuraKonohana Dermatology ClinicSatoruSugiharaDepartment of Dermatology, Okayama University HospitalShinMorizaneDepartment of Dermatology, Okayama University HospitalPoowadonMuenrayaDepartment of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalBackground Nontuberculous mycobacteria are increasingly recognized as causes of chronic and refractory skin and soft tissue infections, even in individuals without immunodeficiency. Among them, Mycobacterium mageritense is a rare, rapidly growing species that can lead to persistent lesions requiring prolonged antimicrobial therapy. Reports of M. mageritense infections involving both the skin and regional lymph nodes are limited, and this case adds new clinical and genomic insights.<br>
Case presentation A 48-year-old previously healthy man presented with a slowly enlarging cutaneous lesion on his lower leg and ipsilateral inguinal lymphadenitis. Empirical antibacterial therapy with β-lactams and macrolides was ineffective. Wound cultures subsequently grew M. mageritense, confirmed by whole-genome sequencing. Several antimicrobial regimens were attempted, and the final successful therapy consisted of oral levofloxacin and minocycline for 4 months, leading to complete clinical resolution. Genomic analysis identified resistance-related genes, including erm(40), aac(2′)-Ib, tet(V), and RbpA, although in vitro minimum inhibitory concentrations showed variable susceptibility. Phylogenetic comparison revealed that the isolate was closely related to previously reported M. mageritense strains from Japan.<br>
Conclusions This case demonstrates that M. mageritense can cause cutaneous infection with secondary lymphadenitis in an immunocompetent host. Accurate species identification using molecular or genomic methods and selection of appropriate combination antibiotic therapy based on susceptibility testing are crucial for successful management of such infections.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841732025Prospective Evaluation of the Safety and Compression Performance of Novel Compression Denim Jeans in Healthy Volunteers and Patients With Lymphedemae80971ENDaikiOusakaDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKiyoshiYamadaDepartments of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNorikoSakanoDepartment of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoeKirinoDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazumasaMiyakeDepartment of Rehabilitation, Lymphedema Treatment Center, Kousei HospitalTakumiTakahashiDivision of Business Management, Matsuoka CorporationAkihiroMatsuokaDivision of Production Engineering, Matsuoka CorporationShintaroYamadaDivision of Sales, Kaihara CorporationAkiraShinaokaDepartment of Lymphatics and Edematology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSusumuOozawaDepartment of Clinical Safety, Okayama University HospitalObjectives: The treatment of lower-extremity lymphedema, whether congenital or acquired, remains challenging. Long-term management aimed at reducing complications and maximizing quality of life is essential. Compression stockings are crucial in this management; however, their application is limited by patient experience (ease of wear, texture, breathability, and appearance). This highlights the need to evaluate alternative compression garments that maintain therapeutic efficacy while improving patient adherence.<br>
Methods: We developed a novel compression denim product (Flow plus Jeans®) using advanced sewing technology. Its baseline performance (compression ability) was evaluated by measuring pressure gradients at three points (ankle, calf, and thigh) using a mannequin-based compression testing system and compared with those of existing stockings. Thereafter, a safety assessment was conducted on healthy volunteers to evaluate potential adverse effects, including changes in lower limb circumference, signs of deep vein thrombosis (DVT) via ultrasound, and skin complications. A clinical trial in patients with lymphedema was then performed to compare its efficacy with that of conventional compression stockings.<br>
Results: Baseline performance testing with a mannequin revealed that Flow plus Jeans demonstrated compression levels and pressure gradients at three calf points comparable to those of standard compression stockings. A safety study involving nine healthy volunteers confirmed that Flow plus Jeans caused no significant changes in lower-limb circumferences after three days of wear, with no cases of DVT or skin complications. In a subsequent clinical trial involving nine female patients with lymphedema, the jeans showed non-inferiority to existing stockings concerning lower-limb circumference measurements at six points (pre-use vs. six months post-use), with patient-reported experiences assessed via questionnaires. Notably, patients reported enhanced satisfaction regarding the jeans' fashionability, which could serve as an incentive for long-term adherence.<br>
Conclusion: Our findings suggest that Flow plus Jeans represent a promising novel option for the long-term management of lymphedema, offering an alternative that balances medical efficiency with improved patient satisfaction and demonstrates safety in healthy individuals.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2059-36351112026Osimertinib inhibits the MYLK4-mediated phosphorylation of CDKAL1 to suppress stemness and chemoresistance in rhabdomyosarcoma26ENTakutoItanoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRongshengHuangDepartment of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEijiNakataDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsushiFujimuraDepartment of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841812026Central Serous Chorioretinopathy in Parallel With Onset and Relapses of Minimal Change Nephrotic Syndrome: A 28-Year Case Follow-Upe102426ENToshihikoMatsuoDepartment of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology, and Metabolism, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityCentral serous chorioretinopathy is an idiopathic disease that manifests as one or several localized, small, dome-shaped serous retinal detachments on fundus examination. The pathophysiology involves fluid leakage from the choroidal capillaries, known as the choriocapillaris, into the subretinal space through sites of damage in the retinal pigment epithelium. This case report discusses the underlying causes of central serous chorioretinopathy-like findings in minimal change nephrotic syndrome.<br>
<br>
The patient was a 33-year-old woman who developed nephrotic syndrome that was confirmed to be minimal change disease by renal biopsy. She experienced two major relapses of nephrotic syndrome at the ages of 36 and 41 years. She also had a minor relapse at the age of 37 years, five months after the first major relapse at the age of 36 years, as well as four additional minor relapses at the ages of 44, 46, 50, and 51 years. The onset of central serous chorioretinopathy-like manifestations, which were localized to the left eye, occurred three months after the initial onset of nephrotic syndrome at the age of 33 years. Two subsequent episodes of relapse of central serous chorioretinopathy-like manifestations were observed in both eyes at intervals of five months and one month, respectively, after major relapses of nephrotic syndrome at the ages of 36 and 41 years. Thereafter, she did not develop further central serous chorioretinopathy-like manifestations.<br>
<br>
She discontinued oral prednisolone at the age of 54 years and experienced no further relapses of nephrotic syndrome through her latest visit at the age of 61 years. She maintained normal renal function and good visual acuity in both eyes. The long-term, consistent temporal association between episodes of central serous chorioretinopathy and the onset and relapses of minimal change nephrotic syndrome is strongly supported by longitudinal clinical observations spanning 28 years. This parallel course suggests a possible shared pathophysiological mechanism or common triggering factors underlying both diseases.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612025Salivary short chain fatty acids serve as biomarkers of periodontal inflammatory burden1786ENKazuTakeuchi-HatanakaDivision of Periodontics and Endodontics, Department of Dentistry, Okayama University HospitalYasushiShirahaseSysmex CorporationToshiyukiYoshidaSysmex CorporationMariKonoSysmex CorporationNaokiToyaSysmex CorporationKenjiKonishiPresent address: Diagnostics Division, IVD Enzyme Department, Nagase DiagnosticsKazuhiroOmoriDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPeriodontitis is a chronic inflammatory condition associated with systemic diseases. Early detection and intervention are crucial; however, conventional diagnostic methods require specialized dental procedures. Therefore, we aimed to develop a noninvasive saliva-based screening method that can be easily performed outside dental clinics. This cross-sectional pilot study evaluated three periodontal indices—probing depth, Periodontal Inflamed Surface Area (PISA), and periodontal epithelial surface area—in relation to short-chain fatty acids (SCFAs) and bacterial profiles in the saliva. Saliva samples collected during the day exhibited stronger correlations with periodontal indices than waking time samples, demonstrating a significant association with periodontal pathogens, protease activity, and elevated levels of butyric acid. The diagnostic thresholds for PISA were 300 mm2 and 600 mm2. Multivariate logistic regression and likelihood ratio analyses identified the combination of enzymatic SCFA markers and dipstick-based occult blood or leukocyte detection as a promising biomarker pair. Combining enzymatic SCFA markers with occult blood demonstrated a positive likelihood ratio of 3.4 and a negative likelihood ratio of 0.19 for PISA ≥ 600 mm2, with a post-test probability of 77%, sensitivity of 86%, and specificity of 75%. These findings suggest that combining salivary enzymatic and dipstick-based biomarkers provides a simple, cost-effective, and moderately informative screening strategy for periodontitis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841812026Endoscopic Topical Application (ETA) Therapy for Refractory Overactive Bladder: A First-in-Human Reporte101143ENTakuyaSadahiraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroSugiharaDepartment of Surgery, Nishi Fukuyama HospitalYosukeMitsuiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToyohikoWatanabeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasamiWatanabeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRefractory overactive bladder (OAB) remains a clinical challenge despite established therapies, such as anticholinergics, β3-agonists, and intradetrusor botulinum toxin (BTX). Emerging evidence suggests that sensory mechanisms within the bladder, including those involving the trigone where superficial afferent networks are present, may contribute to persistent urinary urgency and frequency in some patients. Although intradetrusor BTX injection is effective in selected patients, its impact on these superficial pathways may be limited because the injected drug predominantly distributes within the detrusor. Endoscopic topical application (ETA) therapy delivers BTX directly to the trigone under air cystoscopy, potentially providing targeted modulation of sensory hyperexcitability. We report a 72-year-old woman with long-standing refractory OAB who experienced only partial improvement with repeated intradetrusor BTX injections but achieved clinically meaningful symptom relief after ETA therapy. Nocturia, urgency, urgency urinary incontinence, and voided volume were improved, with no complications other than transient postoperative urethral pain. This case suggests that ETA therapy may represent a promising sensory-focused option for refractory OAB.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Single cell spatial transcriptomics links Wnt signaling disruption to extracellular matrix development in a cleft palate model29639ENJeremie OliverPiñaSection on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)ResmiRajuSection on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)EvanStipanoSection on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)Aye ChanMyoSection on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)ZiyiWangGraduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama UniversityMitsuakiOnoGraduate School of Medicine Dentistry and Pharmaceutical Sciences, Department of Molecular Biology and Biochemistry, Okayama UniversityParnaChattarajSection on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)MasaeFurukawaSection on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)Rena N.D’SouzaSection on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)Despite advances in understanding the morphological disruptions that lead to defects in palate formation, the precise perturbations within the signaling microenvironment of palatal clefts remain poorly understood. To explore in greater depth the genomic basis of palatal clefts, we designed and implemented the first single cell spatial RNA-sequencing study in a cleft palate model, utilizing the Pax9−/− murine model at multiple developmental timepoints, which exhibits a consistent cleft palate defect. Visium HD, an emerging platform for true single-cell resolution spatially resolved transcriptomics, was employed using custom bins of 2 × 2 μm spatial gene expression data. Validation of spatial gene expression was then validated using custom designed Xenium In Situ mRNA spatial profiling and RNAscope Multiplex assays. Functional enrichment analysis revealed a palate cell-specific perturbation in Wnt signaling effector function in tandem with disrupted expression of extracellular matrix genes in developing mesenchyme. As a key step toward laying the framework for identifying key molecular targets these data can be used for translational studies aimed at developing effective therapies for human palatal clefts.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417112025Perioperative Multidisciplinary Intervention Led to Complete Minimally Invasive Transthoracic Esophagectomy for a Patient With Severe Lung Dysfunction: A Case Reporte97931ENMakotoMatsumotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasashiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKentoKawasakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomoyoshiKunitomoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNaoakiMaedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRisk factors for postoperative pneumonia after esophagectomy include smoking, severe lung dysfunction, and sarcopenia. Heavy smokers often have chronic obstructive pulmonary disease (COPD), which is associated with poor physical activity and low muscle strength. Sarcopenia is also associated with decreased physical function and malnutrition. These factors lead to a close relationship between COPD and sarcopenia. This report describes the case of a 74-year-old man who presented with dysphagia and was diagnosed with advanced esophageal cancer with lymph node metastasis. Preoperative respiratory function testing showed a forced expiratory volume in one second (FEV1) of 0.76 L because of his past smoking and COPD. Multidisciplinary intervention was started, along with neoadjuvant chemotherapy. Preoperative management improved his physical function. Robot-assisted thoracoscopic subtotal esophagectomy with the patient in the prone position was performed with curative resection and no severe postoperative complications. The perioperative multidisciplinary intervention improved physical functions and enabled safe robot-assisted thoracoscopic esophagectomy for the patient with severe lung dysfunction in the prone position. This case highlights that not only respiratory status but also physical parameters should be taken into account when considering whether a patient can tolerate surgery safely.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2366-10701342025Asian Subgroup Analysis of Patients in the Phase 2 DeLLphi-301 Study of Tarlatamab for Previously Treated Small Cell Lung Cancer10411054ENMyung-JuAhnHematology-Oncology Department, Samsung Medical Center (SMC), Sungkyunkwan University School of MedicineByoung ChulChoMedical Oncology Department-501, ABMRC, Yonsei UniversityKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalHirokiIzumiThoracic Oncology, National Cancer Center Hospital EastJong-SeokLeeHematology/Oncology, Seoul National University Bundang HospitalJi-YounHanCenter for Lung Cancer, National Cancer Center-Graduate School of Cancer Science and PolicyChi-LuChiangDepartment of Chest Medicine, Taipei Veterans General HospitalShuangHuangAmgen Inc.AliHamidiAmgen Inc.SujoyMukherjeeAmgen Inc.Krista LinXuAmgen Asia Pacific Pte. Ltd.HiraokiAkamatsuInternal Medicine III, Wakayama Medical UniversityIntroduction: Tarlatamab is a bispecific T-cell engager (BiTE®) immunotherapy that binds delta-like ligand 3 on the surface of small cell lung cancer (SCLC) cells and CD3 on T cells, facilitating T cell-mediated cancer cell lysis. In the primary analysis of the phase 2 DeLLphi-301 study (NCT05060016), tarlatamab showed a favourable benefit-to-risk profile with durable objective responses and promising survival outcomes in patients with previously treated SCLC. Here, phase 2 data for the Asia region subgroup are presented.<br>
Methods: Patients with previously treated, advanced SCLC received 10 mg tarlatamab every 2 weeks. The primary endpoint was objective response rate (ORR) by blinded independent central review (RECIST version 1.1). Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. The present analysis includes patients enrolled at sites in Asia.<br>
Results: A total of 43 patients were enrolled at sites in Asia. ORR was 46.3% (95% confidence interval [CI], 30.7–62.6) and median DOR was 7.2 months (95% CI 3.9 to not estimable). The median follow-up was 16.6 months for PFS and 21.2 months for OS. Median PFS was 5.4 months (95% CI 3.0–8.1) and median OS was 19.0 months (95% CI 11.4 to not estimable). The most common treatment-emergent adverse event (AE) was cytokine release syndrome (48.8%), and all such events were grade 1 or 2. There were no discontinuations due to treatment-related AEs.<br>
Conclusions: Tarlatamab demonstrated durable responses and promising survival outcomes with a manageable safety profile in this post hoc analysis of patients from Asia with previously treated SCLC.<br>
Trial Registration: ClinicalTrials.gov, NCT05060016.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0300-81262025Hospital-acquired pneumonia caused by multidrug-resistant Streptococcus pneumoniae serotype 15AENHidemasaAkazawaDepartment of Infectious Diseases, Okayama University HospitalShinnosukeFukushimaDepartment of Infectious Diseases, Okayama University HospitalKentaNakamotoDepartment of Infectious Diseases, Okayama University HospitalKoheiOguniDepartment of Infectious Diseases, Okayama University HospitalMadokaShimbeDepartment of Infectious Diseases, Okayama University HospitalBinChangDepartment of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health SecurityYukihiroAkedaDepartment of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health SecurityHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalBackground Streptococcus pneumoniae remains a common cause of community-acquired pneumonia but is an infrequent pathogen in hospital-acquired pneumonia (HAP). Non-vaccine serotypes of multidrug-resistant (MDR) S. pneumoniae strains have been emerging globally, posing an increased risk of nosocomial infection.<br>
Case A 71 year-old man developed pneumonia on postoperative day 4 following spinal fusion surgery. Despite initial treatment with ampicillin/sulbactam, his condition deteriorated, requiring ICU admission and mechanical ventilation. Microbiological testing confirmed S. pneumoniae as a causative pathogen, and ceftriaxone was empirically administered based on the local antibiogram. However, antimicrobial susceptibility testing revealed resistant profiles to penicillin (minimum inhibitory concentration [MIC], 8 µg/mL), ceftriaxone (MIC, 16 µg/mL), meropenem (MIC, 1 µg/mL), macrolides, and clindamycin, while demonstrating susceptibility to levofloxacin and vancomycin. The therapeutic regimen was subsequently adjusted to levofloxacin, resulting in clinical improvement. The isolate was later identified as serotype 15A, sequence type 63 (ST63).<br>
Conclusion This case highlights that MDR S. pneumoniae can cause early-onset HAP and may not be covered by standard empiric therapies, emphasizing the need for careful evaluation of treatment response. Continued surveillance of infections caused by vaccine-escape clones like MDR serotype 15A is essential, given their increasing clinical relevance.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0301-486X19062025Prognostic Value of Serum (1→3)-β-D-Glucan Levels in Patients with Candidemia Stratified by Compliance with Candida Bundle: A Multicenter Retrospective Cohort Study (2016–2023)90ENHidemasaAkazawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinnosukeFukushimaDepartment of Infectious Diseases, Okayama University HospitalToshieHiguchiDepartment of General Internal Medicine, Okayama Red Cross HospitalTomokoMiyoshiCenter for Medical Education and Internationalization, Kyoto University Graduate School of MedicineYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalYukinobuAkamatsuDepartment of General Medicine, Tottori Municipal HospitalYutoHarukiDepartment of Pharmacy, Tsuyama Chuo HospitalYoshitakaIwamotoDepartment of General Medicine, NHO Okayama Medical CenterShuichiTanakaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunFujisatoDepartment of Pharmacy, Okayama Rousai HospitalSoichiroAkoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalBackground Candidemia is a severe systemic infection with a high mortality risk. While β-D-glucan (BDG) serves as a diagnostic biomarker, its prognostic value in candidemia, particularly in association with Candida bundle compliance, remains unclear.<br>
Methods In this retrospective multicenter cohort study, we evaluated 96 patients with candidemia across nine Japanese hospitals between 2016 and 2023. Candida bundle compliance was assessed using five key components: central venous catheter removal within 24 h of diagnosis, appropriate initial antifungal therapy, ophthalmologic examination, follow-up blood cultures until clearance, and antifungal therapy for at least two weeks post-clearance. Analyses stratified patients by serum BDG status (positive/negative) and compliance with the Candida bundle (high: 4–5 points; low: 0–3 points). The primary outcome was 30-day mortality, and the secondary outcome was defined as endophthalmitis incidence.<br>
Results Of 96 eligible patients with candidemia, 70 (72.9%) were BDG-positive and 26 (27.1%) were BDG-negative. The overall 30-day mortality was 17.7%. Among BDG-positive patients, 15 (21.4%) died, while 2 (7.7%) died in BDG-negative cohorts (p = 0.09). Serum BDG positivity demonstrated a statistically significant association with decreased survival rates in the low bundle adherence group (p = 0.02), whereas this correlation was not observed among patients in the high-compliance cohort (p = 0.66). Endophthalmitis occurred in 25.0% of patients, without significant correlation to serum BDG status. C. albicans was associated with a significantly higher incidence of endophthalmitis compared with non-albicans species (45.7% vs. 8.9%).<br>
Conclusions Serum BDG positivity potentially correlates with worse survival in candidemia, particularly in patients with low bundle compliance. This emphasizes the importance of adherence to standardized Candida management protocols for optimizing patient outcomes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0925-571012252025Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial733743ENNorikoDokiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalShinichiKakoDivision of Hematology, Jichi Medical University Saitama Medical CenterEmikoSakaidaDepartment of Hematology, Chiba University HospitalYoshinobuKandaDivision of Hematology, Department of Medicine, Jichi Medical UniversityIdiopathic pneumonia syndrome (IPS) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a poor prognosis. Although IPS is often treated with steroids, the disease can become resistant to or dependent on steroid treatment, and there is no effective cure for patients with refractory or steroid-dependent IPS. This multicenter, open-label, single-arm, phase II clinical trial investigated the efficacy and safety of HLC-001 (allogeneic umbilical cord-derived mesenchymal stromal cells) in patients with progressive steroid-dependent or refractory IPS after HSCT. Seven male patients (all male; mean age: 43.3 years) received HLC-001 and three completed the trial. The survival rate at day 56 (primary endpoint) was 71.4% (5/7 patients; 95% confidence interval: 29.0%–96.3%) and was sustained at day 100, suggesting that HLC-001 was more effective than previously reported treatment. Three of the five patients with ≥ 100 days of follow-up died. Five patients experienced at least one adverse drug reaction, none of which were serious. These findings indicate that HLC-001 was potentially effective and generally well tolerated in Japanese patients with steroid-dependent or refractory IPS after HSCT. Given there is no effective cure for steroid-dependent or refractory IPS, HLC-001 may be a promising treatment option and further clinical evaluation is warranted.<br>
Trial registration: Japan Registry of Clinical Trials identifier: jRCT2063220014.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1340-68683262025Clinical significance on switching CDK4/6 inhibitors among 13,284 patients with metastatic breast cancer14051416ENTakuyaNishinaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMakiTaniokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKenjiTakadaMedical AI Project, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakahiroTsukiokiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYukoTakahashiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTadahikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityRecent clinical trials have shown that switching to a combination therapy of a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) prolongs progression-free survival (PFS) compared with ET monotherapy. Reports indicate that abemaciclib provides benefits regardless of the PIK3CA mutation status; however, its clinical benefits remain insufficient. This study aimed to evaluate the clinical significance of switching CDK4/6i + ET in a large real-world cohort. Using a medical database, we identified 13,284 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who received CDK4/6i + ET between 2008 and 2022. Patients were categorized into five groups based on their first- and second-line therapy patterns. We compared the median time to discontinuation (TTD) among the groups. In patients who switched from one CDK4/6i + ET to another CDK4/6i + ET, the second-line TTD and total TTD of first- and second-line therapies (n = 542) were significantly longer than those in patients who switched from CDK4/6i + ET to ET monotherapy (n = 490) (the second-line TTD: 11.2 vs. 4.9 months, p < 0.01; total TTD: 25.1 vs. 20.5 months, p < 0.01). The order of palbociclib and abemaciclib administration did not significantly affect the second-line or total TTD in patients who switched from one CDK4/6i + ET to another CDK4/6i + ET. Switching from one CDK4/6i + ET to another CDK4/6i + ET resulted in a significantly longer TTD than switching to ET monotherapy. Considering the phase III clinical trial results of capivasertib, switching to CDK4/6i + ET is a viable therapeutic option regardless of the PIK3CA mutation status.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-08517512025Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING10ENMasakiSakamotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTetsuyaKatayamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuMikaneDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunyaHanzawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeKadowakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiHamadaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyomaSugimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChiakiYagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuoUrataOncolys BioPharma, Inc.ToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe gut microbiota plays an essential role in regulating host immunity, and its metabolites such as butyrate exert immunomodulatory effects by acting as histone deacetylase inhibitors. Oncolytic virotherapy has emerged as a promising approach for cancer treatment, and we have developed OBP-702, a telomerase-specific oncolytic adenovirus that expresses p53 and elicits strong systemic antitumor responses. In this study, the potential synergy between butyrate and OBP-702 was investigated in colorectal cancer models. Using human and murine colorectal carcinoma cell lines, butyrate was found to directly enhance the infectivity of OBP-702 by upregulating CAR and integrins, thereby promoting apoptosis and autophagy in tumor cells. In addition, butyrate indirectly boosted systemic antitumor immunity by upregulating MHC-I expression through activation of the cGAS-STING pathway and enhancing CD8 + T cell recruitment via CXCL10 secretion. These findings were supported by in vivo experiments using CT26 subcutaneous, bilateral, and orthotopic tumor models, in which the combination of oral butyrate and intratumoral OBP-702 administration produced synergistic antitumor effects. These results highlight the therapeutic potential of integrating gut microbial metabolites with oncolytic virotherapy as a novel immunotherapeutic strategy for colorectal cancer.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0312-596364122025Evaluation of Fentanyl-Emerged Adverse Events and Pharmacokinetics in Neonates: A Physiologically Based Pharmacokinetic Modeling Approach18111825ENWalaa Yousef BassyouniMahdyDepartment of Pharmacy, Kobe University HospitalKazuhiroYamamotoDepartment of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRisaJojiDepartment of Pharmacy, Kobe University HospitalMariHashimotoDepartment of Pharmacy, Kobe University HospitalRukaNakasoneDepartment of Pediatrics, Graduate School of Medicine, Kobe UniversityKazumichiFujiokaDepartment of Pediatrics, Graduate School of Medicine, Kobe UniversityKotaroItoharaDepartment of Pharmacy, Kobe University HospitalYumiKitahiroDepartment of Pharmacy, Kobe University HospitalTomohiroOmuraDepartment of Pharmacy, Kobe University HospitalIkukoYanoDepartment of Pharmacy, Kobe University HospitalBackground Despite its common use for analgesia in neonatal intensive care units, the optimal dosing and safety profile of fentanyl, particularly regarding suspected fentanyl-emerged adverse events (FEAEs), such as hypotension, desaturation, and oliguria, are not well-defined.<br>
Objective This study aimed to develop an optimal therapeutic monitoring and dosing strategy for fentanyl for neonates. A physiologically based pharmacokinetic (PBPK) model for predicting fentanyl pharmacokinetics across various populations, including preterm and term neonates, was developed, and the relationship between predicted fentanyl exposure and FEAE incidence in neonates was assessed.<br>
Methods A PBPK model was developed and validated against the observed values in the literature. The model’s predictive accuracy for fentanyl pharmacokinetics and association with FEAE incidence in an external retrospective cohort of Japanese neonates was evaluated using the predicted concentrations and pharmacokinetic parameters estimated by PBPK simulation.<br>
Results The PBPK model exhibited reasonable predictive performance for serum fentanyl concentrations in actual neonatal patients (mean error: 9.27% [standard error: 5.06%], root mean squared error: 54.7%). The incidence of any FEAE, particularly oxygen desaturation, was associated with the fentanyl concentration-to-dose ratio, but not with some exposure parameters, such as the area under the curve and maximum concentration. The recommended reduced infusion rate allowed serum fentanyl concentrations to fall within the ranges established by the reported values and our data.<br>
Conclusions Our PBPK model and proposed dosing strategy may contribute to safer and more effective fentanyl use in neonates.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0718-95082025Suppression of Na+ Uptake Via Apoplastic Flow by Chitosan in RiceENMaoxiangZhaoGraduate School of Environmental and Life Science, Okayama UniversityMd. Asadulla AlGalibGraduate School of Environmental and Life Science, Okayama UniversityToshiyukiNakamuraGraduate School of Environmental and Life Science, Okayama UniversityYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityYoshihikoHiraiGraduate School of Environmental and Life Science, Okayama UniversityYoshitakaNakashimaShintaroMunemasaGraduate School of Environmental and Life Science, Okayama UniversityIzumi C.MoriInstitute of Plant Science and Resources, Okayama UniversityYoshiyukiMurataGraduate School of Environmental and Life Science, Okayama UniversityPurpose: Chitosan enhances tolerance to salinity in rice. Apoplastic flow plays a crucial role in the accumulation of sodium (Na+) in rice under salinity. This study investigated the effects of exogenous chitosan on apoplastic flow and Na+ uptake in NaCl-treated rice seedlings. Methods: We employed an apoplastic tracer, trisodium salt of 8-hydroxy-1,3,6-pyrenetrisulphonic acid (PTS), in order to evaluate apoplastic flow in rice (Oryza sativa L., cv. Nipponbare) seedlings that were hydroponically grown in the solution containing NaCl (0 and 25 mM), and chitosan (0 mg L− 1, 10 mg L− 1, and 50 mg L− 1). Results: Application of 25 mM NaCl significantly increased PTS uptake and Na+ content in shoots but did not affect K+ content, resulting in a lower K+/Na+ ratio although 25 mM NaCl did not affect the seedling growth. The application of chitosan suppressed Na+-enhanced PTS uptake and Na+ accumulation in shoots without affecting the K+ content, which led to a higher K+/Na+ ratio. Moreover, chitosan did not affect the reducing sugar content or electrical conductivity in the solution containing NaCl. Conclusions: These results suggest that application of chitosan suppressed Na+-enhanced apoplastic flow to reduce Na+ uptake in rice seedlings.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1472-68312512025Evaluation of Streptococcus mutans strains possessing genes encoding collagen-binding proteins in the Japanese population1908ENMakotoOkudaDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaYutoSuehiroDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaJinthanaLapirattanakulDepartment of Oral Microbiology, Faculty of Dentistry, Mahidol UniversityShuheiNakaDepartment of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMichiyoMatsumoto-NakanoDepartment of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaNomuraDepartment of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityRenaOkawaDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaKazuhikoNakanoDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaBackground Streptococcus mutans harbors collagen-binding protein genes, namely cnm and cbm, which are implicated in its virulence and pathogenicity in both oral and extraoral infections. Although both genes were initially identified in S. mutans isolated from Japanese populations, their geographical prevalence, distribution, and genetic relatedness within Japan remain largely unexplored. This study investigates the prevalence of S. mutans strains carrying cnm and cbm genes across Japan, correlates these findings with clinical data, and analyzes the genetic relatedness of cnm-positive and cnm-negative strains using multilocus sequence typing (MLST).<br>
Methods Dental plaque specimens were collected from 1248 individuals from eight Japanese cities (Hiroshima, Fukuoka, Nagasaki, Niigata, Okayama, Osaka, Tokushima, and Tokyo) and plated on selective medium for S. mutans isolation. S. mutans was confirmed in 523 subjects by colony morphology and PCR using species-specific primers, and the presence of the cnm and cbm genes was determined by PCR with gene-specific primers. Demographic (age, sex) and oral examination (caries prevalence, caries experience, number of teeth) data were recorded. MLST was employed to genotype selected cnm-positive and cnm-negative S. mutans strains to assess their clonal relationships.<br>
Results Among 523 subjects possessing S. mutans (aged 3–90 years), we detected cnm-positive strains in all cities; specifically, the prevalence ranged from 5.5% in Okayama to 25.0% in Tokushima. In contrast, cbm-positive strains were less common and undetectable in some regions. Furthermore, subjects harboring cnm-positive S. mutans were significantly older (p = 0.002) and had higher caries prevalence and experience (p < 0.001). MLST revealed evolutionary relationships among cnm-positive strains across the cities but no discernible region-specific clustering. Clonal relationships partially reflected cnm gene distribution, particularly for exclusively cnm-positive or cnm-negative clonal complexes, but inconsistencies involving serotypes and cnm presence within some clonal complexes and sequence types were also noted.<br>
Conclusions The cnm-positive S. mutans strains are widely distributed throughout Japan and are associated with increased age and caries burden. Although core genome analysis revealed some clonal patterns, the non-uniform distribution of the non-core cnm gene is likely influenced by horizontal gene transfer, providing S. mutans with adaptive advantages irrespective of its core genetic background or serotype.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0006-29282025German Chamomile (Matricaria chamomilla) Induces Cytochrome P450 Expression Through Increased BMAL1 Protein Expression in Liver NucleiENMokaIkedaDivision of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City UniversityYuyaTsurudomeDivision of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City UniversityMaiEnrinDivision of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City UniversityYukiyoWadaDivision of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City UniversityMichikoHoriguchiDepartment of Regenerative and Therapeutic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKentaroUshijimaDivision of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City UniversityGerman chamomile (Matricaria chamomilla) is a medicinal herb that promotes improved digestion and reduces insomnia. Although it is widely used worldwide, the mechanism of induction of drug-metabolizing enzymes is unknown. We found that German chamomile extracts induced cytochrome P450 expression at the transcriptional stage. Cyp3a11 expression is decreased at night in wild-type mice, but German chamomile extract induced nocturnal Cyp3a11 and Cyp1a2 expression. German chamomile extract increased the nuclear protein expression of the clock gene BMAL1, which drives and abolishes the rhythm of Cyp3a11 expression. By contrast, German chamomile extract did not significantly alter clock gene expression in the suprachiasmatic nucleus (SCN). Similarly, it did not affect the mRNA expression of the clock genes in the kidneys. Because it did not induce the mRNA expression of ATP-binding cassette (ABC) transporters (Abcb1a, Abcc2, Abcc4, and Abcg2) in the kidney, German chamomile extract had no effect on the transcription of pharmacokinetics-related molecules other than CYPs. German chamomile extract promoted liver-selective nuclear transfer rhythm changes in clock genes and induced the expression of CYPs. This study may help to explain the mechanism of drug interactions associated with chronic German chamomile extract consumption.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2399-3642812025A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS1720ENRyoichiNakamuraDepartment of Neurology, Aichi Medical University School of MedicineGenkiTohnaiDivision of ALS Research, Aichi Medical University School of MedicineNaokiAtsutaDepartment of Neurology, Aichi Medical University School of MedicineYumiMatsudaPublic Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of MedicineSatoruMorimotoKeio University Regenerative Medicine Research Center, KawasakiDaisukeItoDepartment of Neurology, Nagoya University Graduate School of MedicineMasahisaKatsunoDepartment of Neurology, Nagoya University Graduate School of MedicineYuishinIzumiDepartment of Neurology, Tokushima University Graduate School of Biomedical SciencesMitsuyaMoritaDivision of Neurology, Department of Internal Medicine, Jichi Medical UniversityIkukoIwataDepartment of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityIchiroYabeDepartment of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido UniversityTomokoNakazatoDepartment of Neurology, Juntendo University School of MedicineNobutakaHattoriDepartment of Neurology, Juntendo University School of MedicineTakehisaHirayamaDepartment of Neurology, Toho University Faculty of MedicineOsamuKanoDepartment of Neurology, Toho University Faculty of MedicineAsakoTamuraDepartment of Neurology, Mie University Graduate School of MedicineNaokiSuzukiDepartment of Neurology, Tohoku University Graduate School of MedicineMasashiAokiDepartment of Neurology, Tohoku University Graduate School of MedicineKazumotoShibuyaDepartment of Neurology, Graduate School of Medicine, Chiba UniversitySatoshiKuwabaraDepartment of Neurology, Graduate School of Medicine, Chiba UniversityMasayaOdaDepartment of Neurology, Vihara Hananosato HospitalRinaHashimotoDepartment of Neurology, NHO Higashinagoya National HospitalIkukoAibaDepartment of Neurology, NHO Higashinagoya National HospitalTomohikoIshiharaDepartment of Neurology, Brain Research Institute, Niigata UniversityOsamuOnoderaDepartment of Neurology, Brain Research Institute, Niigata UniversityToruYamashitaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiIshiuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKotaBokudaDepartment of Neurology, Tokyo Metropolitan Neurological HospitalToshioShimizuDepartment of Neurology, Tokyo Metropolitan Neurological HospitalYoshioIkedaDepartment of Neurology, Gunma University Graduate School of MedicineKazukoHasegawaDivision of Neurology, NHO Sagamihara National HospitalFumiakiTanakaDepartment of Neurology and Stroke Medicine, Yokohama City University Graduate School of MedicineTakanoriYokotaDepartment of Neurology and Neurological Science, NucleoTIDE and PepTIDE Drug Discovery Center (TIDE), Institute of Science TokyoKazuakiKanaiDepartment of Neurology, Fukushima Medical University School of MedicineYu-ichiNotoDepartment of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineRyujiKajiDepartment of Neurology, Tokushima University Graduate School of Biomedical SciencesHirohisaWatanabeDepartment of Neurology, Fujita Health UniversityTomokoKonishiDivision of ALS Research, Aichi Medical University School of MedicineMikikoHasegawaDivision of ALS Research, Aichi Medical University School of MedicineHozukiFukayaDivision of ALS Research, Aichi Medical University School of MedicineJun-ichiNiwaDepartment of Neurology, Aichi Medical University School of MedicineManabuDoyuDepartment of Neurology, Aichi Medical University School of MedicineYoheiOkadaDepartment of Neurology, Aichi Medical University School of MedicineShihoNakamuraKeio University Regenerative Medicine Research Center, KawasakiFumikoOzawaKeio University Regenerative Medicine Research Center, KawasakiHideyukiOkanoKeio University Regenerative Medicine Research Center, KawasakiMasahiroNakatochiPublic Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of MedicineGenSobueDivision of ALS Research, Aichi Medical University School of MedicineAmyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10-8); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10−9). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p = 0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417122025Sequential Bilateral Central Retinal Vein Occlusion With Differential Long-Term Outcomes Following Cardiac Surgerye100045ENToshihikoMatsuoOphthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama University HospitalZenichiMasudaCardiovascular Surgery, Okayama University HospitalHirokiSugiyamaCardiovascular Medicine, Okayama University HospitalKazufumiNakamuraCardiovascular Medicine and Center for Advanced Heart Failure, Okayama University HospitalBilateral central retinal vein occlusion (CRVO) is rare and is associated with systemic diseases such as hypertension, diabetes, dyslipidemia, and coagulopathy. In this study, we showed that the sequential development of bilateral CRVO in an elderly patient was related to increased venous pressure in the right heart system. A 71-year-old man developed CRVO in the right eye, and one year later, he developed CRVO in the left eye. He had undergone pacemaker implantation for sick sinus syndrome 10 years earlier and had started hemodialysis three months prior for chronic renal failure, probably caused by hypertensive nephrosclerosis. The right CRVO resulted in neovascular glaucoma and loss of light perception despite intensive treatment with panretinal laser photocoagulation, intravitreal bevacizumab injection, and additional laser therapy. In contrast, the left CRVO remained at an impending stage, was treated only with panretinal laser photocoagulation, and had a favorable outcome for 11 years until his death. In retrospect, half a year after the onset of left CRVO, the patient underwent open-heart surgery to repair aortic, mitral, and tricuspid valve regurgitation through aortic valve replacement, mitral valve annuloplasty, and tricuspid valve annuloplasty, respectively. Based on the temporal sequence of events, elevated venous pressure due to right heart dysfunction may have contributed to the poor outcome of the right CRVO, whereas improvement of venous stasis after cardiac surgery may have led to the better long-term outcome of the left CRVO. Venous stasis in the right heart system should therefore be considered an underlying factor in the development of bilateral CRVO.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7962025Association of Weekend Admission and In-Hospital Mortality in Adult Patients with Acute Myeloid Leukemia in Japan431436ENTakahiroInoueHealthcare Management Research Center, Chiba University HospitalHiroyoKuwabaraHealthcare Management Research Center, Chiba University HospitalKohYamamotoDepartment of Hematology, Yokohama City Minato Red Cross HospitalOriginal Article10.18926/AMO/69845The effect of weekend admission on patient mortality has been investigated in several therapeutic areas, including acute myeloid leukemia (AML), but the investigations’ results are controversial. We evaluated the relationship between in-hospital mortality and weekend admission in adult patients with AML in Japan by conducting a retrospective observational study using administrative data from 144 acute care hospitals from which patients were discharged between April 2014 and March 2019. The primary endpoint was in-hospital mortality, compared between weekend and weekday admissions. Among the 1,340 eligible patients, 11% (150) were admitted during a weekend. The in-hospital mortality rates of the patients admitted during weekends and those admitted on a weekday were 28% (42/150) and 17% (204/1190), respectively. After an adjustment for covariates, weekend admission was associated with a significantly higher risk of in-hospital mortality than weekday admission (HR 1.70, 95%CI: 1.20-2.40; p=0.003). However, such an association was not observed in patients treated in a bio-clean room (HR 1.26, 95%CI: 0.65-2.42). Our results demonstrate that for patients with AML, weekend admission was independently associated with a higher risk of death during hospitalization. An appropriate system is necessary for these patients.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96253082025Phase-Ib dose-finding and pharmacokinetic trial of metformin combined with nivolumab for refractory/recurrent solid tumors15371544ENToshioKuboDepartment of Allergy and Respiratory Medicine, Okayama University HospitalHironariKatoDepartment of Gastroenterology, Okayama University HospitalShigeruHoriguchiDepartment of Gastroenterology, Okayama University HospitalToshiyukiKozukiDepartment of Thoracic Oncology and Medicine, NHO Shikoku Cancer CenterAkinoriAsagiDepartment of Gastrointestinal Medical Oncology, NHO Shikoku Cancer CenterMichihiroYoshidaCenter for Innovative Clinical Medicine, Okayama University HospitalHeiichiroUdonoDepartment of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKatsuyukiHottaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalBackground Our previous findings showed that the addition of metformin to nivolumab resulted in remarkable tumor regression and increased the number of tumor-infiltrating T cells in mouse models. Therefore, we conducted a phase Ib study using combination therapy with nivolumab and metformin in patients with refractory/recurrent solid tumors.<br>
Methods This study consisted of two parts: 1, evaluating the maximum tolerated dose (MTD), safety, pharmacokinetics in solid tumors, and 2, principally investigating the safety at the recommended dose limited to thoracic and pancreatic cancers. Metformin and nivolumab were administered orally at doses of 750–2,250 mg/day and biweekly at a fixed intravenous dose of 3 mg/kg, respectively. Dose-limiting toxicity was evaluated within the first 4 weeks. Both metformin and nivolumab were continued until disease progression or discontinued because of toxicity.<br>
Results In total, 17 and 24 patients were enrolled in parts 1 and 2, respectively. One patient experienced increased pancreatic enzyme levels (grade 4) and lactic acidosis (grade 3). No Grade 5 adverse events were observed. MTD was not reached up to 2,250 mg/day of metformin, 2,250 mg/day was selected for part 2. An objective response was observed in 4 of 41 patients. One-year progression-free and overall survival rates were 9.8% and 56.8%, respectively. Two patients remained alive without disease progression for more than three years.<br>
Conclusions Nivolumab and metformin combination therapy was well-tolerated and showed preliminary signals of efficacy in a subset of patients. Further verification of the underlying mechanism in cases where treatment is effective is required.<br>
Trial registration numbers UMIN registration number 000028405 https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031915.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2399-3642812025Single-cell and spatial transcriptomic characterization of pulmonary pleomorphic carcinoma1773ENAtsushiMatsuokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoShienDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShutaTomidaMasayoshiOhkiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaHisamatsuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaFujiwaraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiIshimuraDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyunosukeFujiiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoakiHigashiharaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaohiroHayashiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOkadaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoYoshichikaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumiakiMukoharaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaoYoshikawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumaFukumotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuakiTomiokaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeOtaniDepartment of Pathology, Beth Israel Deaconess Medical CenterAtsushiTanakaDepartment of Pathology, Beth Israel Deaconess Medical CenterHirofumiInoueCenter for Comprehensive Genomic Medicine, Okayama University HospitalYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidetakaYamamotoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPulmonary pleomorphic carcinoma (PPC) is a rare subtype of lung cancer that comprises both epithelial and sarcomatoid components. The molecular basis of PPC, including the cellular dynamics of its components, remains largely unknown. To elucidate potential therapeutic targets for PPC, we perform a multi-omics analysis incorporating digital spatial profiling and single-cell RNA sequencing (scRNA-seq). PPC exhibits diverse driver gene alterations, including MET exon 14 skipping mutation (METex14) and ALK fusion. In spatial transcriptomics, MET gene and protein are overexpressed exclusively within the epithelial component and not in the sarcomatoid component, even in patients harboring METex14. Epithelial-mesenchymal transition (EMT)-related transcriptional changes, along with extracellular matrix (ECM) remodeling between the epithelial and sarcomatoid components, are observed. scRNA-seq identifies cell populations within the epithelial component that contribute to the malignant transformation and differentiation of the sarcomatoid component. They are characterized by an intermediate EMT state with ECM remodeling signature, suggesting their potential as novel therapeutic targets for PPC.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2041-17231612025Efficient and stable n-type sulfide overall water splitting with separated hydrogen production8786ENHaolinLuoResearch Center for Combustion and Environment Technology, Shanghai Jiao Tong UniversityZhixiLiuResearch Center for Combustion and Environment Technology, Shanghai Jiao Tong UniversityHaifengLvState Key Laboratory of Precision and Intelligent Chemistry, School of Chemistry and Material Sciences, and Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), University of Science and Technology of ChinaJunie Jhon M.VequizoInstitute of Aqua Regeneration, Shinshu UniversityMengtingZhengCollege of Chemical and Biological Engineering, Zhejiang UniversityFengHanResearch Center for Combustion and Environment Technology, Shanghai Jiao Tong UniversityZhenYeResearch Center for Combustion and Environment Technology, Shanghai Jiao Tong UniversityAkiraYamakataFaculty of Natural Science and Technology, Okayama UniversityWenfengShangguanResearch Center for Combustion and Environment Technology, Shanghai Jiao Tong UniversityAdam F.LeeCentre for Catalysis and Clean Energy, School of Environment and Science, Griffith UniversityXiaojunWuState Key Laboratory of Precision and Intelligent Chemistry, School of Chemistry and Material Sciences, and Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), University of Science and Technology of ChinaDomenKazunariInstitute of Aqua Regeneration, Shinshu UniversityJunLuCollege of Chemical and Biological Engineering, Zhejiang UniversityZhiJiangResearch Center for Combustion and Environment Technology, Shanghai Jiao Tong UniversityN-type sulfide semiconductors are promising photocatalysts due to their broad visible-light absorption, facile synthesis and chemical diversity. However, photocorrosion and limited electron transport in one-step excitation and solid-state Z-scheme systems hinder efficient overall water splitting. Liquid-phase Z-schemes offer a viable alternative, but sluggish mediator kinetics and interfacial side reactions impede their construction. Here we report a stable Z-scheme system integrating n-type CdS and BiVO₄ with a [Fe(CN)₆]³⁻/[Fe(CN)₆]⁴⁻ mediator, achieving 10.2% apparent quantum yield at 450 nm with stoichiometric H₂/O₂ evolution. High activity reflects synergies between Pt@CrOx and Co3O4 cocatalysts on CdS, and cobalt-directed facet asymmetry in BiVO₄, resulting in matched kinetics for hydrogen and oxygen evolution in a reversible mediator solution. Stability is dramatically improved through coating CdS and BiVO4 with different oxides to inhibit Fe4[Fe(CN)6]3 precipitation and deactivation by a hitherto unrecognized mechanism. Separate hydrogen and oxygen production is also demonstrated in a two-compartment reactor under visible light and ambient conditions. This work unlocks the long-sought potential of n-type sulfides for efficient, durable and safe solar-driven hydrogen production.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1479-58762312025Tumor marker–guided precision BNCT for CA19-9–positive cancers: a new paradigm in molecularly targeted chemoradiation therapy1387ENNoriyukiKanehiraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyukiTajimaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTatsunoriOsoneDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyoshiGotohDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesTakuyaFujimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinoriSakuraiInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityNatsukoKondoInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityNarikazuNagahisaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoruKameiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTaigaFujitaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAkiraMoriharaGraduate School of Environmental, Life Science, Okayama UniversityYutakaTakaguchiFaculty of Sustainable Design, Department of Material Design and Engineering, University of ToyamaMizukiKitamatsuDepartment of Applied Chemistry, Kindai UniversityTakeshiTakaradaDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMinoruSuzukiInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiMichiueNeutron Therapy Research Center, Okayama UniversityBackground: Boron neutron capture therapy (BNCT) is a molecularly targeted chemoradiation modality that relies on boron delivery agents such as p-borophenylalanine (BPA), which require LAT1 (L-type amino acid transporter 1) for tumor uptake. However, the limited efficacy of BPA in LAT1-low tumors restricts its therapeutic scope. To address this limitation, we developed a tumor marker–guided BNCT strategy targeting cancers overexpressing the clinically validated glycan biomarker CA19-9.<br>
Methods: We conducted transcriptomic analyses using The Cancer Genome Atlas (TCGA) datasets to identify LAT1-low cancers with high CA19-9 expression. These analyses revealed elevated expression of fucosyltransferase 3 (FUT3), which underlies CA19-9 biosynthesis, in pancreatic, biliary, and ovarian malignancies. Based on this, we synthesized a novel boron compound, fucose-BSH, designed to selectively accumulate in CA19-9–positive tumors. We evaluated its physicochemical properties, pharmacokinetics, biodistribution, and antitumor efficacy in cell lines and xenograft models, comparing its performance to that of BPA.<br>
Results: Fucose-BSH demonstrated significantly greater boron uptake in CA19-9–positive cell lines (AsPC-1, Panc 04.03, HuCCT-1, HSKTC, OVISE) compared to CA19-9–negative PANC-1. In HuCCT-1 xenografts, boron accumulation reached 36.2 ppm with a tumor/normal tissue ratio of 2.1, outperforming BPA. Upon neutron irradiation, fucose-BSH–mediated BNCT achieved > 80% tumor growth inhibition. Notably, fucose-BSH retained therapeutic efficacy in LAT1-deficient models where BPA was ineffective, confirming LAT1-independent targeting.<br>
Conclusions: This study establishes a novel precision BNCT approach by leveraging CA19-9 as a tumor-selective glycan marker for boron delivery. Fucose-BSH offers a promising platform for expanding BNCT to previously inaccessible LAT1-low malignancies, including pancreatic, biliary, and ovarian cancers. These findings provide a clinically actionable strategy for tumor marker–driven chemoradiation and lay the foundation for translational application in BNCT. This strategy has the potential to support companion diagnostic development and precision stratification in ongoing and future BNCT clinical trials.<br>
Translational Relevance: Malignancies with elevated CA19-9 expression, such as pancreatic, biliary, and ovarian cancers, are associated with poor prognosis and limited response to current therapies. This study presents a tumor marker–guided strategy for boron neutron capture therapy (BNCT) by leveraging CA19-9 glycan biology to enable selective tumor targeting via fucose-BSH, a novel boron compound. Through transcriptomic data mining and preclinical validation, fucose-BSH demonstrated LAT1-independent boron delivery, potent BNCT-mediated cytotoxicity, and tumor-specific accumulation in CA19-9–positive models. These findings support a precision chemoradiation approach that addresses a critical gap in BNCT applicability, offering a clinically actionable pathway for patient stratification and therapeutic development in CA19-9–expressing cancers.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0944-117460122025Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B)15841595ENSatoshiKobayashiDepartment of Gastroenterology, Kanagawa Cancer CenterKoheiNakachiDepartment of Medical Oncology, Tochigi Cancer CenterKoujiYamamotoDepartment of Biostatistics, Yokohama City University School of MedicineMakotoUenoDepartment of Gastroenterology, Kanagawa Cancer CenterYutaMarukiKenjiIkezawaDepartment of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer InstituteTakeshiTerashimaDepartment of Gastroenterology, Kanazawa University HospitalSatoshiShimizuDepartment of Gastroenterology, Kanazawa University HospitalKotoeOshimaDivision of Gastrointestinal Oncology, Shizuoka Cancer CenterKunihiroTsujiDepartment of Gastroenterology, Ishikawa Prefectural Central HospitalYoshiharuMasakiDepartment of Gastroenterology and Hepatology, Sapporo Medical University School of MedicineHidetakaTsumuraDepartment of Gastroenterological Oncology, Hyogo Cancer CenterTaroShibukiDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital EastMasatoOzakaHepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer ResearchNaohiroOkanoDepartment of Medical Oncology, Kyorin University Faculty of MedicineYukiyasuOkamuraDivision of Digestive Surgery, Department of Surgery, Nihon University School of MedicineKumikoUmemotoDepartment of Clinical Oncology, St. Marianna University School of MedicineTatsunoriSatohDepartment of Gastroenterology, Shizuoka General HospitalYasushiKojimaDepartment of Gastroenterology, National Center for Global Health and MedicineKazuhikoShiojiDepartment of Gastroenterology, Niigata Cancer Center HospitalHirokoNebikiDepartment of Gastroenterology, Osaka City General HospitalToshifumiDoiDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineAtsushiNaganumaDepartment of Gastroenterology, National Hospital Organization Takasaki General Medical CenterShigekiKataokaDepartment of Clinical Oncology, Graduate School of Medicine Faculty of Medicine, Kyoto UniversityEmiriKitaDepartment of Gastroenterology, Chiba Cancer CenterHiroyukiAsamaDepartment of Gastroenterology, Fukushima Medical UniversityKaoruTsuchiyaDepartment of Gastroenterology and Hepatology, Musashino Red Cross HospitalMichiakiUnnoDepartment of Surgery, Tohoku University Graduate School of MedicineReikoAshidaSecond Department of Internal Medicine, Wakayama Medical UniversityKazuyukiMatsumotoDepartment of Gastroenterology, Okayama University Graduate School of MedicineIzumiOhnoDepartment of Gastroenterology, Chiba University Graduate School of MedicineTakaoItoiDepartment of Gastroenterology, Tokyo Medical UniversityYujiNegoroDepartment of Oncologial Medicine, Kochi Health Sciences CenterYasunariSakamotoDepartment of Gastroenterology and Hepatology, International University of Health and Welfare Atami HospitalShihoArimaDigestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental SciencesAkinoriAsagiDepartment of Gastroenterology, National Hospital Organization Shikoku Cancer CenterHiroyukiOkuyamaDepartment of Medical Oncology, Kagawa University HospitalYoshitoKomatsuDepartment of Cancer Chemotherapy, Hokkaido University Hospital Cancer CenterNoritoshiKobayashiDepartment of Oncology, School of Medicine Graduate School of Medicine, Yokohama City UniversityHiroakiNaganoDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineJunjiFuruseDepartment of Gastroenterology, Kanagawa Cancer CenterBackground: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.<br>
Methods: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.<br>
Results: This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55–1.17) and 0.55 for PFS (95% CI 0.38–0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42–1.29) and 0.79 for PFS (95% CI 0.42–1.49).<br>
Conclusions: GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0944-11742025Mortality and cancer risk in patients with chronic pancreatitis in japan: insights into the importance of surveillance for pancreatic cancerENRyotaroMatsumotoDivision of Gastroenterology, Tohoku University Graduate School of MedicineKazuhiroKikutaDivision of Gastroenterology, Tohoku University Graduate School of MedicineTetsuyaTakikawaDivision of Gastroenterology, Tohoku University Graduate School of MedicineYousukeNakaiDepartment of Gastroenterology, Graduate School of Medicine, The University of TokyoMamoruTakenakaDepartment of Gastroenterology and Hepatology, Kindai University Faculty of MedicineKentaroOkiDepartment of Gastroenterology and Hepatology, Kurashiki Central HospitalEizaburoOhnoDepartment of Gastroenterology and Hepatology, Fujita Health University School of MedicineKenItoDivision of Gastroenterology and Hepatology, Toho University Omori Medical CenterNaoFujimoriDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu UniversityAkioKatanumaCenter for Gastroenterology, Teine-Keijinkai HospitalAtsuhiroMasudaDivision of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of MedicineYasukiHoriDepartment of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical SciencesTsukasaIkeuraDepartment of Gastroenterology and Hepatology, Kansai Medical UniversityReiSuzukiDepartment of Gastroenterology, Fukushima Medical University School of MedicineSatoshiYamamotoDepartment of Gastroenterology, Fujita Health University Bantane HospitalYoshioSogameDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineHirokiKawashimaDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of MedicineTetsuhideItoNeuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and WelfareKosukeOkuwakiDepartment of Gastroenterology, Kitasato University School of MedicineTakaoItoiDepartment of Gastroenterology and Hepatology, Tokyo Medical UniversityYukikoTakayamaDepartment of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical UniversityAkiraNakamuraDepartment of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of MedicineShujiTeraiDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata UniversityKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalMasakiKuwataniDepartment of Gastroenterology and Hepatology, Hokkaido University HospitalMasashiKishiwadaDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of MedicineMinoruShigekawaDepartment of Gastroenterology and Hepatology, The University of Osaka Graduate School of MedicineTomoakiMatsumoriDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of MedicineOsamuInatomiDepartment of Medicine, Shiga University of Medical ScienceWakuHattaDivision of Gastroenterology, Tohoku University Graduate School of MedicineAtsushiIrisawaDepartment of Gastroenterology, Dokkyo Medical University School of MedicineMichiakiUnnoDepartment of Surgery, Tohoku University Graduate School of MedicineYoshifumiTakeyamaDepartment of Surgery, Kindai University Faculty of MedicineAtsushiMasamuneDivision of Gastroenterology, Tohoku University Graduate School of MedicineJapan Pancreatitis Study Group for Chronic PancreatitisBackground/Objective: Since the 2010s, Japan’s national health insurance system has covered key management for chronic pancreatitis (CP), including pancreatic enzyme replacement therapy. These therapies are expected to improve long-term prognosis; however, recent data are lacking. This study aimed to clarify the updated cancer risk and mortality among patients with CP in Japan.<br>
Methods: We conducted a multicenter, retrospective cohort study on 1,110 patients with CP treated at 28 institutions in 2011. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated for comorbidities. Factors associated with the development of malignancy and overall survival were analyzed.<br>
Results: Patients with CP had an elevated SIR of 1.62 (95% confidence interval [CI], 1.43–1.83) for malignancy, with the highest risk observed for pancreatic cancer (SIR = 6.44 [95% CI, 4.64–8.90]). During follow-up, 143 patients (12.9%) died, most frequently from malignancy (47.5%). The SMR was elevated in all patients with CP (SMR = 1.20 [95% CI, 1.01–1.42]) and in those with alcohol-related CP (SMR = 1.49 [95% CI, 1.23–1.81]) but not in those with alcohol-unrelated CP. Pancreatic cancer was identified as the strongest factor associated with overall survival (hazard ratio, 48.92 in multivariate analysis). Overall survival of the patients with pancreatic cancer was significantly longer in those who underwent regular examinations for CP at least every three months (P = 0.011).<br>
Conclusions: Patients with alcohol-related CP have higher mortality than the general population in Japan. Pancreatic cancer remains a crucial prognostic factor in patients with CP. Regular surveillance for pancreatic cancer is important to improve their prognosis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0941-435533122025Factors associated with period of sick leave after gynecologic cancer treatment: a prospective cohort study1087ENYoshinoriTaniDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKeiichiroNakamuraDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHanakoSugiharaDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShinsukeShirakawaDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHirofumiMatsuokaDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNaoyukiIdaDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineJunkoHaragaDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineChikakoOgawaDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineErikoEtoDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShojiNagaoDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHisashiMasuyamaDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicinePurpose Gynecologic cancer is one of the most common malignancies in working-age women. This study aimed to investigate factors associated with period of sick leave after gynecologic cancer treatment in Japan.<br>
Methods A prospective cohort study on period of sick leave was conducted among 207 cancer survivors who returned to work at the same workplace. Questionnaires were randomly distributed to patients aged under 65 years and more than one-year post-treatment. Clinical information was extracted from medical records, and the factors influencing the period of sick leave were analyzed using the Mann–Whitney U test and logistic regression analysis.<br>
Results Surgery plus more than six courses of chemotherapy (number (n) = 41, 166.02 ± 146.84 days) led to a significantly longer period of sick leave than surgery without lymph node dissection (n = 64, 31.15 ± 30.47 days), surgery with lymph node dissection (n = 41, 55.56 ± 85.90 days), surgery plus less than six courses of chemotherapy (n = 21, 72.42 ± 56.07 days), and radiotherapy alone (n = 21, 58.85 ± 84.24 days) (OR: 2.63, 2.95, 2.67, and 2.08; 95% CI: 7.71–54.59, 18.17–92.94, 18.22–126.63, and 2.38–115.33; p = 0.009, p = 0.004, p = 0.009, and p = 0.041). gynecologic cancer survivors who experienced adverse effects after treatment had a significantly longer period of sick leave (OR: 8.50; CI: 52.98–84.98; p < 0.001). In univariate and multivariate analyses, patients who received surgery plus more than six courses of chemotherapy were most involved in long period of sick leave than other factors (OR: 11.20, and 16.997; CI: 4.86–25.08, and 5.51–52.35; p < 0.001, and p < 0.001).<br>
Conclusion Patients with gynecologic cancer requiring long-term treatment required the most time to return to work.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Association between gestational age and child health and neurodevelopment in twins from a nationwide longitudinal survey in Japan40608ENKeiTamaiDepartment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaomiMatsumotoDepartment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAkihitoTakeuchiDivision of Neonatology, NHO Okayama Medical CenterMakotoNakamuraDivision of Neonatology, NHO Okayama Medical CenterMisaoKageyamaDivision of Neonatology, NHO Okayama Medical CenterTakashiYorifujiDepartment of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDespite previous research, evidence on the relationship between gestational age and long-term health and neurodevelopmental outcomes among twins remains limited. Using data from the Longitudinal Survey of Babies in the 21st Century, we analyzed 549 twins born in Japan in 2010. The twins were grouped by gestational age: <32 weeks (very preterm), 32–36 weeks (moderately and late preterm), and 37–38 weeks (early term). The health status was evaluated by hospitalization between 0.5 and 5.5 years, and behavioral development was assessed using questionnaires at 2.5 and 5.5 years. Binomial log-linear regression with generalized estimating equations accounted for within-pair correlations and adjusted for child and parental variables. Moderately and late preterm children showed a higher risk of all-cause hospitalization during infancy than early-term children (adjusted risk ratio, 1.7; 95% CI, 1.0–2.6). Very preterm children showed a higher point estimate of the risk ratio, but a wide CI (risk ratio, 2.3; 95% CI, 0.8–6.8). Behavioral delays were more common in preterm groups at 2.5 years but not at 5.5 years. Preterm twins have a higher risk of hospitalization during infancy and developmental delay at 2.5 years than early-term twins. These risks show an increasing trend as gestational age decreases.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417102025Association of Use of GRADE, Protocol Registration, and Journal Impact Factor With Reporting and Methodological Quality of Systematic Reviews Published in Rehabilitation Journals: A Meta-Epidemiological Studye95695ENTakahiroTsugeDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNorioYamamotoSystematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG)YosukeTomitaPhysical Therapy, Faculty of Health Care, Takasaki University of Health and WelfareAkikazuHagiyamaDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDaijoShiratsuchiPhysical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima UniversityMasatsuguOkamuraSystematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG)TakaoKanekoRehabilitation, Yamagata Prefectural Central HospitalKosukeSuzukiRehabilitation, Yamagata Saisei HospitalYukiNakashimaSystematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG)ShunsukeTaitoSystematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG)TakashiYorifujiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThis study aimed to identify factors associated with the reporting and methodological quality of systematic reviews (SRs) published in rehabilitation journals. We conducted a meta-epidemiological study as a secondary analysis of a previous study. The study protocol was registered in the Open Science Framework. We analyzed 219 SRs from rehabilitation journals published since 2020. We assessed reporting quality using the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 and methodological quality using A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2. Multiple linear regression and Spearman's correlation were used to identify factors associated with quality, including Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and the Journal Impact Factor (JIF). Multivariate analysis revealed PRISMA 2020 adherence was significantly associated with use of GRADE (β = 4.33; 95% confidence interval (CI): 3.24-5.42), protocol registration (β = 3.40; 95% CI: 2.32-4.47), and the JIF (2023) (β = 0.69; 95% CI: 0.42-0.95). AMSTAR 2 adherence was also significantly associated with use of GRADE (β = 2.52; 95% CI: 1.88-3.17), protocol registration (β = 2.07; 95% CI: 1.44-2.70), and the JIF (2023) (β = 0.29; 95% CI: 0.14-0.45). Weak positive correlations were observed between the JIF (2023) and both PRISMA 2020 and AMSTAR 2 adherence (ρ = 0.27 and ρ = 0.22, respectively; both P < 0.01). It should be noted that these findings reflect associations and do not imply causality. To enhance the quality of SRs in rehabilitation, researchers should prioritize adherence to PRISMA 2020, particularly the use of GRADE and protocol registration, which this study identified as key associated factors.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Long intervals between repetitive concussions reduce risk of cognitive impairment and limit microglial activation, astrogliosis, and tauopathy in adolescent rats40522ENYuichiHirataDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalKyoheiKinDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalTakayukiNagaseDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalTatsuyaSasakiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalSusumuSasadaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalChiakiSugaharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalTakahiroHirayamaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University HospitalKojiKawaiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalShunTanimotoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalHayatoMiyakeDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalTomoyaSaijoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University HospitalKaoriMasaiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoYasuharaYasuhara ClinicShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HospitalAlthough previous studies have demonstrated the effects of concussions do not accumulate as the time interval between injuries increases, little is known about the relationship between this interval and the effects of repetitive concussions. The objective of this study is to explore the relationship between the time interval and changes in behavior and histology following repetitive concussions. Male adolescent rats received concussions by weight drop and were randomly assigned to one of five experimental groups, receiving concussions three times either daily, every other day, once per week, once every 2 weeks, or receiving sham procedures. Only rats that received daily concussions exhibited cognitive impairment, while the other groups did not. No groups showed motor or anxiety-like impairments. Histological analysis revealed accumulation of microglia, as well as astrogliosis, in the prefrontal cortex, corpus callosum, dentate gyrus, and cornu Ammonis 1 region of the hippocampus in rats subjected to daily concussions. Accumulation of phosphorylated tau was also observed in the prefrontal cortex and cornu Ammonis 1. Longer intervals between concussions may reduce the risk of cognitive impairment and limit microglial activation, astrogliosis, and phosphorylated tau accumulation. These findings may help guide decisions on the appropriate timing for return to play in humans.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1478-63622712025Does perioperative discontinuation of anti-rheumatic drugs increase postoperative complications in orthopedic surgery for rheumatoid arthritis?219ENHiromuItoDepartment of Orthopaedic Surgery, Kurashiki Central HospitalHajimeIshikawaDepartment of Rheumatology, Niigata Rheumatic CenterShigeyoshiTsujiDepartment of Orthopaedic Surgery, Osaka Minami Medical CenterMasanoriNakayamaDepartment of Orthopaedic Surgery, International University of Health and WelfareKeiichiroNishidaLocomotive Pain Center, Okayama University HospitalTakeshiMochizukiDepartment of Orthopaedic Surgery, Kamagaya General HospitalKosukeEbinaDepartment of Orthopaedic Surgery, Osaka University Faculty of Medicine Graduate School of MedicineToshihisaKojimaDepartment of Orthopaedic Surgery, Nagoya University HospitalTakumiMatsumotoDepartment of Orthopaedic Surgery, University of TokyoAyakoKubotaDepartment of Orthopaedic Surgery, Toho University Omori Medical CenterArataNakajimaDepartment of Orthopaedic Surgery and Rehabilitation, Toho University Sakura Medical CenterAtsushiKanekoDepartment of Orthopaedic Surgery, Nagoya Medical CenterIsaoMatsushitaDepartment of Rehabilitation Medicine, Kanazawa Medical UniversityRyotaHaraThe Center for Rheumatic Diseases, Nara Medical UniversityKojiSakurabaDepartment of Orthopaedic Surgery, Kyushu Medical CenterYukioAkasakiDepartment of Orthopaedic Surgery, Kyushu UniversityTsukasaMatsubaraDepartment of Orthopaedic Surgery, Matsubara Mayflower HospitalYuichiMochidaDepartment of Orthopaedic Surgery, Yokohama City University Medical CenterKatsuakiKanbeDepartment of Orthopaedic Surgery, Nippori Orthopaedics and Rheumatic ClinicNatsukoNakagawaDepartment of Orthopaedic Surgery, Kakogawa Medical CenterKoichiMurataDepartment of Orthopaedic Surgery, Kyoto University Graduate School of MedicineShigekiMomoharaEndowed Course for Advanced Therapy for Musculoskeletal Disorders, Keio University School of MedicineObjective This study aimed to investigate whether discontinuation of biological or targeted synthetic antirheumatic disease-modifying drugs (bDMARDs or tsDMARDs) influences the incidence of postoperative complications in patients with rheumatoid arthritis (RA) undergoing orthopedic surgery.<br>
Methods A retrospective multicenter cohort study including patients receiving bDMARDs or tsDMARDs who underwent orthopedic surgery was conducted. Data collected encompassed the duration of drug discontinuation and postoperative adverse events, such as delayed wound healing, surgical site infection (SSI), disease flare-ups, and mortality. The association between drug discontinuation and these outcomes was analyzed. Multivariate analyses were conducted to identify potential risk factors for these events.<br>
Results A total of 2,060 cases were initially enrolled. After applying inclusion and exclusion criteria, data from 1,953 patients were analyzed. No significant differences were observed between the groups regarding delayed wound healing, SSI, or mortality. However, the incidence of disease flare-ups was substantially higher in the drug discontinuation group and in the interleukin (IL)-6 inhibitor group. Multivariate analysis identified that tumor necrosis factor α and IL-6 inhibitor use was associated with a higher risk of delayed wound healing relative to T-cell function modifiers.<br>
Conclusion In orthopedic surgery for patients with RA, maintaining the standard or the half of administration interval of bDMARD appears safe in the preoperative period. However, the drug discontinuation may increase the risk of postoperative flare-ups, particularly with IL-6 inhibitors. In addition, T-cell function modifiers may be associated with a lower risk of delayed wound healing, suggesting their safety profile in this context.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2050-65112612025PEGylation of liposome-encapsulated midazolam does not improve the bioavailability of midazolam when administered orally166ENYukikoNishiokaDepartment of Dental Anesthesiology, Okayama University HospitalYanyinLuDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiHiguchiDepartment of Dental Anesthesiology, Okayama University HospitalSakiMiyakeDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMakiFujimotoDepartment of Dental Anesthesiology, Okayama University HospitalMidoriHamaoka-InoueDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTanimuraDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitomiUjitaDepartment of Dental Anesthesiology, Okayama University HospitalShigeruMaedaDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaMiyawakiDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground Liposomes are closed vesicles made of the same phospholipid bilayer as biological membranes and are capable of containing drugs, and so they have been investigated as useful drug carriers for drug delivery. We previously developed liposome-encapsulated midazolam (LE-midazolam) for oral administration, but midazolam is metabolized in the liver, and for clinical use the encapsulation of the liposomes needed to be improved to increase the bioavailability of midazolam. The surfaces of pharmaceutical liposomes are generally coated with polyethylene glycol (PEGylation) because it prevents their capture by phagocytes and helps them to avoid the reticuloendothelial system. Therefore, we considered that PEGylation could reduce the metabolism of orally administered encapsulated midazolam in the liver.<br>
Methods Midazolam solution, LE-midazolam solution, and PEGylated liposome-encapsulated midazolam (PEG-LE-midazolam) solution were prepared, and the characteristics of the liposomes in these solutions were evaluated. Furthermore, these solutions were orally administered to rabbits, and the resultant plasma midazolam concentrations were measured. The effects of the PEGylation of LE-midazolam on the plasma concentration and bioavailability of orally administered midazolam were also evaluated.<br>
Results The PEG-LE-midazolam solution contained a higher percentage of larger liposomes than the LE-midazolam solution. The area under the concentration-time curve (AUC) of the LE-midazolam solution was significantly higher than that of the midazolam solution, but there was no difference between the AUC values of the PEG-LE-midazolam and midazolam solutions.<br>
Conclusions These findings suggest that liposome encapsulation may reduce the first-pass effect following oral administration, but PEGylation is not expected to improve the bioavailability of orally administered midazolam.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0944-11746052025Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn’s disease activity in the small bowel573582ENMuneyoriOkitaDepartment of Biostatistics, Nagoya University Graduate School of MedicineKentoTakenakaDepartment of Gastroenterology and Hepatology, Institute of Science TokyoFumihitoHiraiDepartment of Gastroenterology and Medicine, Fukuoka University Faculty of MedicineShinyaAshizukaDepartment of Gastroenterology and Medicine, Fukuoka University Faculty of MedicineHidekiIijimaOsaka International Medical & Science Center, Osaka Keisatsu HospitalShigekiBambaDepartment of Fundamental Nursing, Shiga University of Medical ScienceToshimitsuFujiiDepartment of Gastroenterology and Hepatology, Institute of Science TokyoKenjiWatanabeDepartment of Internal Medicine for Inflammatory Bowel Disease, Toyama UniversityYosukeShimodairaDepartment of Gastroenterology and Neurology, Akita University Graduate School of MedicineHisashiShigaDivision of Gastroenterology, Tohoku University Graduate School of MedicineSakikoHiraokaDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToshihiroInokuchiResearch Center for Intestinal Health Science, Okayama UniversityTakeshiYamamuraDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of MedicineRyoEmotoDepartment of Biostatistics, Nagoya University Graduate School of MedicineShigeyukiMatsuiDepartment of Biostatistics, Nagoya University Graduate School of MedicineBackground Small bowel (SB) lesions in Crohn’s disease (CD) are often asymptomatic despite being highly active. Fecal calprotectin (FC) is the most widely used biomarker of CD activity, but its drawbacks include a large intra-individual sample variability and the burden of collecting stool samples. Meanwhile, serum leucine-rich alpha-2 glycoprotein (LRG) has recently attracted attention as a biomarker that can address the limitations of FC. This study determined the diagnostic accuracy of LRG and its cut-off values for diagnosing CD activity in SB.<br>
Methods This was a retrospective, multi-center study of CD patients undergoing retrograde balloon-assisted endoscopy. For ileal- and ileocolonic-type patients with a colon SES-CD score of 0, we estimated the receiver operating characteristic curve of LRG and determined the cut-off value to achieve a target sensitivity level of 80%.<br>
Results Among 285 patients with SB lesions, LRG had an area under the curve (AUC) of 0.72 (95% CI 0.67–0.78) with a sensitivity of 80.2% and specificity of 47.2% for a cut-off value of 10.5 when diagnosing endoscopic remission (modified SES-CD ≤ 3), while it had an AUC of 0.72 (95% CI 0.65–0.78) with a sensitivity of 81.2% and specificity of 46.2% for a cut-off value of 10.1 when diagnosing complete ulcer healing (modified SES-CD ≤ 1).<br>
Conclusion LRG was effective for diagnosing CD activity in SB, specifically with cut-off values of 10.5 and 10.1 for endoscopic remission and complete ulcer healing, respectively. A future prospective validation study will assess its clinical utility.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72572025Avoiding splenectomy in splenic sclerosing angiomatoid nodular transformation through endoscopic ultrasound-guided tissue acquisition: a 36-month follow-up case reportENTakakiOkuyamaDepartment of Internal Medicine, Tsuyama Chuo HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKosakuMorimotoDepartment of Internal Medicine, Tsuyama Chuo HospitalShogoKimuraDepartment of Internal Medicine, Tsuyama Chuo HospitalTakayoshiMiyakeDepartment of Pathology, Tsuyama Chuo HospitalTakuyaSatomiDepartment of Internal Medicine, Tsuyama Chuo HospitalKensukeTakeiDepartment of Internal Medicine, Tsuyama Chuo HospitalShogoInoueDepartment of Internal Medicine, Tsuyama Chuo HospitalRyutaTakenakaDepartment of Internal Medicine, Tsuyama Chuo HospitalA 48-mm splenic mass was incidentally discovered in a 78-year-old man upon computed tomography. Follow-up imaging at 12 months revealed enlargement to 60 mm, prompting endoscopic ultrasound-guided tissue acquisition with a 22-gauge needle. Histopathological analysis confirmed that it was a sclerosing angiomatoid nodular transformation. The patient was asymptomatic and had no hematologic abnormalities; therefore, splenectomy was not performed. After biopsy, the lesion regressed from 60 mm to 46 mm, possibly owing to hematoma formation or vascular disruption, and remained stable during 36 months of follow-up. Although splenectomy has been performed in most reported cases of sclerosing angiomatoid nodular transformation because of diagnostic uncertainty, a few recent reports have demonstrated that sclerosing angiomatoid nodular transformation can be diagnosed by endoscopic ultrasound-guided tissue acquisition, thereby avoiding splenectomy. This case highlights the diagnostic utility of endoscopic ultrasound-guided tissue acquisition and supports spleen-preserving management for biopsy-proven sclerosing angiomatoid nodular transformation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1433-73982025A rare case of supratentorial ependymosarcoma harboring ZFTA::RELA fusionENYujiMatsumotoDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasukiSurugaDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKaishiSatomiDepartment of Pathology, Faculty of Medicine, Kyorin UniversityYoheiInoueDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasuhikoHattoriDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineJojiIshidaDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKazuhikoKurozumiDepartment of Neurosurgery, Hamamatsu University HospitalSumihitoNobusawaDepartment of Human Pathology, Gunma University School of MedicineJunkoHiratoDepartment of Pathology, Public Tomioka General HospitalTakehiroTanakaDepartment of Pathology, Okayama University HospitalHiroyukiYanaiDepartment of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKanaWashioDepartment of Pediatrics, Okayama University HospitalKoichiIchimuraDepartment of Pathology, Faculty of Medicine, Kyorin UniversityTomotsuguIchikawaDepartment of Neurosurgery, Kagawa Prefectural Central HospitalYoshihiroOtaniDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShotaTanakaDepartment of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineEpendymosarcoma is an exceedingly rare variant of ependymoma characterized by a mixture of ependymomatous and sarcomatous components. We report a case of supratentorial ependymosarcoma harboring a ZFTA::RELA fusion in a 10-year-old girl. Histologically, the tumor comprised an ependymomatous component resembling clear cell ependymoma and a sarcomatous component. ZFTA::RELA fusion was confirmed in both components. Genome-wide methylation profiling classified both components as supratentorial ependymoma, ZFTA fusion–positive by the German Cancer Research Center (DKFZ) CNS tumor classifier v12b8. However, their copy number alteration profiles were distinct. The ependymomatous component exhibited a gain of chromosome 1q and a loss of chromosomes 1p, 9, and 19q, while the sarcomatous component showed a loss of chromosome 14. These findings suggest that both components may have differentiated from a common precursor despite their distinct morphologies. The patient underwent gross total resection followed by adjuvant chemoradiotherapy and remains recurrence-free eight years post-treatment. Further investigation of additional cases is warranted to better understand the pathogenesis of this rare tumor.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417102025Risk Stratification for the Prediction of Skeletal-Related Events in Patients With Bone Metastases From Non-small Cell Lung Cancere95808ENYoshihiroSakamotoDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEijiNakataDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasanoriHamadaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshimiKatayamaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinsukeSugiharaDepartment of Orthopedic Surgery, Shikoku Cancer CenterToshifumiOzakiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSkeletal-related events (SREs) frequently occur in patients with bone metastases from non-small cell lung cancer (NSCLC). This study aimed to identify risk factors for SREs in patients with NSCLC. Based on these factors, we also aimed to stratify patients into subgroups to facilitate the assessment of SRE risk. This retrospective analysis used medical records of 139 patients with NSCLC bone metastases who received treatment at our institution between 2011 and 2014. The incidence of SREs was assessed, and SRE-free survival was analyzed using the Kaplan-Meier method. Clinical information collected at registration was assessed to identify factors associated with the onset of SREs within six months. Univariate analysis was performed using Fisher’s exact test, and multivariate analysis was performed using Cox regression. Of the 139 patients, 36 (26%) developed SREs after registration. The SRE-free survival rates were 80% and 64% at 6 and 12 months, respectively. The univariate and multivariate analyses revealed that the absence of epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangement (hazard ratio (HR): 4.51, 95% confidence interval (CI): 1.32-15.7, p = 0.017) and a lactate dehydrogenase (LDH) level ≥400 U/L (HR: 8.08, 95% CI: 1.78-36.6, p = 0.0067) were risk factors for SRE presentation within six months. Patients were classified into the following three subgroups: with EGFR mutation or ALK rearrangement and LDH level <400 U/L; without EGFR mutation or ALK rearrangement and LDH level <400 U/L; with/without EGFR mutation or ALK rearrangement and LDH level ≥400 U/L. The corresponding six-month SRE-free survival rates were 92%, 69%, and 34%, respectively, showing significant differences (p < 0.001). Close monitoring is recommended for patients with LDH levels ≥400 U/L in daily clinical practice, particularly with the help of the proficiency of orthopedic and radiological experts, to prevent complications such as pathological fractures and paraplegia.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841782025Conversion to Hip Arthroplasty After Internal Fixation Failure in an Intertrochanteric Femoral Fracture: A Case Reporte90112ENShiroFukuokaDepartment of Orthopedics, Kagawa Prefectural Central HospitalTomooInoueDepartment of Orthopedics, Kagawa Prefectural Central HospitalMotokiTakahashiDepartment of Orthopedics, Kagawa Prefectural Central HospitalKeisukeKawasakiDepartment of Orthopedic Surgery, Kagawa Prefectural Central HospitalToshifumiOzakiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceIntertrochanteric femoral fractures are mainly managed by internal fixation. However, failures such as over-telescoping, cut-out, nonunion, or implant failure can occur, especially in osteoporotic elderly patients. We report the case of a patient in whom we performed artificial hip replacement surgery after fixation failure following internal fixation of an intertrochanteric femoral fracture. We report the case of an 85-year-old woman who sustained a left intertrochanteric femoral fracture treated with a dynamic hip screw (DHS). One week postoperatively, radiographs revealed over-telescoping of the lag screw. The patient did not complain of pain, but she underwent conversion to cemented bipolar hemiarthroplasty under general anesthesia. One possible cause of over-telescoping of the lag screw after surgery was that the longitudinal fracture line in the calcar of the proximal bone fragment, as seen in the initial CT image, may have extended horizontally at the neck level. During surgery, a fracture at the same site caused the anterior medial fragment to fail, resulting in a coronal shear fracture and fixation failure. When a longitudinal fracture line is observed in the calcar of the proximal fragment, it is necessary to keep in mind that it may extend horizontally at the neck level.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841762025Clinical Outcomes and Biomechanical Evaluation of the Cement-Catching Screw Technique for Osteoporotic Vertebral Fracturese85955ENHisakazuShitozawaDepartment of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruoMisawaDepartment of Orthopaedic Surgery, Ryusou Orthopaedic HospitalYoshiakiOdaDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyojiJokoDepartment of Orthopaedic Surgery, Japanese Red Cross Okayama HospitalMasayaTakahashiDepartment of Orthopaedic Surgery, Japanese Red Cross Okayama HospitalKojiUotaniDepartment of Orthopaedic Surgery, Okayama University HospitalYasuyukiShiozakiDepartment of Orthopaedic surgery, Mitoyo General HospitalTomokoTetsunagaDepartment of Orthopaedic Surgery, Okayama University HospitalKensukeShinoharaDepartment of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyoNakamichiDepartment of Orthopaedic Surgery, Okayama University HospitalMasatakaUedaDepartment of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoTakatoriDepartment of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazutakaYamashitaDepartment of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityObjectives: We developed a cement-catching screw (CCS) technique for pedicle screw insertion into hardened cement, connecting anterior and posterior vertebral elements during balloon kyphoplasty (BKP) for osteoporotic vertebral fractures (OVFs). This study reports the CCS technique, clinical outcomes, and biomechanical properties.<br>
Methods: This retrospective study included 59 patients (20 men, 39 women; mean age, 77.4 ± 8.7 years) who underwent BKP with one-above-one-below posterior fixation for OVFs between 2020 and 2023. Patients were divided into CCS (−) (without intermediate screws, n = 28) and CCS (+) (with intermediate CCSs, n = 31) groups. Clinical and radiographic outcomes, including activities of daily living, vertebral wedge angle (VWA), surgical level Cobb angle (CA), anterior vertebral body height (AVBH), screw loosening, pullout, and adjacent vertebral fractures, were evaluated preoperatively, postoperatively, and at the final follow-up (≥6 months). Biomechanical pullout strength was assessed at different insertion depths (5, 10, and 15 mm) using polymethylmethacrylate cement.<br>
Results: No significant differences were observed between groups in age, sex, follow-up duration, or blood loss; however, the operation time was significantly longer in the CCS (+) group than in the CCS (−) group (P < 0.0001). Radiographic outcomes showed no significant differences in the VWA, CA, AVBH, adjacent vertebral fracture rates, and reoperation rates. However, the incidence of adjacent pedicle screws loosening and pullout was significantly higher in the CCS (−) group than in the CCS (+) group (P = 0.046 and 0.0084, respectively). The correction loss of the CA was significantly lower in the CCS (+) group (CCS (−), 5.6° ± 4.8°; CCS (+), 3.5° ± 4.8°, P = 0.023). The biomechanical test revealed pullout strengths of 683 ± 164, 2231 ± 208, and 3477 ± 393 N for insertion depths of 5, 10, and 15 mm, respectively, with significant increases by depth (P = 0.003 and 0.009).<br>
Conclusions: The CCS technique improves anterior-posterior vertebral body stability, enhances fixation strength, and contributes to better surgical outcomes in OVFs treatment.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841732025A Case of Charcot Spine Arthropathy at the Lumbosacral Level in a Patient With Ankylosis of the Spinee80656ENYoshiakiOdaDepartment of Orthopedic Surgery, Okayama University HospitalKojiUotaniDepartment of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTomokoTetsunagaDepartment of Orthopedic Surgery, Okayama University HospitalKensukeShinoharaDepartment of Orthopedic Surgery, Okayama University HospitalToshifumiOzakiDepartment of Orthopedic Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityCharcot spinal arthropathy, a rare refractory progressive disease, is characterized by symptoms such as pain, deformity, and neurological impairment, which can significantly reduce functional ability, quality of life, and life expectancy. We report a case of Charcot spine at the L5/S1 level with long segment ankylosis to the L5 vertebra. We first performed thorough debridement via a posterior approach. We used antibiotic-containing cement as a spacer to fill the dead space, facilitating the second surgery approach. In the second surgery, transdiscal screws, which have a low profile and strong force, were used as anchors, and bulk bone harvested from both iliac bones was grafted to the intervertebral space. The lumbosacral alignment was kyphotic, and the patient could sit and move independently. Disimpaction was impossible, and a stoma had to be created.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841712025Mid-term Clinical and Radiographic Outcomes of the Actis Total Hip System: A Retrospective Studye77632ENYasutakaMasadaDepartment of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomonoriTetsunagaDepartment of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazukiYamadaDepartment of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiKouraDepartment of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohiroInoueDepartment of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyuichiroOkudaDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokoTetsunagaDepartment of Orthopaedic Surgery, Okayama University HospitalYusukeYokoyamaDepartment of Orthopaedic Surgery, Okayama University HospitalYukiOkazakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshifumiOzakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction<br>
Implant technology for total hip arthroplasty (THA) was developed to improve hip function and patient satisfaction. Actis (DePuy Synthes, Warsaw, IN, USA) is a short fit-and-fill titanium stem, with a medial-collared and triple-taper (MCTT) geometry, that is fully coated with hydroxyapatite (HA). We evaluated the radiographic and clinical outcomes of the Actis Total Hip System during a mean follow-up of five years.<br>
Patients and methods<br>
We retrospectively analyzed data from 80 patients (14 male and 66 female, mean age: 65 ± 8.4 years) who underwent primary THA using Actis stems (anterolateral approach, 60 hips; posterior approach, 20 hips). Radiographs were obtained postoperatively and at the time of the final examination. Radiographic assessments included the alignment of the femoral stem, spot welds, stress shielding, cortical hypertrophy, subsidence (>2 mm), radiolucent line, pedestal formation, Dorr type, canal fill ratio (CFR), and stem fixation. Clinical evaluation included the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ) and Harris Hip Score (HHS).<br>
Results<br>
The mean follow-up period was 64.0 ± 6.0 months. No significant differences were observed in the alignment of the femoral components between approaches. Of the 80 hips, 53 (66.3%) showed radiographic signs of stem osseointegration, predominantly in the mid-distal region of the stem at the final follow-up. Multiple logistic regression analysis revealed that younger age and a higher CFR (20 mm proximal to the lesser trochanter) were associated with the presence of spot welds. Mild stress shielding occurred in 25 hips (31.3%), and no patient experienced severe stress shielding. All stems were fixed by bone on growth. The JHEQ and HHS significantly improved at the final assessment.<br>
Conclusion<br>
At the five-year follow-up, patients who received the Actis Total Hip System during THA had good radiographic and clinical outcomes.<br>No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1434-391614512025Changes in the anatomical positions of the femoral nerve and artery in the lateral and supine positions: a multicenter retrospective study373ENRyuichiroOkudaDepartment of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTomonoriTetsunagaDepartment of Musculoskeletal Health Promotion, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazukiYamadaDepartment of Medical Materials for Musculoskeletal Reconstruction, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokoTetsunagaDepartment of Sports Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiKouraDepartment of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTomohiroInoueDepartment of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasutakaMasadaDepartment of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTetsuyaYamamotoDepartment of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShinMatsumotoDepartment of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHisanoriIkumaDepartment of Orthopaedic Surgery, Kagawa Prefectural Central HospitalTadashiKomatsubaraDepartment of Orthopaedic Surgery, Okayama Rosai HospitalYukiOkazakiDepartment of Orthopaedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToshifumiOzakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction Femoral nerve palsy and femoral artery injury are serious complications of total hip arthroplasty. However, few studies have compared the anatomical positions of these structures in different patient positions. This study aimed to compare the anatomical positions of the femoral nerve and artery in the lateral and supine positions.<br>
Materials and methods This multicenter retrospective study included 111 patients who underwent lateral and supine computed tomography (CT) from 2016 to 2023. CT images were reconstructed in the anterior pelvic plane. The horizontal distance from the anterior margin of the acetabulum to the femoral nerve (Distance N) and femoral artery (Distance A) was measured. The difference in Distance N between the two positions (ΔLateral–supine Distance N) was calculated by subtracting the supine value from the lateral value.<br>
Results The average Distance N was 26.5 ± 5.1 mm in the lateral position and 21.1 ± 4.4 mm in the supine position, with the nerve located significantly closer to the acetabulum in the supine position (P < 0.001). Similarly, the average Distance A was 26.8 ± 5.4 mm in the lateral position and 20.4 ± 4.9 mm in the supine position (P < 0.001). Multiple regression analysis showed that Distance N in the lateral position was significantly shorter in female patients and those with low body weight. In addition, low body weight correlated with a smaller ΔLateral–supine Distance N.<br>
Conclusions The femoral nerve and artery are located closer to the anterior margin of the acetabulum in the supine position than in the lateral position. Low body weight was an independent predictor of shorter Distance N in both positions and a smaller ΔLateral–supine Distance N. These findings underscore the importance of considering patient positioning during total hip arthroplasty, particularly in patients with low body weight, to reduce neurovascular risks.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841742025Subcutaneous and Periorbital Emphysema Following a Dental Proceduree83089ENTakafumiObaraDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama UniversityTsuyoshiNojimaDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama UniversityKazukiNakatsujiDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University HospitalTakashiHongoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama UniversityTetsuyaYumotoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama UniversitySubcutaneous emphysema following dental procedures is rare. We present the case of a young, healthy woman who was transferred from a dental clinic to our emergency department due to sudden swelling of the left orbit immediately after a dental procedure involving the use of the dental air and water syringe. The diagnosis of subcutaneous facial emphysema was made based on the patient's history, physical examination, and computed tomography imaging. The patient received prophylactic amoxicillin, and the lesion resolved completely in one week. Prompt clinical suspicion and a thorough evaluation of the signs and symptoms, including a detailed clinical history, are crucial for diagnosing subcutaneous emphysema following a dental procedure.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1869-695316122025A Multicenter, Prospective, Observational, and Single-Arm Interventional Study of Mirogabalin in Diabetic Peripheral Neuropathic Pain: Rationale and Design of Dia-NeP23512363ENHidekiKamiyaDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of MedicineRyoSuzukiDepartment of Diabetes, Metabolism and Endocrinology, Tokyo Medical UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama UniversityTakahisaDeguchiDepartment of Diabetes, Metabolism and Endocrinology, Kagoshima University Graduate School of Medical and Dental SciencesTatsuhitoHimenoDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of MedicineShuheiYamamotoData Intelligence Department, Daiichi Sankyo Co., Ltd.TaikiToyamaPrimary Medical Science Department, Daiichi Sankyo Co., Ltd.JiroNakamuraDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of MedicineBackground/Objectives: The exact prevalence of and recent changes in diabetic polyneuropathy (DPN) and diabetic peripheral neuropathic pain (DPNP) in Japan are unclear. The oral gabapentinoid, mirogabalin besylate (mirogabalin), is effective with a good safety profile for DPNP with moderate-to-severe pain (numerical rating scale [NRS] scores ≥ 4). However, clinical evidence for mild pain (NRS scores ≤ 3) is unclear. The Dia-NeP study aims to examine: (1) the prevalences of DPN and DPNP and background factors in patients with type 2 diabetes mellitus (T2DM); and (2) the efficacy and safety of mirogabalin in patients with DPNP, including those with mild pain.<br>
Methods: The Dia-NeP study is a multicenter, prospective study consisting of two parts, a baseline survey and an interventional study, to be conducted from March 2025 to August 2026 in patients with T2DM in Japan. The baseline survey is the observational study investigating the epidemiology of DPN and DPNP, and the interventional study is an exploratory, single-arm, open-label study of 12-week mirogabalin treatment. Of patients with T2DM enrolled in the baseline survey, those diagnosed with DPNP who have an NRS score for pain ≥ 1 will be included in the interventional study. The target sample size is 1000 to 3000 patients for the baseline survey and 100 for the interventional study.<br>
Planned Outcomes: The primary endpoint is the change from baseline in the NRS score at week 12 in the interventional study. The safety endpoint is adverse events. This study will not only show the latest prevalence of DPN and DPNP in Japan, but is also the first study to investigate the efficacy and safety of mirogabalin in patients with DPNP having mild pain, as well as moderate-to-severe pain, and is expected to provide useful evidence for future DPN and DPNP treatment.<br>
Trial Registration: Japan Registry of Clinical Trials (jRCTs031240623, registered 20/January/2025, https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031240623).No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Elucidation of puberulic acid–induced nephrotoxicity using stem cell-based kidney organoids42195ENHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesNaruhikoUchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesSoichiroHaraguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesRecent cases of acute kidney injury (AKI) in Japan have been linked to Beni-koji CholesteHelp supplements, with puberulic acid identified as a potential nephrotoxic contaminant. To address the need for a reliable in vitro nephrotoxicity testing platform, we developed a screening model using kidney organoids derived from adult rat kidney stem (KS) cells. The organoids were exposed to known nephrotoxicants, including cisplatin and gentamicin, to validate the system. Puberulic acid toxicity was evaluated in both KS cell-derived organoids and wild-type mice. The organoids recapitulated tubular injury induced by known nephrotoxins and showed significant Kim-1 mRNA upregulation. Puberulic acid-treated organoids and mice exhibited morphological features of acute tubular necrosis (ATN), mitochondrial damage, and reduced cytochrome c oxidase subunit IV (COX-IV) expression. Markers of oxidative stress and apoptosis, such as 8-hydroxy-2’-deoxyguanosine (8-OHdG) and cleaved caspase-3, were also elevated. These findings suggest that puberulic acid induces mitochondrial dysfunction and oxidative stress, leading to tubular cell death. Puberulic acid-induced nephrotoxicity was demonstrated using our kidney organoid model. KS cell-derived kidney organoids may provide a simple, reproducible, and rapid platform for nephrotoxicity assessment, which may complement conventional animal experiments.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0916-963648112025Efficacy and safety of esaxerenone with and without sodium–glucose cotransporter-2 inhibitor use in hypertensive patients with type 2 diabetes mellitus: a pooled analysis of five clinical studies29242937ENHirohikoMotokiDepartment of Cardiovascular Medicine, Shinshu University School of MedicineKoichiroKuwaharaDepartment of Cardiovascular Medicine, Shinshu University School of MedicineHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKazuomiKarioDivision of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of MedicineTomohiroKatsuyaKatsuya ClinicTatsuoShimosawaDepartment of Clinical Laboratory, School of Medicine, International University of Health and WelfareKenichiTsujitaDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto UniversityShokoSuzukiData Intelligence Department, Daiichi Sankyo Co. Ltd.TomohiroSuedomiPrimary Medical Science Department, Daiichi Sankyo Co. Ltd.TakashiTaguchiPrimary Medical Science Department, Daiichi Sankyo Co. Ltd.This pooled subanalysis of five multicenter, prospective, open-label, single-arm studies on esaxerenone aimed to evaluate the efficacy, organ-protective effects, and safety of esaxerenone in hypertensive patients with type 2 diabetes mellitus (T2DM), with and without concomitant sodium–glucose cotransporter-2 inhibitor (SGLT2i) therapy. In total, 283 and 279 patients were included in the safety (with SGLT2i, 148; without, 135) and full analysis sets (with SGLT2i; 145; without, 134), respectively. Significant changes in morning home systolic/diastolic blood pressure (SBP/DBP) from baseline to Week 12 were shown in the overall population (mean change: −11.9/−5.2 mmHg, both P < 0.001) and both SGLT2i and non-SGLT2i subgroups (−11.3/−4.8 and −12.5/−5.7 mmHg, respectively, all P < 0.001). Similar findings were observed in bedtime home and office SBP/DBP. The proportions of patients who achieved target home SBP/DBP < 135/85 mmHg were 71.2% (overall population) and 70.5% and 71.9% in the SGLT2i and non-SGLT2i subgroups, respectively. The urine albumin-to-creatinine ratio significantly improved from baseline to Week 12 in the overall population and SGLT2i subgroups (percentage change in geometric mean from baseline: −42.8%, −43.0%, and −42.6%, respectively, all P < 0.001). N-terminal pro-B-type natriuretic peptide levels improved in all groups. The incidence of serum potassium ≥5.5 mEq/L was 2.0% vs 5.2% in the SGLT2i vs non-SGLT2i subgroups. Esaxerenone demonstrated significant BP-lowering effects, and improved renal and cardiovascular parameters, regardless of SGLT2i use. Safety was consistent across groups, with the numerically lower incidence of serum potassium ≥5.5 mEq/L in the SGLT2i subgroup suggesting a potential mitigating effect of SGLT2is on the risk of hyperkalemia.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1342-175129102025First-time diagnosis and referral practices for individuals with CKD by primary care physicians: a study of electronic medical records across multiple clinics in Japan13421353ENHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYujiNagaoMedicine Division, Nippon Boehringer Ingelheim Co., Ltd.KatsuhitoIharaMedicine Division, Nippon Boehringer Ingelheim Co., Ltd.Background Chronic kidney disease (CKD) is a major public health burden in Japan. Japanese primary care physicians (PCPs) are expected to play an important role in the early diagnosis and management of CKD, but comprehensive data on their role are limited.<br>
Methods This observational study examined data from individuals who underwent tests for CKD diagnosis between January 2017 and September 2023 in the Japan Medical Data Survey (JAMDAS) database of primary care clinics in Japan. The primary outcome was the proportion of individuals with CKD without the registration of a CKD-related disease code. Time to CKD diagnosis and referral were also assessed.<br>
Results Among 1,188,543 eligible individuals who underwent kidney-related laboratory tests, 183,473 (15.4%) met CKD diagnosis criteria according to the Japanese Clinical Practice Guideline for CKD. The mean (± SD) age was 77.4 ± 11.0 years, 57.1% were female, and 71.8% had CKD stage 3a. Over 98% of individuals who met CKD diagnosis criteria did not receive an insurance diagnosis code within 90 days after meeting the criteria. Among referrable individuals, 89.7% did not receive a referral within 90 days of meeting the referral criteria.<br>
Conclusion These results suggest CKD may be underdiagnosed and under-referred in Japanese clinics. Measures should be taken to increase detection and diagnosis according to the Japanese Clinical Practice Guideline for CKD.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0916-96364892025Efficacy and safety of esaxerenone in hypertensive patients with chronic kidney disease, with or without type 2 diabetes mellitus: a pooled analysis of five clinical studies24132426ENHaruhito A.UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHirohikoMotokiDepartment of Cardiovascular Medicine, Shinshu University School of MedicineKoichiroKuwaharaDepartment of Cardiovascular Medicine, Shinshu University School of MedicineKazuomiKarioDivision of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of MedicineTomohiroKatsuyaKatsuya ClinicTatsuoShimosawaDepartment of Clinical Laboratory, School of Medicine, International University of Health and WelfareKenichiTsujitaDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto UniversityShokoSuzukiData Intelligence Department, Daiichi Sankyo Co., Ltd.TomohiroSuedomiPrimary Medical Science Department, Daiichi Sankyo Co., Ltd.TakashiTaguchiPrimary Medical Science Department, Daiichi Sankyo Co., Ltd.Effective management of blood pressure (BP) and albuminuria are crucial for suppressing chronic kidney disease (CKD) progression and cardiovascular risks in hypertension. This pooled analysis evaluated the antihypertensive effects, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD by integrating five clinical studies of esaxerenone. Patients were divided based on type 2 diabetes mellitus (T2DM) status (with or without T2DM) and creatinine-based estimated glomerular filtration rate (eGFRcreat) (30 to <60 and ≥60 mL/min/1.73 m2). Significant changes in morning home BP from baseline at Week 12 were observed in the overall population (mean change −12.8/ − 5.4 mmHg), T2DM subgroups ( − 12.2/ − 4.5 and −14.5/ − 7.8 mmHg), and eGFRcreat subgroups ( − 12.5/ − 4.7 and −14.0/ − 6.9 mmHg) (all P < 0.001). Bedtime home and office BP showed similar tendencies. Urine albumin-to-creatinine ratio significantly improved from baseline at Week 12 in the overall population (mean change: −55.2%), T2DM subgroups ( − 56.5% and −52.0%), and eGFRcreat subgroups ( − 54.6% and −55.4%) (all P < 0.001). N-terminal pro-B-type natriuretic peptide levels significantly decreased in the overall population (percent change: −14.1%) and subgroup without T2DM ( − 25.3%). The incidence of serum potassium ≥5.5 mEq/L was lower in the subgroup with T2DM vs without T2DM (3.1% and 11.3%), potentially related to the use of sodium–glucose cotransporter 2 inhibitors. These findings highlight the sustained BP-lowering effect of esaxerenone throughout the day in hypertensive patients with CKD, irrespective of T2DM status, and its significant reduction in albuminuria. The data support the safety and efficacy of esaxerenone in this patient population, underscoring its potential as a valuable therapeutic option.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients5762ENYoshiyasuTonguTohoku University School of MedicineTomokoKasaharaDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineYasutoshiAkiyamaLaboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical SciencesTakehiroSuzukiDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineHsin-JungHoDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineYotaroMatsumotoLaboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical SciencesRyotaKujiraiLaboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical SciencesKoichiKikuchiDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineKojiNataDepartment of Medical Biochemistry, School of Pharmacy, Iwate Medical UniversityMakotoKanzakiDepartment of Biomedical Engineering, Tohoku UniversityKenshinSuzukiTohoku University School of MedicineShunWatanabeDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineChiharuKawabeDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineYuiMiyataDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineShunItaiDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineTakafumiToyoharaDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineChitoseSuzukiDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicineTetsuhiroTanakaDivision of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of MedicineJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaTomiokaLaboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical SciencesTakaakiAbeDepartment of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of MedicinePatients with end-stage renal disease have lower fasting plasma glucose and HbA1c levels, with significantly higher insulin levels. For a long time, it has been believed that this higher insulin level in renal failure is due to decreased insulin clearance caused by reduced renal function. However, here we reported that accumulation of the gut microbiota-derived uremic toxin, phenyl sulfate (PS) in the renal failure, increased insulin secretion from the pancreas by enhanced glucose-stimulated insulin secretion. Other endogenous sulfides compounds which accumulated as in the renal failure also increased glucose-stimulated insulin secretion from β-cell. With RNA-seq analyses and gene knock down, we demonstrated that insulin secretion evoked by PS was mediated by Ddah2. In addition, we also found that PS increased insulin resistance through lncRNA expression and Erk phosphorylation in the adipocytes. To confirm the relationship between PS and glucose metabolism in human, we recruited 2 clinical cohort studies (DKD and CKD) including 462 patients, and found that there was a weak negative correlation between PS and HbA1c. Because these trials did not measure fasting insulin level, we alternatively used the urinary C-peptide/creatinine ratio (UCPCR) as an indicator of insulin resistance. We found that PS may induce insulin resistance in patients with eGFR < 60 mL/min/1.73 m2. These data suggest that the accumulation of uremic toxins modulates glucose metabolism and induced insulin resistance in CKD and DKD patients. Considering HbA1c as a reflection of chronic hyperglycemia and UCPCR as a reflection of chronic hyperinsulinemia, our findings indicate that PS is negatively associated with hyperglycemia independent of CKD, and positively associated with hyperinsulinemia in DKD patients.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221412024Association between proteinuria and mineral metabolism disorders in chronic kidney disease: the Japan chronic kidney disease database extension (J-CKD-DB-Ex)27481ENShoShimamotoDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityTakakoNakaharaDepartment of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical WelfareShunsukeYamadaDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityHajimeNagasuDepartment of Nephrology and Hypertension, Kawasaki Medical SchoolSeijiKishiDepartment of Nephrology and Hypertension, Kawasaki Medical SchoolNaokiNakashimaDepartment of Medical Informatics, Graduate School of Medical Science, Kyushu UniversityKazuhikoTsuruyaDepartment of Nephrology, Nara Medical UniversityHirokazuOkadaDepartment of Nephrology, Faculty of Medicine, Saitama Medical UniversityKouichiTamuraDepartment of Medical Science and Cardiorenal Medicine, Graduate School of Medicine, Yokohama City UniversityIchieiNaritaDivision of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental SciencesShoichiMaruyamaDepartment of Nephrology, Nagoya University Graduate School of MedicineYuichiroYanoDepartment of General Medicine, Juntendo University Faculty of MedicineTakashiYokooDivision of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of MedicineTakashiWadaDepartment of Nephrology and Rheumatology, Kanazawa UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineEiichiroKandaDepartment of Health Data Science, Kawasaki Medical SchoolHiromiKataokaDepartment of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical WelfareMasaomiNangakuDivision of Nephrology and Endocrinology, University of Tokyo Graduate School of MedicineNaokiKashiharaDepartment of Nephrology and Hypertension, Kawasaki Medical SchoolToshiakiNakanoDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityChronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0929-19032025p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosisENTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuoNagaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinoriKajiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoyukiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeTakahashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiakiOharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyoshi Y.TanakaDepartment of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health SystemsMitsunobu R.KanoDepartment of Pharmaceutical Biomedicine, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health SystemsAtsushiMasamuneDivision of Gastroenterology, Tohoku University Graduate School of MedicineYasuoUrataOncolys BioPharma, Inc.ShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPancreatic ductal adenocarcinoma (PDAC)-associated pancreatic stellate cells (PSCs) promote PDAC tumor progression. Notably, PDAC tumors display enhanced macropinocytosis, resulting in enhanced uptake of extracellular particles, including nutrients and viruses. We previously demonstrated the therapeutic potential of telomerase-specific oncolytic adenoviruses OBP-301 and p53-armed OBP-702 against human PDAC cells. However, it remains unclear whether macropinocytosis promotes the virus sensitivity of PDAC-associated PSCs. Here, we show that PSCs activated by human PDAC cells (Panc-1 and BxPC-3) exhibit enhanced sensitivity to wild-type and oncolytic adenoviruses via enhanced macropinocytosis. The virus sensitivity of PSCs was analyzed for the infectivity, replication, and cytopathic activity of wild-type and oncolytic adenoviruses. PDAC-associated PSCs were more sensitive to wild-type and oncolytic adenoviruses than were control PSCs; this sensitivity was mediated by activation of macropinocytosis. In three-dimensional (3D) culture models, p53-armed OBP-702 decreased the viability of PDAC-associated PSCs more strongly than did non-armed OBP-301, reflecting induction of p53-mediated apoptosis. Co-inoculation of PSCs enhanced the growth of PDAC tumors, an effect that was attenuated by OBP-702-mediated p53 activation in the tumor stroma. Our results suggest that p53-armed oncolytic adenovirus OBP-702 eliminates PDAC-associated PSCs via enhancement of macropinocytosis-mediated virus entry and induction of p53-mediated apoptosis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417102025Bladder Trigone as a Sensory Hub: A Narrative Reviewe94951ENTakuyaSadahiraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiMaruyamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYosukeMitsuiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakanoriSekitoDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomofumiWatanabeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasamiWatanabeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe bladder trigone is an anatomically and functionally distinct region within the lower urinary tract (LUT), characterized by a dense network of afferent sensory fibers, specialized urothelial interactions, and prominent mechanotransduction mechanisms. Its intricate neuroarchitecture enables precise detection of bladder filling and coordination of micturition, whereas dysregulation of these pathways contributes to lower urinary tract symptoms (LUTS), including urgency, frequency, and bladder pain. Despite its recognized clinical relevance, the structural and functional basis of trigonal sensory signaling - and its role - remain incompletely understood.<br>
This review synthesizes current evidence on trigonal afferent organization, integrating data from anatomical mapping, receptor profiling, electrophysiological characterization, and translational research. Seminal anatomical observations are combined with recent advances in mechanotransduction and purinergic, peptidergic, and transient receptor potential (TRP) signaling to provide a comprehensive perspective. The trigone exhibits three principal afferent classes: (1) intraepithelial fibers penetrating umbrella cells, marked by P2X purinoceptor 3 (P2X3), transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP), and substance P (SP); (2) subepithelial plexuses surrounding microvasculature, enriched in vasoactive neuropeptides and exhibiting plastic hypertrophy in overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS); and (3) encapsulated corpuscular endings at the lamina propria-detrusor junction, expressing PIEZO1/2 and acid-sensing ion channels (ASICs) for rapid adaptation. In trigeminal dorsal root ganglion (DRG) neurons, high expression of PIEZO2, P2RX3, and voltage-gated sodium channel, type 1.8 (Nav1.8) was observed, revealing their role as the foundation for multisensory information processing. Functional assays highlight distinct mechanotransductive and chemosensory pathways, with aging, inflammation, and neurotrophic factors driving afferent plasticity underlying abnormal bladder sensation, such as urgency, frequency, and pain. Early clinical trials of P2X3 antagonists and intravesical TRPV1 inhibitors demonstrate promising symptomatic benefits. Collectively, evidence positions the bladder trigone as a critical sensory hub where neuronal, urothelial, and immune signals converge to regulate bladder sensation. Understanding its molecular and structural specialization may inform the development of region-specific neuromodulatory therapies targeting sensory urgency and afferent-driven bladder dysfunction.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0927-59403262025Beneficial fiscal competition for foreign direct investment: transport infrastructure and economic integration18391864ENShigeoMoritaFaculty of Economics, Fukuoka UniversityHirofumiOkoshiFaculty of Economics, Okayama UniversityFiscal policy competition for a multinational enterprise (MNE) resulting in the same location of firms is widely recognized as harmful owing to losses of the host government’s budget without gains from firms’ behavior. In this study, we provide a plausible explanation why fiscal competition for an MNE keeping firms’ location choices unchanged can be beneficial by incorporating governments’ decisions on public investments in transport infrastructure, such as ports, which reduces the trade costs between two competing countries. Our model divides transport costs into infrastructure-independent and infrastructure-dependent; investments in infrastructure reduce infrastructure-dependent costs. We show that fiscal competition increases countries’ investments in infrastructure under low infrastructure-independent transport costs without affecting firms’ locations. Furthermore, we show that the host country benefits from fiscal competition, although it pays a subsidy to the MNE. Moreover, as investments in infrastructure generate positive spillovers, fiscal competition that improves transport infrastructure benefits non-host countries and improves global welfare.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-13801812025Tattoo-associated toxic shock syndrome: a case report185ENTakuyaKuboDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityBackground: Toxic shock syndrome (TSS) is a rare but life-threatening complication occasionally reported after tattooing.<br>
Case presentation: : A 29-year-old Japanese man was admitted to Okayama University Hospital, Okayama, Japan, in early spring 2025, one week after receiving a tattoo on his right shoulder and upper arm in Osaka. He presented with fever, gastrointestinal symptoms, hypotension, and multi-organ failure. Despite a failure to isolate a causative pathogen, he met clinical criteria for TSS. Supportive care and broad-spectrum antibiotics led to full recovery.<br>
Conclusions: TSS can occur after tattooing, even in individuals without apparent immunodeficiency. Pathogenic organisms may be unidentifiable; however, clinical diagnosis should not be delayed, and early therapeutic interventions are essential to improve outcomes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0925-571012252025Cytomegalovirus reactivation in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy689699ENKentaHayashinoDepartment of Hematology and Oncology, Okayama UniversityKeisukeSeikeDepartment of Hematology and Oncology, Okayama UniversityTaroMasunariDepartment of Hematology, Chugoku Central HospitalRisaHashidaDivision of Hematology, Ehime Prefectural Central HospitalSatoshiOkaDepartment of Hematology and Blood Transfusion, Kochi Health Science CenterYukiFujiwaraDepartment of Hematology and Oncology, Japanese Red Cross Society Himeji HospitalToshikiTeraoDepartment of Hematology and Oncology, Okayama UniversityWataruKitamuraDepartment of Hematology and Oncology, Okayama UniversityHirokiKobayashiDepartment of Hematology and Oncology, Okayama UniversityChihiroKamoiDepartment of Hematology and Oncology, Okayama UniversityTakumiKondoDepartment of Hematology and Oncology, Okayama UniversityHideakiFujiwaraDepartment of Hematology and Oncology, Okayama UniversityNoboruAsadaDepartment of Hematology and Oncology, Okayama UniversityDaisukeEnnishiDepartment of Hematology and Oncology, Okayama UniversityKeikoFujiiDepartment of Hematology and Oncology, Okayama UniversityNobuharuFujiiDepartment of Hematology and Oncology, Okayama UniversityYoshinobuMaedaDepartment of Hematology and Oncology, Okayama UniversityChimeric antigen receptor (CAR) T-cell therapy has improved outcomes of relapsed and/or refractory large B-cell lymphoma (r/r LBCL). However, its off-tumor effects result in severe prolonged humoral immune deficiency. Cytomegalovirus (CMV) is a latent virus that can be life-threatening in immunosuppressed patients. In the setting of CAR T-cell therapy, Asian race is a risk factor for clinically significant CMV infection. However, the effect of CAR T-cell therapy on CMV reactivation in Japanese patients remains unclear. Previous reports used polymerase chain reaction (PCR), but we used the pp65 antigenemia assay to retrospectively investigate long-term effects in patients with r/r LBCL. The study included 46 patients. Nine (19.6%) developed CMV reactivation, with a median onset of 13 days. Six of these patients received preemptive therapy, and none developed CMV end-organ disease. Primary refractory disease, grade 2–4 cytokine release syndrome, and high-dose corticosteroids were risk factors for CMV reactivation. Long-term follow-up showed that CMV reactivation rarely occurred later than 28 days post-infusion. Our study using the pp65 antigenemia assay showed a similar incidence of CMV reactivation, onset, and risk factors to those in the previous reports using PCR.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96252025Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancerENKohjiTanakayaDepartment of Surgery, National Hospital Organization Iwakuni Clinical CenterTatsuroYamaguchiDepartment of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalKeijiHirataDepartment of Surgery 1, University of Occupational and Environmental HealthMasayoshiYamadaEndoscopy Division, National Cancer Center HospitalKensukeKumamotoDepartment of Genome Medical Science and Medical Genetics, Faculty of Medicine, Kagawa UniversityYasukiAkiyamaDepartment of Surgery 1, University of Occupational and Environmental HealthKeiIshimaruDivision of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime UniversityKoichiOkamotoDepartment of Gastroenterology and Oncology, Tokushima University Graduate School of Medical ScienceYukoKawasakiCollege of Nursing, University of HyogoKeigoKomineDepartment of Medical Oncology, Tohoku University HospitalAkiraSakamotoDepartment of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshikoShibataHimawari-No-Kai (Sunflower Association), a Patient Advocacy Group for Individuals and Families Affected By Lynch SyndromeYusakuShimamotoDivision of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of MedicineHidekiShimodairaDivision of Medical Oncology, Faculty of Medicine, Tohoku Medical and Pharmaceutical UniversityShigekiSekineDepartment of Pathology, Keio University School of MedicineAkinariTakaoDepartment of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalMisatoTakaoDepartment of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalYasuyukiTakamizawaDepartment of Colorectal Surgery, National Cancer Center HospitalYojiTakeuchiDepartment of Gastroenterology and Hepatology, Gunma University Graduate School of MedicineNorikoTanabeDepartment of Clinical Genetics, Saitama Medical Center, Saitama Medical UniversityFumitakaTaniguchiDepartment of Surgery, Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens HospitalAkikoChinoDepartment of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchHourinChoEndoscopy Center, Tokyo Medical University HospitalSatoruDoiHarmony Line (Association for Patients and Families With Familial Adenomatous Polyposis)TakeshiNakajimaDivision of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer InstituteSakikoNakamoriDepartment of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalYoshikoNakayamaDepartment of Pediatrics, Shinshu University School of MedicineToshiyaNagasakiDepartment of Gastroenterological Surgery, Saitama Cancer CenterHisashiHasumiDepartment of Urology, Yokohama City UniversityKoujiBannoCenter of Maternal -Fetal/Neonatal Medicine, Hiroshima University HospitalTakaoHinoiDepartment of Clinical and Molecular Genetics, Hiroshima University HospitalKenjiFujiyoshiDepartment of Surgery, Kurume University School of MedicineTakahiroHorimatsuInstitute for Advancement of Clinical and Translational Science, Kyoto University HospitalKentaMasudaDepartment of Obstetrics and Gynecology, Keio University School of MedicineMasashiMiguchiDepartment of Gastroenterological Surgery, Hiroshima Prefectural HospitalYusukeMizuuchiDepartment of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu UniversityYasuyukiMiyakuraDepartment of Colon and Pelvic Surgery, Cancer Prevention and Genetic Counseling, Tochigi Cancer CenterMichihiroMutohDepartment of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of MedicineTakahiroYoshiokaDepartment of Gastroenterological Surgery, Kochi Health Sciences CenterShinjiTanakaJA Onomichi General HospitalKazuhiroSakamotoKoshigaya Municipal HospitalKentaroSakamakiFaculty of Health Data Science, Juntendo UniversityMichioItabashiSaiseikai Kazo HospitalHideyukiIshidaDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical UniversityNaohiroTomitaDivision of Cancer Treatment , Toyonaka Municipal HospitalKenichiSugiharaInstitute of Science TokyoYoichiAjiokaDivision of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata UniversityApproximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1436-32912862025Gallbladder edema as a clue to zolbetuximab-associated protein-losing enteropathy in gastric cancer: a case report12971301ENYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShinjiKurodaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShunyaHanzawaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNobuhikoKanayaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHajimeKashimaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSatoruKikuchiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYoshiyasuKonoDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShunsukeKagawaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineWe report a rare case of protein-losing enteropathy (PLE) during zolbetuximab treatment in a 73-year-old woman with Stage IVB gastric cancer. After chemo-immunotherapy and curative surgery, 3rd-line treatment with capecitabine, oxaliplatin, and zolbetuximab was initiated due to recurrence. The patient developed persistent right upper abdominal pain; imaging revealed gallbladder wall edema, followed by mild gastric wall edema, despite unremarkable laboratory findings. Protein-losing scintigraphy demonstrated abnormal gastric protein leakage, leading to a diagnosis of PLE. While gastrointestinal toxicity is known with zolbetuximab, this is, to our knowledge, the first clinically diagnosed case of PLE in which gallbladder edema served as a diagnostic clue. As treatment strategies for advanced gastric cancer grow increasingly complex, achieving maximum therapeutic benefit requires not only optimal drug selection but also timely recognition and management of adverse events. With the broader use of zolbetuximab, clinicians should be mindful of this rare but potentially significant complication.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417112025Long-Term Outcome of Xenon-Arc Photocoagulation for Retinopathy of Prematurity in the 1970s in Japan: Eleven Patients With 32- to 49-Year Follow-Upe97797ENToshihikoMatsuoHealthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNobuhikoMatsuoOphthalmology, Okayama University Medical SchoolObjectives: Photocoagulation or cryocautery, or their combinations, are the standard of care for retinopathy of prematurity at the recommended timing, which is based on the International Classification of Retinopathy of Prematurity. In Japan, the effectiveness of xenon-arc photocoagulation and cryocautery in retinopathy of prematurity was reported on an empirical basis first in 1968, and became the standard of care in retinopathy of prematurity in the 1970s, 10 years earlier compared with the other countries. In this study, we reported the up to 49 years visual outcome of 11 patients with retinopathy of prematurity who underwent xenon-arc photocoagulation and cryocautery in the 1970s.<br>
Methods: A retrospective review was made on the medical records of 11 consecutive patients who underwent xenon-arc photocoagulation for retinopathy of prematurity in the years 1974 to 1980, and were followed up until the period from 2009 to 2025. The birthweight ranged from 865 g to 2300 g at a median of 1350 g, and the gestational age at birth ranged from 27 weeks to 36 weeks at a median of 30 weeks. The corrected gestational age at the time of photocoagulation ranged from 32 weeks to 53 weeks, with a median of 37 weeks. Oxygen was given to all 11 patients, except for one who was born in the earliest year 1974. The retinopathy of prematurity was at stage 3 in both eyes of seven patients, with plus disease signs in four patients, at stage 2 with and without plus disease in two patients, at stage 2 and stage 3 in each eye of one patient, and at stage 1 with plus disease in both eyes of one patient. The entire 360-degree photocoagulation was given in seven patients, while partial photocoagulation was applied in four patients. Additional cryocautery was applied in six patients.<br>
Results: The age at the last visit ranged from 32 to 49 years with a median of 46 years. At the last visit, seven patients showed the best-corrected visual acuity in decimals of 0.8 or better in both eyes. One dizygotic twin showed no light perception in the phthisic right eye and 0.1 in the left eye with macular degeneration and nystagmus after he underwent cataract surgery at the age of 34 years. The other twin had the best-corrected visual acuity of 0.5 in the right eye and 0.02 in the left eye due to macular degeneration after he underwent cataract surgeries in both eyes at the age of 36 years. Two patients developed rhegmatogenous retinal detachment in one eye at the age of 44 and 41 years, respectively, and underwent vitrectomy with silicone oil tamponade, resulting in visual acuity of 0.1 and 0.3, respectively. Two patients experienced vitreous hemorrhage in one eye, which was absorbed spontaneously at the ages of 37 years and 42 years, respectively. One patient underwent partial scleral buckling for localized rhegmatogenous retinal detachment. No patient used intraocular pressure-lowering eyedrops.<br>
Conclusion: Most patients with xenon-arc photocoagulation for retinopathy of prematurity in the 1970s maintained standard levels of visual acuity up to 49 years in the follow-up. Cataract, retinal detachment, and vitreous hemorrhage were noted as late complications and were coped with on an individual basis. The conclusion would have a meaning, even though not novel, that the patients with retinopathy of prematurity would have benefited from the xenon-arc photocoagulation and cryocautery.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-230X2512025Neoadjuvant chemotherapy strategies for optimizing safety and efficacy in elderly patients with locally advanced gastric cancer670ENYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShinjiKurodaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShunyaHanzawaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNobuhikoKanayaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHajimeKashimaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSatoruKikuchiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShunsukeKagawaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineBackground The completion rate of adjuvant chemotherapy for gastric cancer (GC) is suboptimal, particularly in elderly patients. While neoadjuvant chemotherapy (NAC) for locally advanced GC has shown promise, data on elderly patients remain limited. Given the considerable physical burden of NAC, optimizing its administration is crucial. This study evaluates the safety and efficacy of a modified approach for elderly patients.<br>
Methods A retrospective analysis was conducted on 38 patients with cStage II/III GC who received NAC between November 2015 and December 2023. Additionally, 25 patients aged ≥ 75 years with cStage III who underwent upfront surgery during the same period were analyzed.<br>
Results The NAC group was divided into non-elderly (< 75 years, n = 27) and elderly (≥ 75 years, n = 11) groups. The elderly group had poorer ECOG-PS (p = 0.016). While all non-elderly patients completed ≤ 3 cycles, more elderly patients underwent 4 cycles (p = 0.0047). However, per-cycles of S-1 (p = 0.0003) and oxaliplatin (p = 0.0018) were lower in the elderly group. Importantly, adverse events and treatment efficacy were comparable between groups. Among patients aged ≥ 75 years, the upfront surgery group had poorer ECOG-PS (p = 0.017) and underwent more frequent distal gastrectomy (p = 0.014).<br>
Conclusions NAC can be safely administered to elderly patients by increasing cycles while reducing per-cycle dosage. It may also serve as a viable alternative to upfront surgery.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2399-3669812025Synthesis of thienoacenes by electrochemical double C–S cyclization using a halogen mediator366ENKoichiMitsudoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTakuyaNagaharaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNozomiKatauraDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYukaOkamuraDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTokiYonezawaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYuriTachibanaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNolanSouliéFaculty of Science and Engineering, Sorbonne UniversitéKeisukeShigemoriDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityEisukeSatoDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHirokiMandaiDepartment of Pharmacy, Faculty of Pharmacy, Gifu University of Medical ScienceSeijiSugaDivision of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThienoacenes are significant compounds as organic materials. One of the most efficient ways to synthesize thienoacenes is to form multiple C–S bonds in a single step. Because unprotected S–H bonds are easily oxidized to S–S bonds, S-Me protected substrates are commonly used for the purpose. However, their reactivity is insufficient, and one-step construction of multiple C–S bonds is still challenging. We herein report the electrochemical synthesis of thienoacenes from S-methoxymethyl (MOM)-protected diarylacetylenes. In the presence of Bu4NBr as a halogen mediator, electrochemical double C–S cyclization of diarylacetylenes bearing two MOM groups proceeded to afford [1]benzothieno[3,2-b][1]benzothiophene (BTBT) derivatives. While S-Me or S-p-methoxybenzyl (PMB)-protected diarylacetylenes did not afford BTBT, BTBT was selectively obtained when a substrate protected with S-MOM groups was used. The S-MOM protection strategy is also effective for the electrochemical synthesis of a more π-expanded thienoacene such as dibenzo[d,d′]thieno[3,2-b,4,5-b′]dithiophene (DBTDT).No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2662-47292025Evaluation of the small-field output factor in eclipse modeling methods using representative beam and measured data with averaged ionization chamber and diode detector measurementsENKunioNishiokaDepartment of Radiology, Tokuyama Central HospitalYukiKuniiDepartment of Radiology, Tokuyama Central HospitalYoshinoriTanabeDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityYuichiSakamotoDepartment of Radiology, Tokuyama Central HospitalAkiraNakamotoDepartment of Radiology, Tokuyama Central HospitalShotaroTakahashiDepartment of Radiology, Tokuyama Central HospitalBeam modeling for radiotherapy treatment planning systems (RTPS) can be performed using representative beam data (RBD) or direct measurements. However, RBD typically excludes output factor (OPF) measurements for fields smaller than 3 × 3 cm2. The Eclipse treatment planning system addresses this limitation by incorporating measured OPF data for fields as small as 1 × 1 cm2. Although existing studies have primarily examined the accuracy of small-field OPFs for plastic scintillator detectors, studies directly comparing the OPF values obtained through RBD modeling with and without OPF measurements for small field sizes are limited. Therefore, this study proposes a novel measurement approach using data averaged from an ion chamber and diode detector for small-field dosimetry to provide critical insights into the integration of OPFs for these small field sizes in RBD-based beam modeling. We systematically evaluated the impact of small-field OPF measurements on beam modeling accuracy by comparing three distinct approaches: (1) RBD-based modeling without small-field OPF data, (2) RBD-based modeling incorporating measured small-field OPF data, and (3) modeling based solely on measured data, with and without the inclusion of 1 × 1 cm2 field sizes. In addition, we compared OPF values obtained from a W2 plastic scintillator detector with the averaged OPF values from a PinPoint 3D ion chamber and EDGE diode detector across multiple beam energies and flattening filter-free (FFF) configurations. Our analysis included field sizes ranging from 1 × 1 cm2 to 40 × 40 cm2. The results demonstrated that for square fields, OPF calculation differences between RBD modeling with and without measured data were < 1.5%, < 4.5%, and < 4.5% at 1 × 1 cm2, and < 0.5%, < 1.5%, and < 1.5% at 2 × 2 cm2, respectively. The RBD group exhibited a trend in which the OPF difference increased with the expansion of the irradiation field size. Notably, the most significant variations between modeling approaches occurred along the upper jaw expansion direction in rectangular fields. This suggests that a thorough evaluation is necessary for modeling results with an OPF ≤ 1 × 1 cm2. This study highlights the advantages and disadvantages of beam modeling using measured OPF and RBD, providing valuable insights for future facilities that rely solely on RBD for beam modeling.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1279-85174712025A case of a large venous ring around the mandibular condyle95ENKeitaroNishiDepartment of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima UniversityTatsuoOkuiDepartment of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima UniversityYoheiTakeshitaDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJingoKusukawaDental and Oral Medical Center, Kurume University School of MedicineR. ShaneTubbsDepartment of Neurosurgery, Clinical Neuroscience Research Center, Tulane University School of MedicineJoeIwanagaDental and Oral Medical Center, Kurume University School of MedicineAnatomical details regarding venous drainage of the head and neck are an important matter for surgeons to avoid unnecessary complications such as hemorrhage. This report describes a case of the large venous ring around the mandibular condyle found in the cadaver. The left maxillofacial region of a latex-injected embalmed male cadaver (82 years of age at death) was dissected. The large two maxillary veins ran lateral to the capsule and superior to the mandibular notch and coursed posteroinferiorly to merge, and one trunk was formed at the posterior border of the ramus. It then received the superficial temporal vein superiorly to form the retromandibular vein (RMV). In addition, three maxillary veins were drained from the pterygoid venous plexus (PVP), medial to the ramus, one maxillary vein drained from the PVP into the RMV trunk, while two maxillary veins drained from the PVP into the anterior division of the RMV. All five large veins lateral and medial to the condyle drained from the PVP into the RMV. The knowledge of such an anatomical variation might prevent intraoperative bleeding in the temporomandibular joint region.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1618-12472025Impact of CT-assessed sarcopenia on the severity of odontogenic deep neck infections: a retrospective cohort studyENShogoKikutaDental and Oral Medical Center, Kurume University School of MedicineEijiIwataDepartment of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYoheiTakeshitaDepartment of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineChizuruKobayashiDepartment of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHirokiKimuraDepartment of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYukiKinisadaDepartment of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineAkiraTachibanaDepartment of Oral and Maxillofacial Surgery, Kakogawa Central City HospitalJingoKusukawaDental and Oral Medical Center, Kurume University School of MedicineMasayaAkashiDepartment of Oral and Maxillofacial Surgery, Kobe University Graduate School of MedicineSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSarcopenia is increasingly recognized as a key predictor of adverse health outcomes. This study aimed to evaluate the impact of computed tomography-assessed sarcopenia (CT–SP) on the clinical severity and hospitalization duration of odontogenic deep neck infections (DNIs). Total of 119 patients admitted for odontogenic DNI treatment were included. Patients were divided into two groups by DNI clinical severity (severe or mild) and the patients' characteristics, including CT–SP based on skeletal muscle index (SMI), were compared between two groups. Multivariable logistic regression analysis was performed to identify independent risk factors for severe DNI. The correlation between SMI and hospitalization duration was assessed using Spearman’s rank correlation coefficient. Of the 119 patients, 60 (50.4%) presented with severe DNIs, including deep neck abscesses and necrotizing soft tissue infections. After adjusting for potential confounders, multivariable analysis identified CT–SP as the sole independent risk factor associated with severe DNI (Odds Ratio = 3.04; 95% Confidence Interval, 1.20–7.71; p = 0.019). Furthermore, SMI demonstrated a significant, weak negative correlation with the hospitalization duration (r = − 0.331, p < 0.001). CT–SP is a powerful, independent risk factor associated with severity in patients with odontogenic DNIs. This finding underscores the critical role of systemic host factors in the clinical course of maxillofacial infections and highlights the potential of opportunistic CT screening as a factor to consider in risk stratification in this vulnerable population.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2211-16622025Performance Assessment of ChatGPT for the Board Qualification Examination of the Japanese Society for Oral and Maxillofacial RadiologyENYoheiTakeshitaDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiyukiKawazuDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMikiHisatomiDepartment of Oral and Maxillofacial Radiology, Okayama University HospitalShunsukeOkadaDepartment of Oral and Maxillofacial Radiology, Okayama University HospitalMamikoFujikuraDepartment of Oral and Maxillofacial Radiology, Okayama University HospitalYuriNambaDepartment of Oral and Maxillofacial Radiology, Okayama University HospitalSuzukaYoshidaDepartment of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSaoriYoshidaPreliminary Examination Room, Okayama University HospitalYoshinobuYanagiPreliminary Examination Room, Okayama University HospitalJunichiAsaumiDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe aim of this study is to assess the performance and utility of ChatGPT for the board qualification examination of the Japanese Society for Oral and Maxillofacial Radiology (JSOMR). We assessed ChatGPT responses to 149 multiple-choice questions written in Japanese for the board qualification examination of the JSOMR for the 3 years from 2020 to 2022. The questions were directly entered into ChatGPT-3.5 and ChatGPT-4 models manually one by one as a prompt. The accuracy rate was calculated and classified by year, type of multiple-choice question, and level of intellectual ability, and significant differences were noted. The accuracy rate of GPT-3.5 for the 3 years was 45.0% (51.0% for 2020, 34.0% for 2021, and 50.0% for 2022), while the accuracy rate of GPT-4 was 68.5% (73.5% for 2020, 62.0% for 2021, and 70.0% for 2022) for the board qualification examination of the JSOMR. GPT-4 had a significantly higher accuracy rate than GPT-3.5 in each year. On performance classified by the type of multiple-choice questions, GPT-4 performed significantly better than GPT-3.5. However, neither model performed well with questions that required interpretation or knowledge of Japanese law. The performance of GPT-4 was significantly superior to GPT-3.5 in the board qualification examination of the JSOMR, suggesting that the use of Chat GPT, especially ChatGPT-4, would be effective as a tool for learning and preparing for the examination.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-22532512025Clinical predictors of extubation failure in postoperative critically ill patients: a post-hoc analysis of a multicenter prospective observational study127ENJunHattoriFaculty of Medicine, Osaka UniversityAikoTanakaDepartment of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of MedicineJunkoKosakaDepartment of Anesthesiology and Resuscitology, Okayama University HospitalOsamuHiraoDepartment of Anesthesiology, Osaka General Medical CenterNanaFurushimaDepartment of Anesthesiology and Intensive Care Medicine, Kobe University HospitalYuichiMakiDepartment of Anesthesiology, Toho University Ohashi Medical CenterDaijiroKabataCenter for Mathematical and Data Science, Kobe UniversityAkinoriUchiyamaDepartment of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of MedicineMoritokiEgiDepartment of Anesthesia, Kyoto University HospitalHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University HospitalSatoshiMizobuchiDepartment of Anesthesiology and Intensive Care Medicine, Kobe University HospitalYoshifumiKotakeDepartment of Anesthesiology, Toho University Ohashi Medical CenterAyumiShintaniDepartment of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan UniversityYukikoKoyamaDepartment of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of MedicineTakeshiYoshidaDepartment of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of MedicineYujiFujinoDepartment of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of MedicineBackground Postoperative patients constitute majority of critically ill patients, although factors predicting extubation failure in this group of patients remain unidentified. Aiming to propose clinical predictors of reintubation in postoperative patients, we conducted a post-hoc analysis of a multicenter prospective observational study.<br>
Methods This study included postoperative critically ill patients who underwent mechanical ventilation for > 24 h and were extubated after a successful 30-min spontaneous breathing trial. The primary outcome was reintubation within 48 h after extubation, and clinical predictors for reintubation were investigated using logistic regression analyses.<br>
Results Among the 355 included patients, 10.7% required reintubation. Multivariable logistic regression identified that the number of endotracheal suctioning episodes during the 24 h before extubation and underlying respiratory disease or pneumonia occurrence were significantly associated with reintubation (adjusted odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05–1.18, p < 0.001; adjusted OR 2.58, 95%CI 1.30–5.13, p = 0.007). The probability of reintubation was increased significantly with the higher frequency of endotracheal suctioning, as indicated by restricted cubic splines. Subgroup analysis showed that these predictors were consistently associated with reintubation regardless of the use of noninvasive respiratory support after extubation.<br>
Conclusions Endotracheal suctioning frequency and respiratory complications were identified as independent predictors of reintubation. These readily obtainable predictors may aid in decision-making regarding the extubation of postoperative patients.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2363-90241112025Venous air embolism induced by burr hole drilling before dural incision in craniotomy: two case reports59ENYoheiMotoiDepartment of Anesthesiology and Resuscitology, Okayama University HospitalShujiOkaharaDepartment of Anesthesiology and Resuscitology, Okayama University HospitalMakikoTaniDepartment of Anesthesiology and Resuscitology, Okayama University HospitalNobushigeTsuboiDepartment of Neurosurgery, Okayama Red Cross HospitalHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University HospitalBackground: Venous air embolism (VAE) is a rare but potentially fatal complication in neurosurgery typically caused by injury to dura mater, especially venous sinuses, during craniotomy. We report two cases of VAE that occurred before dural incision.<br>
Case presentation: Both patients underwent craniotomy under general anesthesia in a head-up position. Hemodynamic and respiratory deterioration occurred during or immediately after burr hole drilling with abnormal vital signs and transesophageal echocardiography findings, raising suspicion for VAE. Immediate management, including surgical field protection and cardiopulmonary support, stabilized the patients’ conditions. The procedure was subsequently discontinued in case 1 and modified to limited resection in case 2. Postoperative computed tomography revealed intracranial venous air within the internal jugular vein, cavernous sinus, and diploic veins.<br>
Conclusion: These cases highlight that VAE can occur even before dural incision. Vigilant intraoperative monitoring and prompt intervention are essential for preventing potentially fatal outcomes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0913-86683922025T2 high-signal-intensity zone of the spinal cord dorsal horn in patients treated with spinal cord stimulation for herpes zoster-associated pain: a retrospective case–control study273281ENKyosukeArakawaDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasayukiNakagawaDepartment of Pain Management Clinic, NTT Medical Center TokyoYoichiroAbeDepartment of Pain Management Clinic, NTT Medical Center TokyoHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPurpose In patients with herpes zoster-associated pain (ZAP), magnetic resonance imaging (MRI) has revealed T2 high-signal intensity zones (MRI T2 HIZ) in the dorsal horn of the spinal cord, associated with postherpetic neuralgia (PHN). We retrospectively analyzed the relationship between PHN and MRI T2 HIZ in patients with refractory ZAP in the subacute phase who underwent temporary spinal cord stimulation therapy (tSCS).<br>
Methods This single-center, case–control study included patients who underwent tSCS for refractory ZAP between 2010 and 2018. MRIs were re-assessed for the presence of T2 HIZ in the dorsal horn of the spinal cord. Patients were divided into T2 HIZ( +) and T2 HIZ(−) groups. Patients with a numerical rating score (NRS) ≥ 3 at the last visit were defined as PHN. The NRS values and the incidence rate of PHN were compared between the two groups.<br>
Results Of the 67 cases extracted, 38 were included in the analysis: 22 in T2 HIZ( +) group and 16 in T2 HIZ(−) group. No significant differences were observed in background factors between the two groups. However, the T2 HIZ( +) group had a significantly higher NRS at the final visit (T2 HIZ( +):3.8 ± 2.1, T2 HIZ(−):1.4 ± 1.5; P < 0.05) and had significantly more patients with PHN than the T2 HIZ(−) group (T2 HIZ( +) vs. T2 HIZ(−), 15/22 (68%) vs. 3/16 (19%); odds ratio = 8.67; 95% confidence interval, 1.7–63.3).<br>
Conclusion T2HIZ is detected in more than half of refractory ZAP, and pain is more likely to remain after tSCS treatment in the T2HIZ( +) group.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-22532412024Efficacy of Pericapsular Nerve Group (PENG) block in preoperative rehabilitation (Prehabilitation) for patients with femoral neck fractures: study protocol for a randomized, placebo-controlled, double-blinded trial436ENZhuanJinDepartment of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineDaisukeSugiyamaDepartment of Anesthesiology, Kameda Medical CenterFumiyaHigoDepartment of Rehabilitation, Kameda Medical CenterTakahiroHirataDepartment of Rehabilitation, Kameda Medical CenterOsamuKobayashiDepartment of Anesthesiology, Kameda Medical CenterHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKenichiUedaDepartment of Anesthesiology, Kameda Medical CenterBackground Despite surgery intervention for femoral neck fractures is recommended within 48 h of admission, achieving timely surgery presents challenges for patients with severe comorbidities, or in resource-limited settings. Preoperative rehabilitation (prehabilitation) reduces bedridden time, enhances mobility, and improves postoperative outcomes for patients scheduled for hip arthroplasty due to femoral neck fractures. However, prehabilitation is hindered by insufficient pain control. The pericapsular nerve group (PENG) block provides effective analgesia while preserving motor function. We designed a study to assess the efficacy of PENG block in facilitating prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty.<br>
Methods This prospective randomized placebo-controlled double-blinded trial aims to enroll 100 patients with Garden 3 or 4 femoral neck fractures who are scheduled for hip arthroplasty. Participants will be randomly assigned to receive a PENG block with 0.375% ropivacaine (PENG group) or with normal saline (placebo group) before the initial prehabilitation session. The prehabilitation program comprises five items: Bed-sitting, Edge-sitting, Stand-up, Maintaining-standing, and Wheelchair-transfer, performed with the assistance of a single physical therapist. The primary outcome is the percentage of patients completing the entire prehabilitation program. Secondary outcomes during the initial prehabilitation session are the achievement of each program item and the Numerical Rating Scale (NRS) pain score. Other secondary outcomes include intraoperative bleeding amounts, thromboembolic events during postoperative day 0 to 7, postoperative 3-day cumulative Cumulated Ambulation Score (CAS), and discharge destination. The postoperative outcomes will be compared between subgroups of patients undergoing surgery within 48 h of admission and those undergoing surgery more than 48 h of admission.<br>
Discussion This is the first study aiming to assess the efficacy of PENG block in prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. PENG block could be beneficial, especially for patients facing delayed surgery, providing a potential treatment option during the waiting period.<br>
Trial registration Japan Registry of Clinical Trials, jRCT1031220294, registered on August 26, 2022.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2051-59601312025Rotenone targets midbrain astrocytes to produce glial dysfunction-mediated dopaminergic neurodegeneration234ENIkukoMiyazakiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNamiIsookaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoKikuokaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFuminoriImafukuDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoriMasaiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKanaTomimotoDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChiharuSogawaDepartment of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of TechnologyNorioSogawaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaKitamuraDepartment of Pharmacotherapy, School of Pharmacy, Shujitsu UniversityMasatoAsanumaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesExposure to pesticides, such as rotenone or paraquat, is an environmental factor that plays an important role in the pathogenesis of Parkinson's disease (PD). Rotenone induces PD-like pathology and is therefore used to develop parkinsonian animal models. Dopaminergic neurotoxicity caused by rotenone has been attributed to the inhibition of mitochondrial complex I, oxidative stress and neuroinflammation; however, the mechanisms underlying selective dopaminergic neurodegeneration by rotenone remain unclear. To resolve this, we focused on glial diversity and examined whether the brain region-specific glial response to rotenone could determine the vulnerability of dopaminergic neurons using primary cultured neurons, astrocytes and microglia from the midbrain and striatum of rat embryos and rotenone-injected PD model mice. Direct neuronal treatment with low-dose rotenone failed to damage dopaminergic neurons. Conversely, rotenone exposure in the presence of midbrain astrocyte and microglia or conditioned media from rotenone-treated midbrain glial cultures containing astrocytes and microglia produced dopaminergic neurotoxicity, but striatal glia did not. Surprisingly, conditioned media from rotenone-treated midbrain astrocytes or microglia monocultures did not affect neuronal survival. We also demonstrated that rotenone targeted midbrain astrocytes prior to microglia to induce dopaminergic neurotoxicity. Rotenone-treated astrocytes produced secreted protein acidic and rich in cysteine (SPARC) extracellularly, which induced microglial proliferation, increase in IL-1β and TNF-α, and NF-κB (p65) nuclear translocation in microglia, resulting in dopaminergic neurodegeneration. In addition, rotenone exposure caused the secretion of NFAT-related inflammatory cytokines and a reduction in the level of an antioxidant metallothionein (MT)-1 from midbrain glia. Furthermore, we observed microglial proliferation and a decrease in the number of MT-positive astrocytes in the substantia nigra, but not the striatum, of low-dose rotenone-injected PD model mice. Our data highlight that rotenone targets midbrain astrocytes, leading to SPARC secretion, which promotes the neurotoxic conversion of microglia and leads to glial dysfunction-mediated dopaminergic neurodegeneration.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2041-17231612025A node-localized efflux transporter for loading iron to developing tissues in rice9916ENJingCheInstitute of Plant Science and Resources, Okayama UniversityShengHuangInstitute of Plant Science and Resources, Okayama UniversityYutingQuState Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of SciencesYumaYoshiokaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChiyuriTomitaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakaakiMiyajiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityZhenyangLiuState Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of SciencesRenfangShenState Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of SciencesNaokiYamajiInstitute of Plant Science and Resources, Okayama UniversityJian FengMaInstitute of Plant Science and Resources, Okayama UniversityIron (Fe) is an essential micronutrient for plant growth and development. It plays crucial roles in various organs and tissues of plants, but the molecular mechanisms governing its distribution to the above-ground parts after root uptake remain unclear. In this study, we identify OsIET1 (Oryza sativa Iron Efflux Transporter 1), a rice gene highly expressed in the nodes. OsIET1 encodes a plasma membrane-localized protein, which shows efflux transport activity for ferrous iron. It is predominantly expressed in the xylem regions of diffuse vascular bundles, and its expression is upregulated under high Fe conditions. Disruption of OsIET1 impairs Fe allocation, reducing Fe transport to developing tissues (young leaves and grains), while increasing accumulation in nodes and older leaves. This misdistribution causes chlorosis in young leaves and decreases grain yield, especially under Fe-deficient conditions. Furthermore, we detect excessive Fe deposition around the xylem of diffuse vascular bundles in the nodes. Given the pivotal role of nodes in mineral distribution, our results indicate that OsIET1 mediates inter-vascular Fe transfer by facilitating Fe loading into the xylem of diffuse vascular bundles. This process ensures preferential Fe delivery to developing tissues, thereby promoting optimal plant growth and productivity.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy38590ENChiakiYagiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShinjiKurodaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShunyaHanzawaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineDaisukeKadowakiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYusukeYoshidaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasakiSakamotoDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYukiHamadaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineRyomaSugimotoDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTomokoOhtaniDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKentoKumonDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasashiHashimotoDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNobuhikoKanayaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSatoruKikuchiDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShunsukeKagawaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHiroshiTazawaDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYasuoUrataOncolys BioPharma, Inc.ToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineOncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0007-09202025Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1/2 pathway promote chemoresistance in pancreatic cancerENShoheiNogiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsukiTaniguchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohikoYagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshiyasuKonoDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and chemoresistance poses a significant challenge in its treatment. Neutrophil extracellular traps (NETs) have emerged as key players in the tumour microenvironment, but their role in chemoresistance remains unclear.<br>
Methods: We investigated the involvement of NETs in PDAC chemoresistance using patient tumour samples, in vitro assays with gemcitabine (GEM)-treated PDAC cells, and in vivo mouse models. We evaluated cytokine production, NET formation and tumour response to GEM, with or without the CXCR1/2 inhibitor navarixin.<br>
Results: NETs are significantly accumulated in the tumours of PDAC patients exhibiting poor response to chemotherapy. GEM-treated PDAC cells secrete pro-inflammatory cytokines such as interleukin-8 (IL-8). IL-8 promote the formation of chemotherapy-induced NETs (chemoNETosis) through activation of CXCR 1/2 on neutrophils. Importantly, treatment with navarixin significantly suppressed chemoNETosis, restored sensitivity to GEM, and significantly reduced tumour growth in vivo.<br>
Conclusions: Our findings reveal that NETs contribute to chemoresistance in PDAC and that IL-8–mediated chemoNETosis plays a pivotal role in this process. Inhibition of CXCR1/2-mediated NET formation enhances the efficacy of GEM. This approach may represent a promising therapeutic strategy for overcoming chemoresistance in PDAC. These results support further clinical investigation of anti-NETs therapies.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025iTRAQ-based quantitative proteomics reveals reduced expression of KRT19, KRT7, and PTGDS in cutaneous specimens after kidney transplantation33014ENIchiroTsuboiDepartment of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYosukeMitsuiDepartment of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKasumiYoshinagaDepartment of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTomoakiYamanoiDepartment of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakanoriSekitoDepartment of Inflammation and Immunity, Lerner Research Institute Cleveland ClinicYukiMaruyamaDepartment of Inflammation and Immunity, Lerner Research Institute Cleveland ClinicTakuyaSadahiraDepartment of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShingoNishimuraDepartment of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKensukeBekkuDepartment of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMotooArakiDepartment of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineClinical improvement in pigmentation is frequently observed after kidney transplantation. However, the underlying molecular and histological mechanisms remain unclear. We conducted a study to quantify the skin color change using a handheld reflected light colorimeter and to investigate protein expression changes in the skin before and after kidney transplantation. Paired skin biopsies were obtained from three patients who underwent kidney transplantation before and one month after transplantation. Protein expression was analyzed using iTRAQ-based quantitative proteomics. Differentially expressed proteins were identified and visualized using hierarchical clustering and volcano plots. Histopathological evaluation included hematoxylin and eosin (H&E), Masson’s trichrome, and immunohistochemical (IHC) staining for keratin (KRT) 7, KRT19, and MelanA. Skin pigmentation of the arms, ankles, and abdomen had significant L-value improvement after kidney transplantation. Proteomic profiling identified 2148 proteins, with six proteins showing significant differential expression after transplantation. Among them, KRT7, KRT19, and prostaglandin D2 synthase (PTGDS) were significantly downregulated, potentially reflecting reduced epithelial stress and systemic inflammation. H&E and Masson’s trichrome staining revealed a post-transplantation reduction in dermal pigmentation and collagen content. IHC showed decreased KRT7, KRT19, and MelanA expression after transplantation. Our results suggest that targeting KRT or prostaglandin pathways may offer new treatments for ESRD-related skin symptoms.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1618-12472025Admission prognostic nutritional index predicts prolonged hospitalization in severe odontogenic deep neck infectionsENEijiIwataDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyoichiObataDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShogoKikutaDental and Oral Medical Center, Kurume University School of MedicineNaokiKanekoSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu UniversityKotaroSatoDepartment of Oral and Maxillofacial Surgery, Nagoya University Graduate School of MedicineNorioKitagawaDepartment of Oral and Maxillofacial Anatomy, Graduate School of Medical and Dental Sciences, Institute of Science TokyoYoheiTakeshitaDepartment of Oral and Maxillofacial Radiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKatsuhisaMatsuoDental and Oral Medical Center, Kurume University School of MedicineJunseiSameshimaSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu UniversityAkiraTachibanaDepartment of Oral and Maxillofacial Surgery, Kakogawa Central City HospitalShintaroKawanoSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu UniversityJingoKusukawaDental and Oral Medical Center, Kurume University School of MedicineMasayaAkashiDepartment of Oral and Maxillofacial Surgery, Kobe University Graduate School of MedicineJoeIwanagaDental and Oral Medical Center, Kurume University School of MedicineSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityObjectives Severe odontogenic deep neck infections (DNIs) can be life threatening. This study investigated the nutritional status of affected patients and evaluated the usefulness of the Prognostic Nutritional Index (PNI) at admission in helping maxillofacial surgeons identify, at presentation, those likely to require extended hospitalization.<br>
Methods A total of 112 patients treated for odontogenic deep neck abscesses and necrotizing soft tissue infections at five hospitals in Japan. Patients were included. Patients were categorized by length of hospitalization duration and factors associated with prolonged hospitalization were analyzed using propensity score matching to minimize bias. Spearman’s rank correlation analysis was also performed to assess the relationship between PNI and hospitalization duration.<br>
Results Fifty patients (44.6%) required hospitalization for more than 14 days. Multivariate analysis identified PNI ≤ 41.2 (odds ratio [OR] = 2.79) and the presence of abscesses in multiple deep neck spaces (OR = 2.76) as significant predictors of prolonged hospitalization. Propensity score analysis confirmed the significant association between PNI and length of hospitalization duration (P = 0.048). In addition, Spearman’s rank correlation coefficient was r = − 0.471 (P < 0.001), indicating a moderate negative correlation.<br>
Conclusion The admission PNI may serve as a useful adjunctive indicator for predicting prolonged hospitalization in patients with severe odontogenic DNIs, as it reflects both nutritional status and systemic inflammation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1939-59812025Effect of Repeated Gravity Casting on the Microstructure and Mechanical Properties of 6061 Aluminum AlloyENMitsuhiroOkayasuDepartment of Mechanical Systems and Engineering, Okayama UniversityShoueiMakinoDepartment of Mechanical Systems and Engineering, Okayama UniversityShotaNakagawaResearch & Development Center, Marketing & Technology Division, UACJ CorporationShuheiTakeuchiDepartment of Mechanical Systems and Engineering, Okayama UniversityYoshifumiShinzatoResearch & Development Center, Marketing & Technology Division, UACJ CorporationTadashiMinodaResearch & Development Center, Marketing & Technology Division, UACJ CorporationNaotakaOhtsukaResearch & Development Center, Marketing & Technology Division, UACJ CorporationThis study systematically investigates the effects of repeated gravity casting on the microstructure and mechanical properties of 6061 aluminum alloy. With an increasing number of casting cycles from one to ten, grain coarsening and a decrease in dislocation density were observed, mainly due to the significant depletion of magnesium from 1.03 to 0.01% and titanium from 0.009 to 0.005%. These microstructural changes led to a decrease in solid-solution strengthening and grain-boundary strengthening, resulting in a 30% reduction in tensile strength, while ductility increased by about three times. Moreover, work hardening decreased with increasing the casting cycle, which can be attributed not only to the microstructural changes but also to the increase in stacking fault energy (SFE) associated with compositional evolution. From the transmission electron microscopy (TEM) observations, in the 1-cycle sample, Mg2Si precipitates were finely dispersed and a high amount of Mg element in the matrix, resulting in significant dislocation accumulation, whereas the 10-cycle sample exhibited weaker dislocation tangling. These microstructural evolutions provide insight into the degradation of mechanical performance in aluminum alloys subjected to multiple casting processes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2510-15602025Enhanced electric power generation in PZT ceramics via stress controlENMitsuhiroOkayasuDepartment of Mechanical Systems and Engineering, Okayama UniversityItsukiShimazuDepartment of Mechanical Systems and Engineering, Okayama UniversityThis study aimed to enhance the electric power generation of lead zirconate titanate piezoelectric (PZT) ceramics by optimizing stress distribution. Specifically, it focused on applying high stress over a broad area of the PZT ceramic to induce shape deformation in the PZT plate. Pre-straining the PZT plate into an arch shape improved voltage generation, reaching its peak at a maximum deflection of 0.04 mm due to the expanded and intensified stress distribution. However, exceeding this deflection threshold led to a decline in voltage output due to material degradation, including crack formation and 90° domain switching. Finite element analysis confirmed that the increased stress distribution in the pre-strained PZT plate contributed to higher voltage output. Additionally, electron backscatter diffraction analysis revealed that at higher pre-strains (deflection of 0.08 mm), 90°domain switching occurred, resulting in increased internal strain and potential crack formation. Experimental investigations using bulk PZT rods further demonstrated that moderate pre-straining effectively enhanced voltage output.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1939-59812025Upgrading Recycle Technology for Iron Removal in ADC12 Alloy Using Gravity and Magnetic ForceENM.OkayasuDepartment of Mechanical Systems and Engineering, Okayama UniversityS.TakeuchiDepartment of Mechanical Systems and Engineering, Okayama UniversityM.SyahidDepartment of Mechanical Engineering, Hasanuddin UniversityT.IkedaDepartment of Mechanical Systems and Engineering, Okayama UniversityAs there is a technical issue to remove iron elements during aluminum recycling process, an attempt was made to evaluate the effectiveness of magnetic and gravitational separation methods for removing iron from Al-Si-Cu alloy (ADC12). A rare-earth samarium–cobalt (SmCo) magnet was employed during the solidification process to attract Fe-rich eutectic structures. The microstructural analysis revealed that block-like Fe-Cr-Si-based phases formed preferentially near the magnet and at the bottom of the crucible, suggesting that magnetic and gravity attraction contributed to the localized segregation of these phases. However, other Fe-based phases, including Fe-Si-based ones, are not strongly affected by magnet. Additionally, prolonged heating in the solid–liquid coexistence (SLC) region at 577 °C for 10 h led to the settling of a largely grown Fe-Cr-Si-rich crystal at the bottom of the crucible due to gravity. Other structures, such as Si-rich eutectic phases, were not influenced by gravity, which may be caused by the low density of Si compared to Fe one. From this approach, combining magnetic attraction and gravitational settling is a promising method to promote the removal of iron impurities from aluminum alloys.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0361-52355472025Electric Power Generation of PZT Piezoelectric Ceramics Using Both Direct and Inverse Piezoelectric Effects51435150ENMitsuhiroOkayasuDepartment of Mechanical Systems and Engineering, Okayama UniversityItsukiShimazuDepartment of Mechanical Systems and Engineering, Okayama UniversityThe power generation characteristics of lead zirconate titanate (PZT) piezoelectric ceramics (E-PZT) were experimentally investigated using a specialized PZT system which utilizes both the direct and inverse piezoelectric effects inherent to PZT materials. Specifically, electric voltage was generated from the vibration of E-PZT through the inverse piezoelectric effect, induced by mechanical energy transferred from the vibration of a PZT piezoelectric ceramic plate, such as a buzzer (B-PZT). In this system, an insulating material was placed between the B-PZT and E-PZT plates to address the electrical conductivity of the PZT ceramic. Various insulating materials with different thicknesses and different hardness were prepared. Additionally, the PZT systems were mounted in several distinct configurations to evaluate their power generation performance: a fully fixed around the PZT plate and a free-hanging setup. The influence of insulation materials and mounting conditions on electrical output was analyzed at various loading conditions, e.g., loading value and frequency. The results demonstrated that the generated electric voltage decreased with increasing insulation thickness and hardness, suggesting that thinner and softer insulating materials enhance output voltage. Conversely, when the PZT system was securely fixed around the PZT plate with an appropriate fixture, a higher and more stable electric voltage was generated. The voltage generated also varied by the loading condition, which is related to the strain value of the E-PZT plate, demonstrating a linear relationship between the strain and the output voltage. Notably, the strain was significantly influenced by resonant frequencies, which played a crucial role in achieving higher voltage outputs. Based on these experimental results, two power generation systems have been proposed.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841792025The Intranasal Administration of Semaphorin 3A Inhibitor in a Mouse Model of Olfactory Disordere92587ENAyaMuraiOtolaryngology - Head and Neck Surgery, Okayama University HospitalMinoriNodaOtolaryngology - Head and Neck Surgery, Okayama University HospitalAikoShimizuOtolaryngology - Head and Neck Surgery, Okayama University HospitalJunkoTakaharaDivision of Technical Support for Medical Science, Department of Comprehensive Technical Solutions, Okayama UniversitySeiichiroMakiharaOtolaryngology - Head and Neck Surgery, Okayama University HospitalMizuoAndoOtolaryngology - Head and Neck Surgery, Okayama UniversityThis study investigated the effects of intranasal administration of a semaphorin 3A inhibitor (Sema3A-I) in a mouse model of olfactory disorder, where olfactory sensory neuron (OSN) axons had been severely damaged. We performed axotomy (transection of OSN axons) of the OSNs in mice and administered Sema3A‑I intranasally to seven mice and saline to another seven mice. Following treatment, we assessed the thickness of the olfactory epithelium and the regeneration ratio of OSN axons. Intranasal administration of Sema3A-I did not significantly promote OSN regeneration, axonal outgrowth, or improve axonal projection compared to saline administration. Although Sema3A-I administration showed some promotion of axonal outgrowth, the difference was not statistically significant. Continuous subcutaneous administration of Sema3A-I in rats after axotomy promotes OSN regeneration and axonal outgrowth. Given that intranasal administration is minimally invasive, we believe that it may still be a feasible route when combined with additional treatment strategies. Further investigation into administration methods and therapeutic combinations is warranted.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841782025A Higher Liver Fibrosis-4 Index Is Associated With More Severe Hearing Loss in Idiopathic Sudden Sensorineural Hearing Losse89864ENYukihideMaedaDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSoshiTakaoDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyotaroOmichiDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMizuoAndoDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground<br>
Liver fibrosis is an important medical issue increasing over time in developed countries.<br>
Aims/objectives<br>
This study aimed to investigate whether liver fibrosis, as indicated by routine blood test parameters, influences the risk and severity of idiopathic sudden sensorineural hearing loss (ISSNHL).<br>
Material and methods<br>
Sixty-six patients with ISSNHL and 198 patients with benign parotid gland tumors (BPTs) (controls) were enrolled. Indices for liver fibrosis (Liver Fibrosis-4 index (FIB-4 index) and aspartate aminotransferase-to-platelet ratio index (APRI)) were calculated from the blood laboratory data. The pure tone average (PTA) was calculated as the mean of hearing levels at the six frequencies at the onset of ISSNHL. Severe hearing loss was defined as PTA≥60 decibels Hearing Level (dB HL).<br>
Results<br>
In risk evaluation, the FIB-4 index did not differ significantly between ISSNHL patients and controls. Regarding the severity of ISSNHL, the FIB-4 index was significantly higher in ISSNHL patients with severe hearing loss than in those with PTA<60 dB HL (P<0.05) on univariate comparison. After adjusting for age, sex, and indices of inflammation, both the FIB-4 index and APRI showed a significant association with severe hearing loss (odds ratio (OR): 5.9, 95% confidence interval (CI): 1.3-25.7, and OR: 2.2, 95% CI: 1.1-4.7).<br>
Conclusions and significance<br>
Higher liver fibrosis indices (FIB-4 index and APRI), derived from routine blood laboratory data, are associated with a more severe phenotype of ISSNHL.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025The significance of adding posterior decompression to spine stabilization in metastatic spinal surgery: a multicenter prospective study27684ENHiroyukiTominagaDepartment of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityIchiroKawamuraDepartment of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityHirofumiShimadaDepartment of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityHiromiSasakiDepartment of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityNoboruTaniguchiDepartment of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityYukiShirataniDepartment of Orthopaedic Surgery, Graduate School of Medicine, Chiba UniversityAkinobuSuzukiDepartment of Orthopaedic Surgery, Osaka Metropolitan UniversityHidetomiTeraiDepartment of Orthopaedic Surgery, Osaka Metropolitan UniversityTakakiShimizuDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa UniversityKenichiroKakutaniDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineYutaroKandaDepartment of Orthopaedic Surgery, Kobe University Graduate School of MedicineMasayukiIshiharaDepartment of Orthopaedic Surgery, Kansai Medical University HospitalMasaakiPakuDepartment of Orthopaedic Surgery, Kansai Medical University HospitalYoheiTakahashiDepartment of Orthopaedic Surgery, Keio UniversityToruFunayamaDepartment of Orthopaedic Surgery, Institute of Medicine, University of TsukubaKouseiMiuraDepartment of Orthopaedic Surgery, Institute of Medicine, University of TsukubaEikiShirasawaDepartment of Orthopaedic Surgery, Kitasato University School of MedicineHirokazuInoueRehabilitation Center, Jichi Medical University HospitalAtsushiKimuraDepartment of Orthopaedics, Jichi Medical UniversityTakuyaIimuraDepartment of Orthopaedic Surgery, Dokkyo Medical UniversityHiroshiMoridairaDepartment of Orthopaedic Surgery, Dokkyo Medical UniversityHideakiNakajimaDepartment of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of FukuiShujiWatanabeDepartment of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of FukuiKojiAkedaDepartment of Orthopaedic Surgery, Mie University Graduate School of MedicineNorihikoTakegamiDepartment of Orthopaedic Surgery, Mie University Graduate School of MedicineKazuoNakanishiDepartment of Orthopaedic Surgery, Kawasaki Medical SchoolHirokatsuSawadaDepartment of Orthopaedic Surgery, Nihon University School of MedicineKojiMatsumotoDepartment of Orthopaedic Surgery, Nihon University School of MedicineMasahiroFunabaDepartment of Orthopaedics Surgery, Yamaguchi University Graduate school of MedicineHidenoriSuzukiDepartment of Orthopaedics Surgery, Yamaguchi University Graduate school of MedicineHarukiFunaoDepartment of Orthopaedic Surgery, International University of Health and Welfare Narita HospitalTsutomuOshigiriDepartment of Orthopaedic Surgery, Sapporo Medical University School of MedicineTakashiHiraiDepartment of Orthopedic Surgery, Institute of Science TokyoBungoOtsukiDepartment of Orthopaedic Surgery, Kyoto University HospitalKazuKobayakawaDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu UniversityKojiUotaniDepartment of Orthopaedic Surgery, Okayama University HospitalHiroakiManabeDepartment of Orthopedics, Tokushima UniversityShinjiTanishimaDivision of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori UniversityKoHashimotoDepartment of Orthopaedic Surgery, Tohoku University Graduate School of MedicineChizuoIwaiDepartment of Orthopaedic Surgery, Gifu University HospitalDaisukeYamabeDepartment of Orthopaedic Surgery, Iwate Medical UniversityAkihikoHiyamaDepartment of Orthopaedic Surgery, Tokai University School of MedicineShojiSekiDepartment of Orthopaedic Surgery, University of ToyamaYutaGotoDepartment of Orthopaedic Surgery, Nagoya City UniversityMasashiMiyazakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityKazuyukiWatanabeDepartment of Orthopaedic Surgery, Fukushima Medical University School of MedicineToshioNakamaeDepartment of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityTakashiKaitoDepartment of Orthopedic Surgery, Osaka University Graduate School of MedicineHiroakiNakashimaDepartment of Orthopaedic Surgery, Nagoya University Graduate School of MedicineNarihitoNagoshiDepartment of Orthopaedic Surgery, Keio UniversitySatoshiKatoDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa UniversityShiroImagamaDepartment of Orthopaedic Surgery, Nagoya University Graduate School of MedicineKotaWatanabeDepartment of Orthopaedic Surgery, Keio UniversityGenInoueDepartment of Orthopaedic Surgery, Kitasato University School of MedicineTakeoFuruyaDepartment of Orthopaedic Surgery, Graduate School of Medicine, Chiba UniversityThe usefulness of spine stabilization for treating metastatic spinal tumors with tumor-induced instability has been reported. However, no reports have prospectively evaluated the effectiveness of adding posterior decompression to stabilization surgery for improving symptoms. This multicenter prospective study aimed to determine whether adding posterior decompression to spine stabilization surgery for metastatic spinal tumors affects postoperative outcomes and complications. A total of 263 patients who underwent spine stabilization with (n = 189) or without (n = 74) decompression were analyzed. Patient demographics, the Spinal Instability Neoplastic Score (SINS), and the Epidural Spinal Cord Compression (ESCC) score were recorded. The outcomes were assessed preoperatively and at 1 and 6 months postoperatively in terms of neurological status, the Barthel Index, the EQ-5D-5 L, and the visual analog scale (VAS). Decompression was primarily performed in patients with severe neurological deficits and high-grade ESCC. Both groups showed postoperative improvement. Propensity score matching was applied to adjust for baseline differences. After matching, there were no significant differences in functional improvement between the decompression and nondecompression groups, and the complication rates were comparable. In matched patients presenting primarily with spinal instability and pain, the addition of decompression did not appear to confer a significant functional benefit within 6 months postoperatively.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841792025Incidence and Factors Influencing Locomotive Syndrome in Cancer Patients Living in the Communitye91856ENYoshiteruAkezakiDivision of Physical Therapy, Kochi Professional University of RehabilitationEijiNakataDepartment of Orthopaedic Surgery, Okayama University HospitalMasatoKikuuchiDepartment of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer CenterYoshimiKatayamaDepartment of Rehabilitation Medicine, Okayama University HospitalShinsukeSugiharaDepartment of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer CenterBackground Investigating locomotive syndrome (LS) of cancer survivors in the community will help clarify the importance of rehabilitation for cancer survivors in the community and provide a basis for exploring effective interventions. The primary purpose of this study was to conduct a comparison of LS, fatigue, psychological problems, and physical activity in cancer survivors and those without cancer in the community. The secondary purpose was to analyze factors influencing LS in cancer patients.<br>
Methods The study involved 59 cancer patients undergoing chemotherapy at home and 59 people without cancer. The cancer patients were those undergoing chemotherapy as outpatients and constituted the cancer group. The non-cancer people were living in the community and constituted the non-cancer group.<br>
Cancer and non-cancer groups were surveyed and measured for LS, fatigue, psychological problems, and physical activity. The cancer group was also surveyed for the duration of chemotherapy treatment and the presence or absence of bone metastases.<br>
Results The cancer group was significantly more likely than the non-cancer group to have LS stage 2, to have fatigue, and to have psychological problems. Fatigue and psychological problems were significantly associated with LS stage 2.<br>
Conclusions Cancer patients in the community need to be assessed regularly by healthcare providers and interventions should be made according to their condition.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1439-01082025Coupling effects of biochar and sediment microbial fuel cells on CH4 and CO2 emissions from straw-amended paddy soilENAdhena TesfauBekeleGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMorihiroMaedaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNozomiNakaharaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityAyumiHashiguchiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroakiSomuraGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySatoshiAkaoFaculty of Science and Engineering, Doshisha UniversityChiyuNakanoDepartment of Comprehensive Technical Solutions, Okayama UniversityYutaNishinaResearch Institute for Interdisciplinary Science, Okayama UniversityPurpose The independent incorporation of biochar and sediment microbial fuel cells (SMFCs) into paddy soil has been shown to reduce methane (CH4) emissions. However, the application of rice straw into paddy soil enhances the availability of labile carbon that stimulates methanogen growth, counteracting the mitigation effects of both methods. This study, therefore, aimed to investigate the effect of coupling biochar and SMFC on CH4 and CO2 emissions from straw-amended paddy soil.<br>
Materials and methods Single chamber SMFC setups constructed using acrylic columns (height, 25 cm; inner diameter, 9 cm) with six treatments were established using soil amended with 0% (0BC), 1% (1BC), and 2% (2BC) biochar: with and without SMFC conditions. Stainless steel mesh (15 × 3 cm) and graphite felt (6 × 5 cm) were used as anode and cathode materials, respectively.<br>
Results Cumulative emission of CH4 in the 0BC treatment with SMFC was 39% less than in that without SMFC. Biochar addition and SMFC operation together further reduced CH4 emission by 57% and 60% in 1BC and 2BC treatments, respectively, compared to that in the 0BC treatment without SMFC operation. The relative abundance of microbial communities indicated methane-oxidizing bacteria were enriched in the presence of biochar and hydrogenotrophic Methanoregula were suppressed by SMFC operation. This suggested that SMFC mainly inhibited CH4 production by outcompeting hydrogenotrophic archaea.<br>
Conclusion The use of biochar made from leftover rice straw has an interactive effect on SMFC operation and both methods can be used to reduce CH4 emission from straw-amended paddy soil.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841772025Prevalence of Locomotive Syndrome in Perioperative Patients With Localized Cancere88699ENYoshimiKatayamaDepartment of Rehabilitation Medicine, Okayama University HospitalEijiNakataDepartment of Orthopaedic Surgery, Okayama University HospitalTakutoItanoDepartment of Orthopaedic Surgery, Okayama University HospitalYoshiteruAkezakiDivision of Physical Therapy, Kochi Professional University of RehabilitationMasanoriHamadaDepartment of Rehabilitation Medicine, Okayama University HospitalToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University HospitalIntroduction<br>
Many patients with cancer experience reduced activities of daily living due to muscle weakness and fatigue caused by underlying symptoms and treatment side effects. However, the incidence of locomotive syndrome, which may reduce mobility due to motor dysfunction in patients with cancer, has not been sufficiently explored. Therefore, we aimed to investigate the incidence of locomotive syndrome and identify its risk factors in perioperative patients with cancer.<br>
<br>
Methods<br>
We included 636 perioperative patients with localized cancer who were treated between 2020 and 2023. The severity of locomotive syndrome was classified into stages 1, 2, and 3.<br>
<br>
Results<br>
The overall locomotive syndrome rate was 88.1%, with distribution across stages: stage 1 (56.8%), stage 2 (17.5%), and stage 3 (13.8%). Among men, the overall incidence was 86.5%, with stage 1 (60.3%), stage 2 (15.5%), and stage 3 (10.7%). Among women, the overall incidence was 90.6%, with stage 1 (50.6%), stage 2 (20.9%), and stage 3 (19.1%). Half of patients in their 20s and two-thirds in their 30s had locomotive syndrome. The rates were 58.6%, 80.4%, 81.8%, 93.2%, and 97.8% in the 40s, 50s, 60s, 70s, and 80s age groups, respectively. Individuals in their 40s had significantly lower rates than those in older groups. Age, grip strength, and percent vital capacity were identified as risk factors.<br>
<br>
Conclusion<br>
A high prevalence of locomotive syndrome was observed among patients with localized cancer. Age, reduced grip strength, and lower respiratory capacity were identified as associated factors. While the findings suggest possible implications for postoperative recovery, further validation through longitudinal studies is required.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417102025Histopathological Study of Regenerative Endodontic Therapy on an Immature Mandibular Second Premolar With Pulp Necrosis: A Case Reporte95647ENHidefumiSakoDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalKazuhiroOmoriDepartment of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiShinoda-ItoDepartment of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKiyofumiTakabatakeDepartment of Oral Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShogoTakashibaDepartment of Pathophysiology - Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRegenerative endodontic therapy (revascularization) for immature permanent teeth with pulp necrosis and/or apical periodontitis is an effective treatment to promote root maturation. Previous histological studies have reported the formation of cementoid or osteoid tissue and periodontal ligament-like tissue within the root canals. This case report presents the histopathological findings of a human immature permanent tooth with pulp necrosis following revascularization.<br>
<br>
A 11-year-old male patient presented with tenderness on biting and the formation of a sinus tract in the mandibular right second premolar (tooth #29), diagnosed as pulp necrosis with symptomatic apical periodontitis. Revascularization was performed using calcium hydroxide as an intracanal medicament, with reference to the American Association of Endodontists (AAE) 2018 Position Paper on Regenerative Endodontics. At the 12-month follow-up, radiographs showed thickening of the canal walls, apical narrowing, root elongation, and recovery of pulp sensibility. The tooth was later extracted for orthodontic reasons at 42 months and processed for histological examination.<br>
<br>
Histological evaluation revealed cementum-like hard tissue continuous with the existing dentin in the apical region, suggesting apical closure. In contrast, the coronal portion showed less mature cementum-like tissue accompanied by loose connective tissue and neovascularization. These findings indicate that revascularization with calcium hydroxide can induce the formation of cementum-like and dentin-like tissues with vascular regeneration in immature permanent teeth with pulp necrosis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841782025Subacute Progression of Gait Disturbance and Consciousness Impairment Due to Communicating Hydrocephalus Associated With Vestibular Schwannomae89880ENSatokaYanoDepartment of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of MedicineAkatsukiKubotaDepartment of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of MedicineMizuhoKawaiDepartment of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of MedicineDaikiYashitaDepartment of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of MedicineHiroyukiIshiuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesWataruSatakeDepartment of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of MedicineKaoruYamadaDepartment of Neuropathology, The University of Tokyo Graduate School of Medicine and Faculty of MedicineYukiShinyaDepartment of Neurosurgery, The University of Tokyo Graduate School of Medicine and Faculty of MedicineSatoruMiyawakiDepartment of Neurosurgery, The University of Tokyo Graduate School of Medicine and Faculty of MedicineTakeshiIwatsuboDepartment of Neuropathology, The University of Tokyo Graduate School of Medicine and Faculty of MedicineTatsushiTodaDepartment of Neurology, The University of Tokyo Graduate School of Medicine and Faculty of MedicinePatients with vestibular schwannomas (VSs) present with vestibulocochlear nerve dysfunction such as vertigo and tinnitus. VSs occasionally develop communicating hydrocephalus as a complication, which is typically characterized by an insidious progression of symptoms. We report a case of an 84-year-old female patient with a VS who developed gait disturbance and consciousness impairment over a three-week period, ultimately resulting in an inability to walk and communicate. A thorough evaluation ruled out encephalitis and other differential diagnoses. Imaging studies demonstrated findings consistent with communicating hydrocephalus, and a tap test temporarily improved her consciousness disturbances. The patient underwent ventriculoperitoneal shunting and stereotactic radiosurgery (SRS), after which both consciousness and gait disturbances dramatically improved 10 days postoperatively. The subacute development of symptoms due to normal pressure hydrocephalus associated with VSs is rare. Furthermore, to the best of our knowledge, this is the first reported case of severe gait impairment and disturbance of consciousness progressing within a short period. This case highlights the importance of considering communicating hydrocephalus associated with VSs as a differential diagnosis, even in cases of subacute consciousness disturbance. We also discuss the pathophysiology of hydrocephalus in relation to cerebrospinal fluid (CSF) clearance into the extracranial space. No potential conflict of interest relevant to this article was reported.Springer Nature SingaporeActa Medica Okayama1865-09292025Evaluation of a Startup Program Identification for Efficient and Accurate IoT Security Investigations417431ENYutaShimamotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityJiratchayaPhinyodomSchool of Engineering, Okayama UniversityRyotaYoshimotoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityHiroyukiUekawaNTT Social Informatics LaboratoriesMitsuakiAkiyamaNTT Social Informatics LaboratoriesToshihiroYamauchiFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityNot all file in firmware are executed while using Internet of Things (IoT) devices and hundreds to approximately a thousand executable and linkable format files exist in one firmware. Therefore, security investigations without prioritization may lead to investigate programs that are not executed while using IoT devices first. This has resulted in inefficient security investigations. To perform efficient security investigations, we proposed a method that can identify programs executed during the startup process. However, only two firmware were used for the evaluation which can only evaluate one of the two startup sequences in the OpenWrt-based firmware. In addition, security investigations to validate whether the proposed method addresses the problem of inefficient security investigations were limited to OpenWrt-based firmware. In this study, we use more firmware data for evaluation and validation. We use nine firmware not used in previous studies including startup methods that have not previously been used for evaluation. In addition, we increase the number of firmware used for validation to 225. The evaluation results demonstrate that the proposed method can identify with only few false positives. The validation demonstrates that efficiency can be improved and prioritizing investigations by considering the proposed method result is worthwhile.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1434-391614512025Component placement angles in total knee arthroplasty affect mid- to long-term clinical results: an average 8-year follow-up study457ENKokiKawadaDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeYokoyamaDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomonoriTetsunagaDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazukiYamadaDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiOkazakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshikiKoharaDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshifumiOzakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction Few studies have examined how the component placement angles in total knee arthroplasty (TKA) affect mid- to long-term clinical outcomes. This study investigated the influence of coronal and sagittal plane component placement angles on mid- to long-term outcomes in mechanical alignment TKA.<br>
Materials and Methods Forty-eight knees undergoing TKA using the FINE Total Knee System were evaluated for range of motion (ROM) preoperatively. Both ROM and clinical scores were evaluated at 3 and 5 years postoperatively and at the final follow-up (average 8-year). The valgus (alpha) and flexion (gamma) angles of the femoral component, and the varus (beta) and posterior tilt (sigma) angles of the tibial component were evaluated. Correlations between radiographic assessments, knee ROM, and clinical scores were assessed using Spearman's correlation coefficient.<br>
Results The alpha angle was negatively correlated with the knee flexion angle (r = − 0.323, p = 0.025) and ROM (r = − 0.352, p = 0.014), and the sigma angle was negatively correlated with the Knee Injury and Osteoarthritis Outcome Score (KOOS)-Symptoms at 3 years postoperatively (r = − 0.304, p = 0.036). The alpha angle was negatively correlated with the knee flexion angle (r = − 0.357, p = 0.013), ROM (r = − 0.337, p = 0.019), and KOOS-Sports and Recreation function (r = − 0.349, p = 0.015), and positively correlated with the Visual Analog Scare pain score (r = 0.307, p = 0.034) at the final follow-up. The beta angle was positively correlated with KOOS-Pain (r = 0.303, p = 0.036) and KOOS-Symptoms (r = 0.397, p = 0.005) at the final follow-up.<br>
Conclusions Valgus placement of the femoral component and varus placement of the tibial component in the FINE Total Knee System negatively impacted clinical scores at an average 8-year follow-up.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0916-70052025Refinement of interval approximations for fully commutative quiversENYasuakiHiraokaKyoto UniversityKenNakashimaShimane UniversityIppeiObayashiOkayama UniversityChenguangXuKyoto UniversityA central challenge in the theory of multiparameter persistence modules lies in defining effective descriptors for representations of infinite or wild type. In this work, we propose a novel framework for analyzing interval approximations of fully commutative quivers, which offers a tunable trade-off between approximation resolution and computational complexity. Our approach is evaluated on commutative ladder modules of both finite and infinite type. For finite-type cases, we establish an efficient method for computing indecomposable decompositions using solely one-parameter persistent homology. For infinite-type cases, we introduce a new invariant that captures persistence in the second parameter by connecting standard persistence diagrams through interval approximations. Furthermore, we present several models for constructing commutative ladder filtrations, providing new insights into the behavior of random filtrations and demonstrating the utility of our framework in topological analysis of material structures.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2196-29951212025Natural Effects and Separable Effects: Insights into Mediation Analysis20ENEtsujiSuzukiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohiroShinozakiInterfaculty Initiative in Information Studies, the University of TokyoEijiYamamotoOkayama University of SciencePurpose of Review We compare natural effects and separable effects under nonparametric structural equation models with independent errors, highlighting their similarities and differences. By examining their required properties and sufficient conditions for identification, we aim to provide deeper insights into mediation analysis.<br>
Recent Findings If certain assumptions about confounding, positivity, and consistency are met, we can identify natural direct and indirect effects under nonparametric structural equation models with independent errors. However, these effects have been criticized because they rely on a specific cross-world quantity, and the so-called cross-world independence assumption cannot be empirically verified. Furthermore, interventions on the mediator may sometimes be challenging to even conceive. As an alternative approach, separable effects have recently been proposed and applied in mediation analysis, often under finest fully randomized causally interpretable structured tree graph models. These effects are defined without relying on any cross-world quantities and are claimed to be identifiable under assumptions that are testable in principle, thereby addressing some of the challenges associated with natural direct and indirect effects.<br>
Summary To conduct meaningful mediation analysis, it is crucial to clearly define the research question of interest, and the choice of methods should align with the nature of the question and the assumptions researchers are willing to make. Examining the underlying philosophical perspectives on causation and manipulation can provide valuable insights.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0003-68622025Comparison of flight behaviors among laboratory and field strains in Tribolium castaneum (Coleoptera: Tenebrionidae) using a simple method to measure flight abilityENSotaSoneFaculty of Environment, Life, Natural Science and Technology, Okayama UniversityTakahisaMiyatakeFaculty of Environment, Life, Natural Science and Technology, Okayama UniversityMost insects can fly. The acquisition of flight is a factor that allows insects to prosper on Earth. On the other hand, in the same species and population, individual differences in flight ability may occur. Flight ability can vary due to geographical conditions and cumulative rearing. Investigating these changes in flight performance is important for understanding dispersal polymorphism and the evolution of flight performance. Thus, in the present study, the flight behaviors between cumulative rearing and field strains and changes in flight behaviors between strains of the red flour beetle, Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), which is distributed around the world were compared. Tribolium castaneum is a worldwide pest of stored grains. Its body length is about 3–4 mm. Previous studies have investigated the influence of environmental and physiological factors on the flight of this species, but no studies have examined individual differences or polymorphism in flight behaviors within this species. In this study, we developed a simple apparatus that can quantify the flight behavior of this species. The experimental apparatus was set up as a double structure with two different size containers. This apparatus was able to assess the flight activity of insects by counting individuals in a big container because insects transfer to the big container only by flight. Moreover, upward flight ability was possible to be assessed by the apparatus adding the barrier. Then, the flight behavior was compared between strains of this species that have been bred in the laboratory for more than 45 years and several strains of this species collected in the field. The results showed no variation in flight activity between strains, but flying ability was higher in strains originating from warmer regions. Here, we discussed the variations in flight behavior of T. castaneum.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417102025Primary Lacrimal Sac Diffuse Large B-cell Lymphoma Treated With Local Radiotherapy Alone: A Case With No Relapse After 21 Years of Follow-Upe95411ENToshihikoMatsuoHealthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakehiroTanakaPathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMitsuhiroTakemotoRadiotherapy, Himeji Red Cross HospitalPrimary lacrimal sac lymphoma is rare and diagnosed as diffuse large B-cell lymphoma in a predominant histopathological type. Systemic chemotherapy would be the standard of care, but local radiotherapy may be a treatment option toward a localized lesion. The present patient is a 54-year-old otherwise healthy woman with a right lacrimal sac mass, which was proven by excisional biopsy to be diffuse large B-cell lymphoma. Since she did not have any other systemic lesions on gallium scintigraphy and neck-to-abdominal computed tomography scans, which were the standard procedure at that time, she underwent local radiotherapy at 40 Gy. Two years later, at the age of 56 years, she developed radiation retinopathy with macular edema in the right eye and had spotty laser photocoagulation in the nasal half of the fundus. At the age of 57 years, she developed radiation cataract and underwent cataract surgery with intraocular lens implantation in the right eye. At the age of 58 years, the macular edema in the right eye became worse and remained active, resulting in poor visual acuity of 0.1. She thus underwent 25-gauge vitrectomy in the right eye to peel off the adhering posterior vitreous surface, together with the internal limiting membrane, as the standard procedure at that time. The visual acuity in the right eye was elevated to 0.6. She maintained the visual acuity afterward and had no relapse of lymphoma in 21 years from the diagnosis of primary right lacrimal sac diffuse large B-cell lymphoma. Local radiotherapy would still be a treatment option for localized lymphoma lesions such as primary lacrimal sac lymphoma.No potential conflict of interest relevant to this article was reported.Springer Nature SwitzerlandActa Medica Okayama0302-97432025Effects of Visual Stimuli on Perceived Sound Volume in Virtual Reality Spaces286299ENYukiMatsudaOkayama UniversityTomaKobayashiNara Institute of Science and TechnologyHirokiWatanabeFuture University HakodateKeiichiYasumotoNara Institute of Science and TechnologyWith the proliferation of affordable and high-performance virtual reality (VR) devices, VR content such as games and the metaverse is becoming increasingly widespread. In VR environments, users experience various sensory stimuli, primarily through visual and auditory cues. However, subjective perception of these stimuli varies based on user context. Existing studies have shown that auditory perception can be influenced by visual stimuli, however, most of them have focused on congruent audiovisual stimuli, leaving the effects of non-congruent pairings unexplored. This study investigates how visual stimuli, specifically color and crowdedness, influence perceived sound volume in VR. In the experiment that participants experienced VR environments with different room colors while listening to test tones, the results showed that warm colors led to higher perceived volume at low sound levels. Also, in the experiment that participants viewed VR scenes with varying crowd densities while hearing announcements, less crowded environments resulted in higher perceived sound volume. These findings suggest that visual context impacts auditory perception, providing insights for optimizing hearable devices and enhancing VR auditory experiences.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1345-26302025Comparative analysis of interactions between five strains of Pseudomonas syringae pv. tabaci and Nicotiana benthamianaENYunaNakaoGraduate School of Medicine, Science and Technology, Shinshu UniversityShutaAsaiGraduate School of Environmental, Natural Science and Technology, Okayama UniversityHidenoriMatsuiGraduate School of Environmental, Natural Science and Technology, Okayama UniversityYukiIchinoseGraduate School of Environmental, Natural Science and Technology, Okayama UniversityShinpeiKatouGraduate School of Medicine, Science and Technology, Shinshu UniversityPseudomonas syringae pv. tabaci 6605 (Pta 6605), the agent of wildfire disease in tobacco, has been used as a model strain for elucidating the virulence mechanisms of Pta. However, the host genes involved in resistance or susceptibility to Pta remain largely unknown. Nicotiana benthamiana is a model plant species in the Solanaceae family and is useful in functional analyses of genes. We herein compared five Pta strains (6605, 6823, 7372, 7375, and 7380) in terms of their phenotypes on medium and interactions with N. benthamiana. Pta 6605 and Pta 6823 showed more active proliferation than the other strains in a high cell density culture. Moreover, Pta 6605 exhibited markedly higher swarming motility than the other strains. In inoculated leaves of N. benthamiana, Pta 6605 and Pta 6823 caused more severe disease symptoms and proliferated to a higher cell density than the other strains. However, Pta 6823 as well as Pta 7372 and Pta 7380 induced the high accumulation of salicylic acid (SA). Moreover, the inoculations of Pta 6823 and Pta 7372 resulted in the upregulation of ethylene biosynthesis genes. On the other hand, Pta 6605 induced neither SA accumulation nor the expression of ethylene biosynthesis genes, and suppressed the expression of jasmonate biosynthesis genes. Moreover, chlorosis was clearly induced in the upper uninoculated leaves of Pta 6605-infected plants. These results suggest that Pta 6605 escapes from or suppresses plant immune systems and, thus, is the most virulent on N. benthamiana among the five strains tested.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0929-19032025ATPase copper transporting beta contributes to cisplatin resistance as a regulatory factor of extracellular vesicles in head and neck squamous cell carcinomaENTatsuoOgawaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKishoOnoDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShojiRyumonDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoheiSatoDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKokiUmemoriDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKunihiroYoshidaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyoichiObataDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiKunisadaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTatsuoOkuiDepartment of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima UniversityKuniakiOkamotoDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFatemehMomen-HeraviDepartment of Orofacial Sciences, School of Dentistry, University of California San FranciscoSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCisplatin (CDDP) resistance remains a major clinical challenge in the treatment of head and neck squamous cell carcinoma (HNSC). Our group identified ATPase copper transporting beta (ATP7B) as a mediator of CDDP resistance through its role in drug efflux and small extracellular vesicle (sEV) secretion. Herein, we uncovered a novel mechanism by which ATP7B regulates sEV dynamics and the intercellular transmission of CDDP resistance. Using transcriptomic analyses of HNSC datasets, we demonstrate that ATP7B expression correlates with endocytosis- and epithelial-mesenchymal transition (EMT)-related gene sets and with elevated levels of EV-associated proteins. CDDP-resistant HNSC cells exhibited upregulated ATP7B, Rab5/Rab7, and preferentially secreted HSP90- and EpCAM-rich sEVs. These sEVs were leading to increased ATP7B expression and reduced CDDP sensitivity in recipient cells. A pharmacological inhibition of sEV biogenesis with GW4869 suppressed ATP7B and Atox1 expressions, inhibited late endosome maturation, and significantly enhanced CDDP-induced apoptosis in HNSC cells. In vivo, GW4869 reduced the sEV protein content and ATP7B expression in xenograft tumors. These findings establish that ATP7B is a critical modulator of sEV cargo and resistance propagation. Our results highlight a previously unrecognized ATP7B–sEV axis driving chemoresistance and identify sEV inhibition as a promising strategy to overcome therapeutic failure in HNSC.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0962-88193412025Highly efficient transgenesis mediated by Tip100 transposon system in medaka46ENYoshitakaTanakaUshimado Marine Institute (UMI), Okayama UniversityTakahideSekiDepartment of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku UniversityAtsushiHoshinoNational Institute for Basic BiologySatoshiAnsaiUshimado Marine Institute (UMI), Okayama UniversityTransgenesis mediated by transposon is an effective approach for introducing exogenous DNA into the nuclear genome and establishing stable transgenic strains that efficiently express genetic tools. Although the DNA transposon Tol2 is widely used for transgenesis in zebrafish, its endogenous transpositional activity can lead to unintended transgene mobilization, making it unsuitable for transgenesis in medaka (Oryzias latipes). Here, we demonstrated that the DNA transposon Tip100, originally identified in the common morning glory (Ipomoea purpurea), an ornamental plant, can serve as a useful tool for transgenesis in Japanese medaka. The GFP transgene cassette, when co-injected with Tip100 transposase mRNA, was expressed in significantly higher number of somatic cells in the injected fish. Furthermore, a transgene flanked by truncated recognition sequences (100 bp each) exhibited expression levels comparable to those of the original vector containing the full 2.2 kb recognition sequence. Injection of a transgene driven by a germline-specific promoter revealed that fish injected with Tip100 mRNA exhibited a significantly higher germline transmission rate (42/68; 62.7%) compared to those injected without the mRNA (13/62; 21.0%). We successfully established transgenic strains by outcrossing injected founders with GFP-positive germ cells (7/7; 100%) and demonstrated that the transgenes were randomly integrated into the medaka genome, generating 8-bp duplications at the insertional sites–an insertional signature of the hAT superfamily of transposons. Our findings indicate that the Tip100 system is a promising tool for generating stable transgenic strains that express various genetic tools in medaka and potentially other fish species.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1752-19471912025The safety and efficacy of finasteride for transgender men with androgenetic alopecia: a case series468ENYusukeTominagaDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTomokoKobayashiDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYukoMatsumotoDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTomokoSakoDepartment of Urology, Hiroshima City Hiroshima Citizens HospitalTakatoshiMoriwakeDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSatoshiHoriiDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakuyaSadahiraDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSatoshiKatayamaDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakehiroIwataDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShingoNishimuraDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKensukeBekkuDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKoheiEdamuraDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasamiWatanabeCenter for Innovative Clinical Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMotooArakiDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineBackground Testosterone replacement therapy is commonly used in transgender men for masculinization. One of the most common adverse effects of testosterone replacement therapy is androgenetic alopecia. In Japan, finasteride is approved exclusively for cisgender men and is not indicated for transgender men. The aim of this clinical trial was to evaluate the safety and efficacy of finasteride in transgender men with androgenetic alopecia.<br>
Case presentation This study included three transgender men (assigned female at birth, identifying as male), aged 44, 43, and 29 years. All participants were of Asian ethnicity. A clinical trial was conducted from October 2021 to December 2023. Transgender men aged 20–60 years who had not undergone hysterectomy, were undergoing testosterone replacement therapy, and who had been diagnosed with stage ≥ II androgenetic alopecia on the basis of the Norwood–Hamilton scale were recruited. The participants initiated treatment with 0.2 mg of finasteride per day for 3 months (phase 1). If no adverse events above grade 2 occurred, the dose was increased to 1.0 mg per day for an additional 3 months (phase 2). The primary endpoints were the incidence of treatment-related adverse events at 1 week, 1 month, and 3 months, as well as the rate of participants continuing treatment at 3 months. None of the patients experienced serious adverse events at 3 months, and all the patients extended their treatment to a total of 6 months. Improvements of at least one stage on the N–H scale were observed, but two participants experienced resumption of menstruation.<br>
Conclusion Finasteride appears to be a safe and effective treatment for androgenetic alopecia in transgender men undergoing testosterone replacement therapy. However, its potential for reducing some of the effects of testosterone replacement therapy warrants further investigation. Trial registration: jRCT, jRCTs061210040, registered 7 October 2021, https://jrct.mhlw.go.jp/latest-detail/jRCTs061210040.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1471-23692612025Risk of malignant neoplasms of tacrolimus in kidney transplant patients: a retrospective cohort study conducted using the Japanese National Database of Health Insurance Claims491ENRisaKubotaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-EiSadaDepartment of Clinical Epidemiology, Kochi Medical School, Kochi UniversityMotoTokunagaDepartment of Urology, National Hospital Organization Okayama Medical CenterKasumiYoshinagaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoakiYamanoiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsushiKawadaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeTominagaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaSadahiraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKatayamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakehiroIwataDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShingoNishimuraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKensukeBekkuDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiEdamuraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoKobayashiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiNakagawaDepartment of Urology, Juntendo University Graduate School of MedicineNaotsuguIchimaruDepartment of Urology, Kinki Central HospitalKoichiroWadaDepartment of Urology, Shimane University Faculty of MedicineMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Although the long-term survival of kidney transplant recipients has significantly improved, malignant neoplasms remain one of the leading causes of death in this population. The recipients face a 1.8-fold increased risk of developing malignant neoplasms compared with the general population. This risk increases with time after transplantation. Tacrolimus (TAC) is preferred over cyclosporine A (CyA) in terms of efficacy against organ rejection, but evidence on the risk of malignant neoplasms is lacking. We aimed to describe the incidence and types of malignant neoplasms in kidney transplant recipients and evaluate the association between malignant neoplasms development and the type of prescribed CNI.<br>
Methods: This retrospective cohort study was conducted using the Japanese National Database of Health Insurance Claims, including data covering 99% of kidney transplant patients in Japan. Patients who underwent kidney transplantation and were prescribed TAC or CyA between April and June 2011 were included. The primary outcome included the incidence of malignant neoplasms, and secondary outcomes included overall survival and graft survival.<br>
Results: A total of 7,590 patients were included, with 11.0% developing malignant neoplasms during the follow-up period. The most common malignant neoplasms were in the digestive organs and urinary tract. No statistically significant difference in malignant neoplasms incidence was observed between TAC and CyA users (hazards ratio: 0.97, 95% CI: 0.84 to 1.12; estimated average treatment effect: −24.05, 95% CI: −184.90 to 136.80). The patient and graft survival rates were also comparable between the groups.<br>
Conclusions: This large study suggests that TAC is not associated with an increased risk of malignant neoplasms compared to CyA in the late post-transplant period.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Periodontitis associated with Porphyromonas gingivalis infection is a risk factor for infertility through uterine hypertrophy34964ENChiakiKamei-NagataDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOmoriDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidefumiSakoDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalKyosukeSakaidaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalMasa-akiNakayamaDepartment of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokiMandaiDepartment of Pharmacy, Faculty of Pharmacy, Gifu University of Medical ScienceMoyukaKubota-TakamoriDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFumikoKiyamaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakayukiIshiiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKimitoHiraiDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsushiIkedaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalKazuTakeuchi-HatanakaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalYukiShinoda-ItoDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasakoTai-TokuzenDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalAiSakamotoCenter for Reproductive Medicine, Miyake ClinicMachikoKiyokawaCenter for Reproductive Medicine, Miyake ClinicTomomiYamanishiCenter for Reproductive Medicine, Miyake ClinicTakashiOdaCenter for Reproductive Medicine, Miyake ClinicMasayukiTakigawaMiyake Hello Dental Clinic, Pediatric Dentistry and OrthodonticsTadashiYamamotoThe Center for Graduate Medical Education (Dental Division), Okayama University HospitalTakahitoMiyakeCenter for Reproductive Medicine, Miyake ClinicShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPeriodontitis has recently been recognized as a potential risk factor for infertility due to its adverse effect on conception, although the underlying mechanisms remain unclear. This study investigated serum IgG antibody titers against periodontopathogenic bacteria in women with unexplained infertility and investigated how periodontal inflammation affects pregnancy and uterine function using a ligature-induced periodontitis mouse model infected with Porphyromonas gingivalis (Pg). IgG antibody titers against seven periodontopathogenic bacteria strains were measured by ELISA in 76 spontaneously pregnant women and 70 women undergoing infertility treatment. In the in vivo study, periodontitis mice were bred four weeks after periodontitis induction. Birth numbers, newborn weights, and gestation periods were assessed. To evaluate periodontal inflammation, alveolar bone, serum, and uterus was collected before mating. Uterine tissue was evaluated through histological and immunohistochemical staining. Women receiving infertility treatment were significantly older and had higher IgG titers against three Pg strains. Periodontitis mice had fewer births, lower newborn weights, and increased uterine cross-sectional areas. Additionally, elevated estrogen receptor α and progesterone receptor expression levels were observed in endometrial and stromal tissues. These results suggest that periodontitis may cause uterine hypertrophy and hormone receptor changes, potentially impairing pregnancy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1943-39218762025Implicit effect of visual long-term memory for nonverbal objects on recognition judgment18411851ENTomoeMasuokaFaculty of Nursing, Japanese Red Cross Hiroshima College of NursingMegumiNishiyamaDepartment of Criminal Psychology, University of Human EnvironmentsYunaTsurusakiFaculty of Education, Okayama UniversityTakafumiTerasawaFaculty of Education, Okayama UniversityThis study uses an indirect recognition procedure to examine whether prior exposure to nonverbal visual objects affects recognition judgments in later, unrelated recognition tests. We also examined the effect of matching operations between study and test on recognition judgments. The experiment consisted of two sessions. The first session was an incidental learning task: Each object was presented twice, and participants were asked to count the number of corners of the presented object. In the second session after 3 weeks, participants performed the same task as in the first session and then performed an unexpected recognition test. In this test, participants were asked to identify whether the presented object had appeared in the second session. To unify the operation between study and test, some participants were required to count the number of corners of the presented object before the recognition judgment. The results revealed that recognition performance for the objects that appeared in the first session was significantly different from that of objects that had not appeared, even when participants were not asked to recall the episode of the first session when performing the recognition test. Although the results of the effect of the matching operation suggested a negative effect on recognition, the results were unclear. This finding indicates that representations for nonverbal objects are preserved for at least 3 weeks. This also highlights the need to consider the implicit effect of a brief prior experience on recognition judgments.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0167-690310542025Effect of environmental conditions on seed germination and seedling growth in Cuscuta campestris11571167ENKokiNagaoGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTakuTakahashiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityRyusukeYokoyamaGraduate School of Life Sciences, Tohoku UniversityDodder (Cuscuta) is an obligate parasitic plant that cannot survive without a host and causes significant damage to crop yields. To understand its growth characteristics before parasitism, we examined the effects of environmental conditions on seed germination and seedling growth in Cuscuta campestris Yunck. Among various factors, we focused on the effects of light, pH, temperature, sugars, salts, hormones, amino acids and polyamines on seeds sown on agar plates. Regarding the effect of light on germination, far-red light was preferable rather than red light and the reversible response of seeds to red and far-red light was confirmed, implicating a phytochrome-mediated signaling pathway opposite to that in many seed plants. Among the amino acids, aspartic acid and alanine had a promotive effect, while histidine had an inhibitory effect on germination. We further found that, in addition to gibberellic acid, methyl jasmonate stimulated both germination and shoot elongation. While 2,4-D extended the viability of trichomes around the root cap, kinetin induced the formation of scale leaves on the shoot and undifferentiated cell clusters at the base of the shoot and root tip. Real-time reverse transcriptase PCR (RT-PCR) experiments confirmed that the expression of a putative RbcS gene for photosynthesis showed no response to light, whereas that of a Phytochrome A homolog increased in the dark. Our results indicate that some of the molecular mechanisms involved in responding to light and hormone signals are uniquely modified in dodder seedlings, providing clues for understanding the survival strategy of parasitic plants.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Continuous glucose monitoring reveals periodontitis-induced glucose variability, insulin resistance, and gut microbiota dysbiosis in mice34768ENMoyukaKubota-TakamoriDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOmoriDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChiakiKamei-NagataDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalFumikoKiyamaDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakayukiIshiiDepartment of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasaakiNakayamaDepartment of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuyoshiGotohDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesKimitoHiraiDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalYukiShinoda-ItoDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeisukeOkuboDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalShinNakamuraDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsushiIkedaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalTsugumichiSaitoDepartment of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei UniversityJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDiabetes mellitus (DM) management has advanced from self-monitoring blood glucose (SMBG) to continuous glucose monitoring (CGM), which better prevents complications. However, the influence of periodontitis—a common DM complication—on glucose variability is unclear. This study examined glucose variability in mice with periodontitis using CGM. Periodontitis was induced in 9-week-old male C57BL/6J mice via silk ligatures around the upper second molars. Glucose levels were monitored over 14 days with CGM, validated by SMBG. On day 14, samples were collected to assess alveolar bone resorption and serum levels of tumor necrosis factor-α (TNF-α), insulin, and amyloid A. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted to evaluate insulin resistance. Gut microbiota diversity was also analyzed. By day 10, mice with periodontitis exhibited higher mean glucose levels and time above range than controls. On day 14, serum insulin and amyloid A levels significantly increased, while TNF-α remained unchanged. GTT and ITT indicated insulin resistance. Microbiota analysis showed reduced alpha- and altered beta-diversity, with decreased Coprococcus spp. and increased Prevotella spp., linking dysbiosis to insulin resistance. Periodontitis disrupts glucose regulation by promoting insulin resistance and gut microbiota imbalance, leading to significant glucose variability.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-818417102025Refractive Error Correction With Glasses in Congenital Ocular Fundus Anomalies: A Retrospective Series of 18 Children With Different Disease Entities Followed Up for More Than 10 Yearse94062ENToshihikoMatsuoDepartment of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityObjectives: Children with congenital anomalies of the posterior segment of the eye are in the process of visual development, and thus, their refractive errors should be detected by cycloplegic refraction testing to prescribe full-correction glasses, if required, and to help their visual acuity develop with growth. This study aimed to review refractive correction in children with congenital ocular fundus anomalies.<br>
Methods: A retrospective review was conducted on 18 consecutive children (11 female and seven male children) who were diagnosed with ocular fundus anomalies and followed for 10 years or more by a single ophthalmologist at a referral-based hospital. The age at the initial visit ranged from 10 days after birth to 11 years, with a median of one year and four months, and the age at the last visit ranged from 10 to 32 years, with a median of 15 years. The follow-up periods ranged from 10 to 21 years at a median of 15 years.<br>
Results: The diagnoses were familial exudative vitreoretinopathy (FEVR) in eight children, persistent fetal vasculature (PFV) in five, morning glory disc anomaly in two, optic nerve and choroidal coloboma (CHARGE syndrome) in two, and Coats disease in one. Full-correction glasses were prescribed in eight children, while the remaining 10 children did not wear glasses. Among nine children with the uncorrected visual acuity of 1.0 or better in one eye and the visual acuity in the other eye ranging from light perception to 0.01, eight children did not wear glasses, and one child wore glasses with hyperopic correction. The diagnoses in these nine children were PFV in five children, morning glory disc anomaly in two, FEVR in one, and Coats disease in one. In seven children who wore full-correction glasses, the best corrected visual acuity in the better eye ranged from 0.2 to 0.9 at a median of 0.5. In contrast, the visual acuity in the other eye ranged from light perception to 0.1 at a median of 0.03. The diagnoses of these seven children were FEVR in five children and CHARGE syndrome in two. The five children with FEVR showed myopic astigmatism in both eyes, while the two children with CHARGE syndrome showed hyperopic astigmatism in both eyes.<br>
Conclusion: Children with unilateral eye anomalies such as PFV and morning glory disc anomaly did not wear glasses since their healthy eyes had good uncorrected visual acuity. In contrast, children with involvement of both eyes in FEVR and CHARGE syndrome wore full-correction glasses. Rough information regarding full-correction glasses in each category would help clinicians cope with rare congenital eye diseases. However, this conclusion is generally applicable to the standard practice of pediatric ophthalmology.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1573-72092842025Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma51ENMay WathoneOoDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakaoHikitaDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohaMashimaDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKosukeTorigataSchool of Medicine, Kobe UniversityYin MinThuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohiroHabuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalSachioItoDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHitoshiNagatsukaDepartment of Thoracic Surgery, National Hospital Organization, Shikoku Cancer CenterShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasanoriNakayamaDepartment of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDespite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1342-17512952025Development and validation of an algorithm for identifying patients undergoing dialysis from patients with advanced chronic kidney disease650661ENTakahiroImaizumiDepartment of Nephrology, Nagoya University Graduate School of MedicineTakashiYokotaInstitute of Health Science Innovation for Medical Care, Hokkaido University HospitalKoutaFunakoshiKyusyu University HospitalKazushiYasudaDepartment of Nephrology, Nagoya University Graduate School of MedicineAkikoHattoriDepartment of Nephrology, Nagoya University Graduate School of MedicineAkemiMorohashiDepartment of Advanced Medicine, Nagoya University HospitalTatsumiKusakabeInstitute of Health Science Innovation for Medical Care, Hokkaido University HospitalMasumiShojimaDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversitySayokoNagamineDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityToshiakiNakanoDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityYongHuangDivision of Medical Informatics, Okayama University HospitalHiroshiMorinagaDepartment of Comprehensive Therapy for Chronic Kidney Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMikiOhtaClinical Research Promotion Center, The University of Tokyo HospitalSatomiNagashimaDepartment of Healthcare Information Management, The University of Tokyo HospitalRyusukeInoueMedical Information Technology Center, Tohoku University HospitalNaokiNakamuraMedical Information Technology Center, Tohoku University HospitalHidekiOtaMedical Information Technology Center, Tohoku University HospitalTatsuyaMaruyamaClinical Research Promotion Center, The University of Tokyo HospitalHideoGobaraDivision of Medical Informatics, Okayama University HospitalAkiraEndohDepartment of Medical Informatics, Hokkaido University HospitalMasahikoAndoDepartment of Nephrology, Nagoya University Graduate School of MedicineYoshimuneShiratoriMedical IT Center, Nagoya University HospitalShoichiMaruyamaDepartment of Nephrology, Nagoya University Graduate School of MedicineBackground Identifying patients on dialysis among those with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2 remains challenging. To facilitate clinical research in advanced chronic kidney disease (CKD) using electronic health records, we aimed to develop algorithms to identify dialysis patients using laboratory data obtained in routine practice.<br>
Methods We collected clinical data of patients with an eGFR < 15 mL/min/1.73 m2 from six clinical research core hospitals across Japan: four hospitals for the derivation cohort and two for the validation cohort. The candidate factors for the classification models were identified using logistic regression with stepwise backward selection. To ensure transplant patients were not included in the non-dialysis population, we excluded individuals with the disease code Z94.0.<br>
Results We collected data from 1142 patients, with 640 (56%) currently undergoing hemodialysis or peritoneal dialysis (PD), including 426 of 763 patients in the derivation cohort and 214 of 379 patients in the validation cohort. The prescription of PD solutions perfectly identified patients undergoing dialysis. After excluding patients prescribed PD solutions, seven laboratory parameters were included in the algorithm. The areas under the receiver operation characteristic curve were 0.95 and 0.98 and the positive and negative predictive values were 90.9% and 91.4% in the derivation cohort and 96.2% and 94.6% in the validation cohort, respectively. The calibrations were almost linear.<br>
Conclusions We identified patients on dialysis among those with an eGFR < 15 ml/min/1.73 m2. This study paves the way for database research in nephrology, especially for patients with non-dialysis-dependent advanced CKD.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0957-45223612024Optical bandgap tuning in SnO2–MoS2 nanocomposites: manipulating the mass of SnO2 and MoS2 using sonochemical solution mixing6ENChinkhaiOngSchool of Engineering and Physical Sciences, Heriot-Watt University MalaysiaWeng NamLeeHeriot-Watt Global College, Heriot-Watt University MalaysiaYee SengTanSunway Biofunctional Molecules Discovery Centre, School of Medical and Life Sciences, Sunway UniversityPatrikOhbergSchool of Engineering and Physical Sciences, Institute of Photonics and Quantum Sciences, Heriot-Watt UniversityYasuhikoHayashiFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityTakeshiNishikawaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityYuenkiatYapHeriot-Watt Global College, Heriot-Watt University MalaysiaThis study investigates controlled optical bandgap tuning through precise adjustment of the SnO2 and MoS2 mass in nanocomposites. A sonochemical solution mixing method, coupled with bath sonication, is employed for the preparation of SnO2–MoS2 nanocomposite. This approach allows for comprehensive characterization using UV–Vis FTIR, XRD, EDX, Raman spectroscopies, and FESEM, providing insights into morphology, chemical, and optical properties. Increasing the SnO2 mass leads to a linear decrease in the optical bandgap energy, from 3.0 to 1.7 eV. Similarly, increasing the MoS2 mass also results in a decrease in the optical bandgap energy, with a limitation of around 2.01 eV. This work demonstrates superior control over optical bandgap by manipulating the SnO2 mass compared to MoS2, highlighting the complexities introduced by MoS2 2D nanosheets during sonication. These findings hold significant value for optoelectronic applications, emphasizing enhanced control of optical bandgap through systematic mass manipulation.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1875-83122025Computed tomography versus aortography for transcatheter patent ductus arteriosus closure in adultsENTakashiMikiDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToruMiyoshiDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTeijiAkagiDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMitsutakaNakashimaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineRieNakayamaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYoichiTakayaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKojiNakagawaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNorihisaTohDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineShinsukeYuasaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineAccurate sizing of the patent ductus arteriosus (PDA) is essential for successful transcatheter closure. While aortography is the standard imaging modality, computed tomography (CT) may offer superior anatomical visualization. This study aimed to compare the accuracy and procedural outcomes of preprocedural CT versus aortography alone in adult patients undergoing transcatheter PDA closure. We retrospectively analyzed 54 adult patients who underwent PDA closure using the Amplatzer™ Duct Occluder between 2009 and 2024. Nineteen patients were treated based on aortography alone and 35 based on preprocedural CT. We compared procedural characteristics and outcomes, including device size exchange and procedure time. A simulation study was also conducted in which two blinded implanters independently predicted occluder size based on CT and aortography, with actual implanted device size used as the reference. The CT group had significantly larger PDA sizes and implanted device sizes. Device replacement was required in three patients in the aortography group but none in the CT group. Procedure time was shorter in the CT group (60 ± 9 vs. 70 ± 14 min, p = 0.003). Simulation results showed that CT more accurately predicted the actual implanted device size (85% vs. 63%, p = 0.008). PDA size at the pulmonary artery end was significantly underestimated by aortography. Preprocedural CT improved procedural efficiency and device selection accuracy in adult PDA closure. These findings suggest that CT imaging may enhance planning and safety in transcatheter PDA interventions.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1757-65121612025Specific induction of right ventricular-like cardiomyocytes from human pluripotent stem cells519ENYukihiroSaitoDepartment of Cardiovascular Medicine, Okayama University HospitalKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University HospitalYukiKatanosakaDepartment of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesToshihiroIidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaiKusumotoDepartment of Biomedical Informatics and Molecular Biology, The Sakaguchi Laboratory, Keio University School of MedicineRyushiSatoDepartment of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of ShizuokaRikiAdachiDepartment of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of ShizuokaSatoshiShimizuDepartment of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of ShizuokaJunkoKurokawaDepartment of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of ShizuokaSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMoritaDepartment of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKeijiNaruseDepartment of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesMikakoNishidaDepartment of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHeiichiroUdonoDepartment of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJianhuaZhangDepartment of Medicine, University of Wisconsin School of Medicine and Public HealthShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTimothy J.KampDepartment of Medicine, University of Wisconsin School of Medicine and Public HealthHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesBackground Applications employing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) require well-characterized, chamber-specific hPSC-CMs. Distinct first heart field (FHF) and second heart field (SHF) cardiac progenitor populations give rise to the left ventricular (LV) and right ventricular (RV) cardiomyocytes, respectively. This developmental difference in cardiomyocyte origin suggests that chamber-specific cardiomyocytes have unique characteristics. Therefore, efficient strategies to differentiate human pluripotent stem cells (hPSCs) specifically to LV-like or RV-like cardiomyocytes are needed and it is still unknown whether there is a phenotypic difference between LV-like cardiomyocytes and RV-like cardiomyocytes derived from hPSCs.<br>
Methods An established hPSC cardiac differentiation protocol employing sequential GSK3β inhibition followed by Wnt inhibition (GiWi) was modified by addition of insulin or BMP antagonists during mesoderm formation. Cardiac progenitor populations were evaluated for FHF and SHF markers, and differentiated hPSC-CMs were characterized for chamber-specific markers.<br>
Results The GiWi protocol produced mainly FHF-like progenitor cells that gave rise to LV-like cardiomyocytes. Inhibition of endogenous BMP signaling during mesoderm induction using insulin or BMP antagonists reduced expression of FHF markers and increased expression of SHF markers in cardiac progenitor cells. hPSC-CMs arising from the SHF-like progenitor cells showed an RV-like gene expression pattern and exhibited phenotypic differences in spontaneous contraction rate, Ca2+ transients, and cell size compared to control LV-like cardiomyocytes.<br>
Conclusion This study establishes methodology to generate RV-like hPSC-CMs to support the development of disease modeling research using chamber-specific hPSC-CMs.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1618-12472025Establishment of a regenerative endodontic procedures model of mature mouse teeth and evaluation of the wound healing processENXiutingWangDepartment of Periodontology and Endodontology, Tohoku University Graduate School of DentistryShigekiSuzukiDepartment of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical SciencesShin-HoTsaiDepartment of Operative Dentistry, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical SciencesKarinNagasakiDepartment of Periodontology and Endodontology, Tohoku University Graduate School of DentistryRahmad RifqiFahrezaDepartment of Periodontology and Endodontology, Tohoku University Graduate School of DentistryMasatoOmoriDepartment of Periodontology and Endodontology, Tohoku University Graduate School of DentistrySatoruYamadaDepartment of Periodontology and Endodontology, Tohoku University Graduate School of DentistryAs the pulp regeneration for non-vital teeth is one of the ultimate clinical achievements, regenerative endodontic procedures (REPs) have become the most explored treatment modality. In this technique, periodontal tissue is guided from the apical region into the root canal and pulp chamber to promote attachment. It is well established that immature teeth are effective targets for treatment. However, the indications for this treatment have not yet expanded sufficiently to encompass mature teeth with closed apical apex. In the present study, a mouse model of REPs in mature teeth was established, employing the maxillary first molar mesial root. μCT analyses disclosed that the distance from the occlusal surface to the physiological apex of the maxillary first molar mesial root in mice is 2.14 mm ± 0.08 mm, and the distance from the occlusal surface to the periapical alveolar bone is 2.46 mm ± 0.10 mm. Mesial root canal was treated with several sizes of k-files, and 15# k-file was identified as the most suitable k-file for use (P = 0.0007). During the regenerative process, spindle-shaped fibroblast-like cells, fibrous tissue formation, and mineralized tissue formation were identified on days 14 and 28. This study demonstrated that it is feasible to use the maxillary first molar mesial root as a REPs model for mature teeth and provided a detailed protocol and analysis of the healing process.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2041-17231612025Persistent homology elucidates hierarchical structures responsible for mechanical properties in covalent amorphous solids8226ENEmiMinamitaniSANKEN, The University of OsakaTakenobuNakamuraDepartment of Materials and Chemistry Materials DX Research Center, National Institute of Advanced Industrial Science and Technology (AIST)IppeiObayashiCenter for Artificial Intelligence and Mathematical Data Science, Okayama UniversityHideyukiMizunoGraduate School of Arts and Sciences, The University of TokyoUnderstanding how atomic-level structures govern the mechanical properties of amorphous materials remains a fundamental challenge in solid-state physics. Under mechanical loading, amorphous materials exhibit simple affine and spatially inhomogeneous nonaffine displacements that contribute to the elastic modulus through the Born (affine) and nonaffine terms, respectively. The differences between soft local structures characterized by small Born terms or large nonaffine displacements have yet to be elucidated. This challenge is particularly complex in covalent amorphous materials such as silicon, where the medium-range order (MRO) plays a crucial role in the network structure. To address these issues, we combined molecular dynamics simulations with persistent homology analysis. Our results reveal that local structures with small Born terms are governed by short-range characteristics, whereas those with large nonaffine displacements exhibit hierarchical structures in which short-range disorder is embedded within the MRO. These hierarchical structures are also strongly correlated with low-energy localized vibrational excitations. Our findings demonstrate that the mechanical responses and dynamic properties of covalent amorphous materials are intrinsically linked to the MRO, providing a framework for understanding and tailoring their properties.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Pharmacokinetics and the effectiveness of pyrogen-free bioabsorbable wet adhesives20056ENRisaOshimaDepartment of Periodontology, Faculty of Dental Medicine, Hokkaido UniversityKumikoYoshiharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoNakanishiDepartment of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido UniversityTsukasaAkasakaDepartment of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido UniversityShinjiShimojiDepartment of Periodontology, Faculty of Dental Medicine, Hokkaido UniversityTeppeiNakamuraDepartment of Applied Veterinary Science, Faculty of Veterinary Medicine, Hokkaido UniversityTakumiOkiharaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityMarikoNakamuraDepartment of Clinical Psychology, School of Clinical Psychology, Kyushu University of Medical and ScienceAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIkkeiTamadaDepartment of Plastic and Reconstructive Surgery, Tokyo Metropolitan Children’s Medical CenterBartVan MeerbeekBIOMAT, Department of Oral Health Sciences, & UZ Leuven, Dentistry, KU LeuvenTsutomuSugayaDepartment of Periodontology, Faculty of Dental Medicine, Hokkaido UniversityYasuhiroYoshidaDepartment of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido UniversityBioabsorbable materials are essential for advanced therapies, including surgical sealing, cell therapy, and drug delivery. Natural bioabsorbable materials, including collagen and hyaluronic acid, have better biocompatibility than synthetic bioabsorbable polymers; however, they are mainly derived from animals, presenting infection risks. Non-animal origin polymers have a lower molecular weight than those of animal origins. Their viscosity increases with increase in molecular weight, making endotoxin removal difficult. Here, using the phosphoryl chloride disposal method, we present a strategy for synthesizing pyrogen-free bioabsorbable adhesives with controlled molecular weight. Phosphopullulan, a polysaccharide derivative, had less than detectable endotoxin levels and controllable average molecular weight of approximately 300,000 to over 1,400,000. Furthermore, it is important to ensure the safety as well as efficacy of bio-implantable materials. We have evaluated the biosafety of polysaccharide derivatives we are developing, and have examined their cell phagocytosis and pharmacokinetics in vitro and in vivo, and have confirmed that they are safe. We have also evaluated their adhesion to wet tissue adhesions and confirmed that they leak less than existing materials.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2041-17231612025Fully-gapped superconductivity with rotational symmetry breaking in pressurized kagome metal CsV3Sb53643ENX. Y.FengInstitute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter PhysicsZ.ZhaoInstitute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter PhysicsJ.LuoInstitute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter PhysicsY. Z.ZhouInstitute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter PhysicsJ.YangInstitute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter PhysicsA. F.FangH. T.YangInstitute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter PhysicsH.-J.GaoInstitute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter PhysicsR.ZhouInstitute of Physics, Chinese Academy of Sciences, and BeijingNational Laboratory for CondensedMatter PhysicsGuo-qingZhengDepartment of Physics, Okayama UniversityThe discovery of the kagome metal CsV3Sb5 has generated significant interest in its complex physical properties, particularly its superconducting behavior under different pressures, though its nature remains debated. Here, we performed low-temperature, high-pressure 121/123Sb nuclear quadrupole resonance (NQR) measurements to explore the superconducting pairing symmetry in CsV3Sb5. At ambient pressure, we found that the spin-lattice relaxation rate 1/T1 exhibits a kink at T ~ 0.4 Tc within the superconducting state and follows a T3 variation as temperature further decreases. This suggests the presence of two superconducting gaps with line nodes in the smaller one. As pressure increases beyond Pc ~ 1.85 GPa, where the charge-density wave phase is completely suppressed, 1/T1 shows no Hebel-Slichter peak just below Tc, and decreases rapidly, even faster than T5, indicating that the gap is fully opened for pressures above Pc. In this high pressure region, the angular dependence of the in-plane upper critical magnetic field Hc2 breaks the C6 rotational symmetry. We propose the s + id pairing at P > Pc which explains both the 1/T1 and Hc2 behaviors. Our findings indicate that CsV3Sb5 is an unconventional superconductor and its superconducting state is even more exotic at high pressures.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1472-68312512025Phosphorylated pullulan as a local drug delivery matrix for cationic antibacterial chemicals to prevent oral biofilm1333ENNaokoNamba-KoideDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalYasuhiroYoshidaDepartment of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido UniversityNoriyukiNagaokaAdvanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental SchoolTakumiOkiharaDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityYusukeKawataDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalMasahiroItoDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalTakashiItoCenter for Innovative Clinical Medicine, Okayama University HospitalKazuTakeuchi-HatanakaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalYukiShinoda-ItoDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOmoriDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTadashiYamamotoDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShogoTakashibaDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground Preventing oral infections, such as oral caries and periodontal disease, helps reduce the risks of various systemic diseases. In this study, the polysaccharide pullulan produced by the black yeast Aureobasidium pullulans was modified in combination with the cationic surfactant cetylpyridinium chloride (CPC) to create a local drug delivery system, and its antibacterial potential on oral bacteria was examined in vitro.<br>
Methods Pullulan was phosphorylated at the CH2OH residue of α6 in the maltotriose structure and mixed with CPC. Bacterial attachment of cariogenic Streptococcus mutans on hydroxyapatite plates (HAPs) treated with the phosphorylated pullulan (PP) and CPC compound (0.01% PP and 0.001– 0.03% CPC, and vice versa) was assessed by observing bacteria using a field emission scanning electron microscope (FE-SEM) and quantified through 16 S rRNA amplification via real-time polymerase chain reaction (PCR). Additionally, the quartz crystal microbalance (QCM) method was employed to evaluate the sustained release of CPC.<br>
Results PP-CPC compound maintained significant bactericidal activity even at 0.01%, which is one-fifth of the conventional applicable concentration of CPC. Additionally, a residual mixture was detected by the hydroxyapatite sensor of the crystal oscillator microbalance detector, suggesting an unknown molecular interaction that enables the sustained release of CPC after attachment to hydroxyapatite.<br>
Conclusions The combination of PP and CPC may contribute to the low concentration and effective prevention of oral infections, such as dental caries.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2399-3669712024Post-spinel-type AB2O4 high-pressure phases in geochemistry and materials science189ENMasakiAkaogiDepartment of Chemistry, Gakushuin UniversityTakayukiIshiiInstitute for Planetary Materials, Okayama UniversityKazunariYamauraResearch Center for Materials Nanoarchitectonics (MANA), National Institute for Materials SciencePost-spinel-type AB2O4 compounds are stable at higher pressures than spinel phases. These compounds have garnered much interest in geo- and materials science for their geochemical importance as well as potential application as high ionic conductors and materials with strongly correlated electrons. Here, large-volume high-pressure syntheses, structural features and properties of post-spinels are reviewed. Prospects are discussed for future searches for post-spinel-type phases by applying advanced large-volume high-pressure technology.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841792025Impact of a Peer-Led International Training Program on Work Motivation Among Early-Career Psychiatrists: A Mixed-Methods Studye93012ENToshihiroShimizuDepartment of Psychiatry, Saitama Prefectural Psychiatric HospitalJunkoKitaokaDepartment of Psychiatry, Fukkoukai Tarumi HospitalKenSuzutaniDepartment of Psychiatry, Aizu Medical CenterYutoSatakeDepartment of Psychiatry, The University of OsakaMasahideKodaCo-learning Community Healthcare Re-innovation Office, Graduate School of Medicine, Okayama UniversityIzumiKuramochiDepartment of Epileptology and Psychiatry, National Center of Neurology and PsychiatryNormanSartoriusPsychiatry, Association for the Improvement of Mental Health Programs (AIMHP)Background<br>
The Japan Young Psychiatrists Organization (JYPO) has conducted a Course for Academic Development of Psychiatrists (CADP), a peer-led residential international training program, since 2002 to promote the professional development of early-career psychiatrists. This study aimed to evaluate the impact of CADP on participants' work motivation using a psychometric scale and to identify the factors contributing to these changes.<br>
Methods<br>
We conducted a mixed-method study with 23 Japanese participants of the 21st CADP from March 8 to 10, 2024, in Himeji, Japan. Work motivation was assessed using the abbreviated version of the Measure of Multifaceted Work Motivations (MWM-12) at two time points: two weeks before and three months after the course. The total and subitem scores of the MWM-12 were analyzed using the Wilcoxon signed-rank test. Furthermore, free-text responses collected before and after the course were subjected to qualitative analyses.<br>
Results<br>
Significant improvements were observed in the MWM-12 total score from pre-course to post-course. Significant increases were also identified in specific sub-items: M1 (directionality of achievement-oriented motivation), M4 (directionality of competition-oriented motivation), M6 (sustainability of competition-oriented motivation), and M9 (sustainability of cooperation-oriented motivation). Qualitative analysis revealed changes in key categories, including growth as a psychiatrist, personal networking, personal growth, and increased motivation. The integration of quantitative and qualitative findings suggested that enhanced career perspectives (M1), professional growth and peer interaction (M4), and increased self-confidence and support networks (M6 and M9) contributed to improved motivation.<br>
Conclusion<br>
This study demonstrated that a three-day, two-night peer-led training program positively influenced work motivation among early-career psychiatrists.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2731-0590492025Heart failure-specific cardiac fibroblasts contribute to cardiac dysfunction via the MYC–CXCL1–CXCR2 axis11351151ENJinKomuroDepartment of Cardiology, Keio University School of MedicineHisayukiHashimotoDepartment of Cardiology, Keio University School of MedicineToshiomiKatsukiDepartment of Cardiology, Keio University School of MedicineDaiKusumotoDepartment of Cardiology, Keio University School of MedicineManamiKatohDepartment of Frontier Cardiovascular Science, Graduate School of MedicineToshiyukiKoDepartment of Frontier Cardiovascular Science, Graduate School of MedicineMasamichiItoDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of TokyoMikakoKatagiriDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of TokyoMasayukiKubotaDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of TokyoShintaroYamadaDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of TokyoTakahiroNakamuraDepartment of Cardiology, Keio University School of MedicineYoheiAkibaDepartment of Cardiology, Keio University School of MedicineThukaaKoukaDepartment of Cardiology, Keio University School of MedicineKaorukoKomuroDepartment of Cardiology, Keio University School of MedicineMaiKimuraDepartment of Cardiology, Keio University School of MedicineShogoItoDepartment of Cardiology, Keio University School of MedicineSeitaroNomuraDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of TokyoIsseiKomuroDepartment of Frontier Cardiovascular Science, Graduate School of MedicineKeiichiFukudaDepartment of Cardiology, Keio University School of MedicineShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiIedaDepartment of Cardiology, Keio University School of MedicineHeart failure (HF) is a growing global health issue. While most studies focus on cardiomyocytes, here we highlight the role of cardiac fibroblasts (CFs) in HF. Single-cell RNA sequencing of mouse hearts under pressure overload identified six CF subclusters, with one specific to the HF stage. This HF-specific CF population highly expresses the transcription factor Myc. Deleting Myc in CFs improves cardiac function without reducing fibrosis. MYC directly regulates the expression of the chemokine CXCL1, which is elevated in HF-specific CFs and downregulated in Myc-deficient CFs. The CXCL1 receptor, CXCR2, is expressed in cardiomyocytes, and blocking the CXCL1–CXCR2 axis mitigates HF. CXCL1 impairs contractility in neonatal rat and human iPSC-derived cardiomyocytes. Human CFs from failing hearts also express MYC and CXCL1, unlike those from controls. These findings reveal that HF-specific CFs contribute to HF via the MYC–CXCL1–CXCR2 pathway, offering a promising therapeutic target beyond cardiomyocytes.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0003-6072118102025Duganella hordei sp. nov., Duganella caerulea sp. nov., and Duganella rhizosphaerae sp. nov., isolated from barley rhizosphere146ENKatsumotoKishiroInstitute of Plant Science and Resources, Okayama UniversityNurettinSahinEgitim Fakultesi, Mugla Sitki Kocman UniversityDaisukeSaishoInstitute of Plant Science and Resources, Okayama UniversityNaokiYamajiInstitute of Plant Science and Resources, Okayama UniversityJunYamashitaInstitute of Plant Science and Resources, Okayama UniversityYukiMondenGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTomoyukiNakagawaFaculty of Applied Biological Sciences, Gifu UniversityKeiichiMochidaRIKEN Center for Sustainable Resource ScienceAkioTaniInstitute of Plant Science and Resources, Okayama UniversityDuganella sp. strains R1T, R57T, and R64T, isolated from barley roots in Japan, are Gram-stain-negative, motile, rod-shaped bacteria. Duganella species abundantly colonized barley roots. Strains R1T, R57T, and R64T were capable of growth at 4 °C, suggesting adaptation to colonize winter barley roots. Strains R57T and R64T formed purple colonies, indicating violacein production, while strain R1T did not. Based on 16S rRNA gene sequence similarities, strains R1T, R57T, and R64T were most closely related to D. violaceipulchra HSC-15S17T (99.10%), D. vulcania FT81WT (99.45%), and D. violaceipulchra HSC-15S17T (99.86%), respectively. Their genome sizes ranged from 7.05 to 7.38 Mbp, and their genomic G+C contents were 64.2–64.7%. The average nucleotide identity and digital DNA–DNA hybridization values between R1T and D. violaceipulchra HSC-15S17T, R57T and D. vulcania FT81WT, R64T and D. violaceipulchra HSC-15S17T were 86.0% and 33.2%, 95.7% and 67.9%, and 92.7% and 52.6%, respectively. Their fatty acids were predominantly composed of C16:0, C17:0 cyclo, and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). Based on their distinct genetic and phenotypic characteristics, and supported by chemotaxonomic analyses, we propose that strains R1T, R57T, and R64T represent novel species within the Duganella genus, for which the names Duganella hordei (type strain R1T = NBRC 115982 T = DSM 115069 T), Duganella caerulea (type strain R57T = NBRC 115983 T = DSM 115070 T), and Duganella rhizosphaerae (type strain R64T = NBRC 115984 T = DSM 115071 T) are proposed.No potential conflict of interest relevant to this article was reported.Springer Nature SwitzerlandActa Medica Okayama0303-42162025Low-Threshold Raman Silicon Lasers Using Photonic Crystal High-Q Nanocavities95143ENYasushiTakahashiOkayama UniversityTakashiAsanoKyoto UniversitySusumuNodaKyoto UniversityBy utilizing stimulated Raman scattering, it is possible to generate continuous-wave laser light in silicon, an indirect bandgap semiconductor. The first part of this chapter explains the mechanism of the Raman laser using a silicon resonator with a high-quality factor (Q). In the second part, the mechanism of the ultra-low threshold Raman silicon laser using a photonic crystal high-Q nanocavity is summarized, and recent advancements are explained.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72572025A case of retrograde colonic intussusception by tubulovillous adenomaENMichikoIkiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyoheiShojiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshitakaKondoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction Retrograde colonic intussusception is a rare condition in adults, often caused by organic lesions such as tumors. Autonomic dysfunction in disorders like multiple system atrophy (MSA) might contribute to its occurrence.<br>
Case presentation An 81-year-old bedridden woman with a history of MSA presented with severe abdominal pain and abdominal distension lasting 4 days. She had chronic severe constipation managed with laxatives and manual disimpaction. CT imaging revealed retrograde intussusception of the rectum into the sigmoid colon. Endoscopic reduction was attempted but was unsuccessful due to scope impassability. Emergency laparotomy identified a 4–5 cm tumor at the lead point, and manual reduction resulted in bowel perforation. Hartmann’s procedure with D2 lymphadenectomy was performed. The tumor was histopathologically diagnosed as a tubulovillous adenoma with no malignant features. The patient’s postoperative recovery was uneventful except for a urinary tract infection (Clavien–Dindo Grade II), and she was transferred to a rehabilitation facility on postoperative day 24.<br>
Conclusion Failure of reduction by air enema should raise suspicion for retrograde intussusception, warranting prompt surgery if an organic lead point is suspected.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1475-28672512025Precise stratification of prognosis in pancreatic ductal adenocarcinoma patients based on pre- and postoperative genomic information305ENKokichiMiyamotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKunitoshiShigeyasuDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuhiroYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceToshiakiTakahashiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaMoriwakeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasashiKayanoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYasuoNagaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHidekiYamamotoDepartment of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHironariKatoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMizukiMoritaDepartment of Biomedical Informatics, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health SystemsMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate among all cancers; hence, multidisciplinary treatment is essential for patients with PDAC. Although the resectability status, tumour marker, KRAS circulating tumour DNA (mutKRAS-ctDNA) mutations, and GATA binding 6 (GATA6) expression status are promising prognostic biomarkers, their effective integration before and after surgery remains unclear.<br>
Methods In this retrospective cohort study, patients with PDAC who had undergone radical resection were enrolled, and pre- and postoperative independent factors associated with poor prognosis were identified using Cox hazard modelling. Risk stratification systems were developed using the identified prognostic factors and investigated for the ability to predict prognosis.<br>
Results A total of 91 patients with PDAC were included (median follow-up duration, 28 months). Borderline resectable or locally advanced cancer at diagnosis, elevated carbohydrate antigen 19–9 (CA19-9) level, and mutKRAS-ctDNA-positive status were identified as independent preoperative factors associated with poor prognosis. The postoperative factors significantly associated with shorter overall survival were low GATA6 expression, elevated CA19-9 level, and mutKRAS-ctDNA-positive status. Finally, the preoperative and postoperative risk scoring systems developed using Cox modelling hazard ratio values could significantly stratify prognosis after curative resection for PDAC.<br>
Conclusion A risk stratification system based on liquid biopsy, specialised for each phase (pre- and post-surgery), has been proven to be a useful, simple, and practical prognostic prediction clinical tool to determine the optimal multidisciplinary treatment protocol for PDAC.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1071-26902025S100A8/A9-MCAM signaling promotes gastric cancer cell progression via ERK-c-Jun activationENYouyiChenDepartment of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of MedicineXuYangDepartment of Pathology, The First Affiliated Hospital, Zhejiang University School of MedicineRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBoPanThe First Affiliated Hospital, Zhejiang University School of MedicineFangpingWuSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical UniversityXuZhangDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineKazumiSagayamaFaculties of Educational and Research Management Field, Okayama UniversityBeiSunDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical UniversityMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesS100 protein family members S100A8 and S100A9 function primarily as a heterodimer complex (S100A8/A9) in vivo. This complex has been implicated in various cancers, including gastric cancer (GC). Recent studies suggest that these proteins play significant roles in tumor progression, inflammation, and metastasis. However, the exact mechanisms by which S100A8/A9 contributes to GC pathogenesis remain unclear. This study investigates the role of S100A8/A9 and its receptor in GC. Immunohistochemical analysis was performed on GC tissue samples to assess the expression of the S100A8/A9 receptor melanoma cell adhesion molecule (MCAM). In vitro transwell migration and invasion assays were used to evaluate the motility and invasiveness of GC cells. Cell proliferation was assessed using a growth assay, and Western blotting (WB) was employed to examine downstream signaling pathways, including ERK and the transcription factor c-Jun, in response to S100A8/A9–MCAM interaction. S100A8/A9 stimulation enhanced both proliferation and migration through MCAM binding in GC cell lines. These cellular events were accompanied by ERK activation and c-Jun induction. Downregulation of MCAM suppressed both ERK phosphorylation and c-Jun expression, highlighting the importance of the S100A8/A9‒MCAM‒ERK‒c-Jun axis in promoting GC progression. These findings indicate that S100A8/A9 contributes to GC progression via MCAM, which activates the ERK‒c-Jun pathway. The S100A8/A9‒signaling axis may represent a novel therapeutic target in GC.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1609-09852025An Alternative Approach Based on Skin Electrical Impedance to Determine Transepidermal Water Loss for Skin Barrier Function AssessmentsENOsamuUeharaDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityTakaoNakamuraDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityPurpose: The transepidermal water loss (TEWL) has long been measured as an indicator to assess the skin barrier function in dermatological research and clinical practice. However, practical limitations such as time requirement, environmental sensitivity, and measurement complexity hinder the widespread uptake of conventional TEWL measurements in clinical settings and routine monitoring. Consequently, there is a growing need for rapid, robust, and clinically applicable alternatives to conventional TEWL measurements. Here, we present a simple, non-invasive, and time-efficient method based on the skin electrical impedance for skin barrier function assessments.<br>
Methods: The skin electrical impedance, TEWL, stratum corneum (SC) thickness, and SC surface water content of 25 healthy adult participants with no history of dermatological diseases were measured at two adjacent forearm sites: intact site with a normal skin barrier and tape-stripped site with an impaired skin barrier. The measured impedance was used to calculate the SC thickness and surface water content, from which the TEWL was estimated and then compared against the TEWL measured using a Tewameter. The estimation accuracy was evaluated by determining the correlation coefficient (R) and root mean square error (RMSE) between estimated and measured TEWL.<br>
Results: A strong correlation (R = 0.891) was observed between estimated and measured TEWL, with an RMSE of 6.05 g/m²/h, indicating high accuracy of the proposed method.<br>
Conclusion: This impedance-based method provides accurate estimations of the TEWL, indicating its potential as a practical alternative to conventional TEWL measurements for skin barrier function assessments, particularly in clinical or high-throughput settings.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Prevalence of Streptococcus mutans harboring the cnm gene encoding cell surface protein Cnm in Japanese children27047ENYutoSuehiroDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaMakotoOkudaDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaMasatoshiOtsuguDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaMarinOchiaiDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaMisatoTakagiDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaFumikazuTojoDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaYusukeMikasaDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaShuheiNakaDepartment of Pediatric Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMichiyoMatsumoto-NakanoDepartment of Pediatric Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJinthanaLapirattanakulDepartment of Oral Microbiology, Faculty of Dentistry, Mahidol UniversityRenaOkawaDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaRyotaNomuraDepartment of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityKazuhikoNakanoDepartment of Pediatric Dentistry, Graduate School of Dentistry, The University of OsakaDental caries is a highly prevalent infectious disease primarily caused by the pathogenic bacterium Streptococcus mutans, which has also been associated with systemic disease. A 120-kDa collagen-binding protein (Cnm) produced by S. mutans contributes to cardiovascular disease pathogenicity. Few studies have addressed the current prevalence of S. mutans and the cnm gene in Japanese children or examined caries pathology in relation to cnm presence. Here, we investigated the prevalence of S. mutans and the distribution of cnm-positive S. mutans among 490 children who visited two university hospitals in Japan. The caries experience index (dmft/DMFT) was calculated, and the collagen-binding ability of cnm-positive S. mutans strains was assessed. S. mutans was isolated from the oral cavities of 158 patients (36.8%); 10.1% (16/158) harbored cnm-positive S. mutans. When caries experience indices were compared across dentitions, patients harboring cnm-positive strains had significantly higher dmft/DMFT scores than those with cnm-negative strains (P < 0.05). Additionally, a positive correlation was observed between the collagen-binding capacity of cnm-positive S. mutans and the dmft/DMFT score (r = 0.601, P < 0.05). These findings suggest that cnm contributes to caries progression through collagen-mediated adherence to tooth surfaces. The presence of cnm-positive S. mutans may represent a risk factor for increased caries susceptibility in children.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-72572025Metachronic development of cholangiocarcinoma during treatment for IgG4-related sclerosing cholangitisENKosakuMorimotoDepartment of Internal Medicine, Tsuyama Chuo HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalTakakiOkuyamaDepartment of Internal Medicine, Tsuyama Chuo HospitalShogoKimuraDepartment of Internal Medicine, Tsuyama Chuo HospitalKensukeTakeiDepartment of Internal Medicine, Tsuyama Chuo HospitalTakuyaSatomiDepartment of Internal Medicine, Tsuyama Chuo HospitalTsuyoshiOkadaDepartment of Surgery, Tsuyama Chuo HospitalSusumuShinouraDepartment of Surgery, Tsuyama Chuo HospitalReiShibataDepartment of Diagnostic Pathology, Tsuyama Chuo HospitalRyutaTakenakaDepartment of Internal Medicine, Tsuyama Chuo HospitalWe report a case of obstructive jaundice due to recurrent distal biliary stricture during 3 years of treatment for immunoglobulin G4 (IgG4)-related sclerosing cholangitis (IgG4-SC) associated with autoimmune pancreatitis. Although a relapse of IgG4-SC was initially suspected, imaging findings, laboratory tests, and histopathological examinations led to the diagnosis of metachronous cholangiocarcinoma. The patient underwent pancreaticoduodenectomy, and no cancer recurrence was noted 6 months postoperatively. Distal cholangiocarcinoma and IgG4-SC remission were observed in the resected specimen. In patients with recurrent biliary strictures during IgG4-SC treatment, comprehensive evaluations are essential because of the risk of disease relapse and development of metachronous cholangiocarcinoma.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2057-38041112025Time dependent predictors of cardiac inflammatory adverse events in cancer patients receiving immune checkpoint inhibitors40ENMichaelSayerSchool of Pharmacy & Pharmaceutical Sciences, University of CaliforniaHirofumiHamanoDepartment of Pharmacy, Okayama University HospitalMisakoNagasakaDivision of Hematology and Oncology, University of CaliforniaBenjamin J.LeeDepartment of Pharmacy, University of California Irvine HealthJeanDohDepartment of Pharmacy, University of California Irvine HealthPranav M.PatelDivision of Cardiology, Department of Medicine, University of CaliforniaYoshitoZamamiDepartment of Pharmacy, Okayama University HospitalAya F.OzakiSchool of Pharmacy & Pharmaceutical Sciences, University of CaliforniaBackground: Cardio-inflammatory immune related adverse events (irAEs) while receiving immune checkpoint inhibitor (ICI) therapy are particularly consequential due to their associations with poorer treatment outcomes. Evaluation of predictive factors of these serious irAEs with a time dependent approach allows better understanding of patients most at risk.<br>
Objective: To identify different elements of patient data that are significant predictors of early and late-onset or delayed cardio-inflammatory irAEs through various predictive modeling strategies.<br>
Methods: A cohort of patients receiving ICI therapy from January 1, 2010 to May 1, 2022 was identified from TriNetX meeting inclusion/exclusion criteria. Patient data collected included occurrence of early and later cardio-inflammatory irAEs, patient survival time, patient demographic information, ICI therapies, comorbidities, and medication histories. Predictive and statistical modeling approaches identified unique risk factors for early and later developing cardio-inflammatory irAEs.<br>
Results: A cohort of 66,068 patients on ICI therapy were identified in the TriNetX platform; 193 (0.30%) experienced early cardio-inflammatory irAEs and 175 (0.26%) experienced later cardio-inflammatory irAEs. Significant predictors for early irAEs included: anti-PD-1 therapy at index, combination ICI therapy at index, and history of peripheral vascular disease. Significant predictors for later irAEs included: a history of myocarditis and/or pericarditis, cerebrovascular disease, and history of non-steroidal anti-inflammatory medication use.<br>
Conclusions: Cardio-inflammatory irAEs can be divided into clinically meaningful categories of early and late based on time since initiation of ICI therapy. Considering distinct risk factors for early-onset and late-onset events may allow for more effective patient monitoring and risk assessment.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1939-59812025MATERIAL PROPERTIES OF DIE-CASTING DIE AROUND HEAT-CHECKING CREATED BY A HIGH-PRESSURE ALUMINUM ALLOY DIE-CASTING OPERATIONENMitsuhiroOkayasuDepartment of Mechanical Systems Engineering, Okayama UniversityJunyaShimazuDepartment of Mechanical Systems Engineering, Okayama UniversityIn this study, the material properties of a nitride die-casting die exhibiting heat-checking after the die-casting process were experimentally investigated using various methods. Based on the obtained results, the authors believe that several possible mechanisms underlying the formation of heat-checking can be identified. The microstructure of the die-casting die near the heat-checking region is characterized by equiaxed grains along the vicinity of the prior γ-grain boundaries, resulting from the lath martensitic formation. Additionally, numerous Cr–Mo–V-based nitride particles, approximately 100 nm in diameter, are precipitated. The surface hardness of the die-casting die, enhanced by nitriding, induces compressive residual stresses and increases adhesive forces. As a result of changes in microstructural characteristics and crack formation, the stress state near the die-casting die is altered, where compressive residual stresses, observed in the die-casting die, are released, leading to the tensile residual stresses. This phenomenon could accelerate the formation of a large number of heat-checking cracks.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Lactose fermenting enteroinvasive Escherichia coli from diarrhoeal cases confers enhanced virulence24040ENDebjaniGhoshDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)ProlayHalderDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)ProsenjitSamantaDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)GoutamChowdhuryCollaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute for Research in Bacterial InfectionsSreejaShawDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)PujaBoseDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)DeboleenaRoyDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)NiveditaRoyDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)KeiKitaharaCollaborative Research Centre of Okayama University for Infectious Diseases, ICMR-National Institute for Research in Bacterial InfectionsThandavarayanRamamurthyDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)HemantaKoleyDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)Shin-ichiMiyoshiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShantaDuttaDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)Asish KumarMukhopadhyayDivision of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI)Enteroinvasive Escherichia coli (EIEC), known for causing bacillary dysentery akin to Shigella species, comprises both lactose-fermenting (LF) and non-lactose-fermenting (NLF) isolates. While NLF-EIEC is a well-established pathogen associated with acute dysentery and harbours classical Shigella-like virulence factors, the role of LF-EIEC in human disease remains underexplored. In this study, we sought to characterize LF-EIEC clinical isolates and assessed their pathogenic potential in comparison to NLF-EIEC. Among 13,682 diarrhoeal stool specimens, six LF and nine NLF-EIEC were isolated, predominantly belonging to serogroups O28ac, O125, O136, and O152. Unlike other E. coli, all the EIEC isolates were non-motile. Both the types of EIEC had multiple plasmids harbouring several virulence encoding genes (ipaBCD, ial, virF, sig, sepA and ipaH). Resistance to recent generation antibiotics were mostly confined to NLF-EIEC but some of the LF-EIEC were resistant only to ceftriaxone. Higher invasion ability and significant increase in the expression of virulence encoding genes by the LF-EIEC (p < 0.05) were noted during infection to Int407 cell-line. Additionally, LF-EIEC exhibited extensive colonization of the mouse intestine and expressed severe keratoconjunctivitis in guinea pigs. Together, our findings highlight LF-EIEC as an emerging pathogenic variant warranting heightened surveillance and comprehensive investigation to better understand its epidemiological and clinical significance.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2057-39951012025Bioengineered chondrocyte-products from human induced pluripotent stem cells are useful for repairing articular cartilage injury in minipig modelENShotaTakihiraDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokaTakaoDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiFujisawaDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeYamadaDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShojiroHanakiDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohiroInoueDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShigeoOtakeDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkiYoshidaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazukiYamadaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiMiyazawaDepartment of Orthopaedic Surgery, National Hospital Organization Fukuyama Medical CenterEijiNakataDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakeshiTakaradaDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe capacity of articular cartilage for self-repair is limited. Therefore, wide-ranging cartilage damage rarely resolves spontaneously, leading to the development of osteoarthritis. Previously, we developed human-induced pluripotent stem cell (hiPSC)-derived expandable human limb-bud-like mesenchymal (ExpLBM) cells with stable expansion and high chondrogenic capacity. In this study, various forms of articular cartilage-like tissue were fabricated using ExpLBM technology and evaluated to examine their potential as biomaterials. ExpLBM cells derived from hiPSCs were used to produce particle-like cartilage tissue and plate-like cartilage tissue. The cartilaginous particles and cartilaginous plates were transplanted into a minipig osteochondral defect model, and cartilage engraftment was histologically evaluated. For both transplanted cartilaginous particles and cartilaginous plates, good Safranin O staining and integration with the surrounding tissue were observed. Cartilaginous particles and cartilaginous plates made using hiPSCs-derived ExpLBM cells are effective for the regeneration of cartilage after injury.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0947-839613192025Optical and chemical properties of silver tree-like structure treated with gold galvanic substitution744ENKazushiHondaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityNobuyukiTakeyasuGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityGalvanic gold substitution was executed in the presence of trisodium citrate on silver tree-like structures. No discernible difference in geometry was observed between the pre- and post-gold substitution phases, which benefited from the presence of citrate ions. The extent of gold substitution was regulated by the amount of gold ion solution added. After the gold substitution, an increase in extinction was observed in the ultraviolet region, indicating that gold was deposited at the surface. Raman scattering of para-toluenethiol was measured on the gold/silver tree-like structures at 488 nm excitations, where a decrease in the Raman peak intensity was observed as the quantity of gold ion solution increased. The results indicated that the optical property of silver was lost due to the increase of the amount of gold deposition. Concurrently, an investigation was conducted into the chemical resistance of the gold/silver tree-like structures, which was evaluated by measuring the resistivity inverse-proportional to the amount of silver ions dissolved by the diluted nitric acid. As the amount of gold ion solution added increased, the resistivity increased and became constant. The result implied that the surface chemical property had undergone a complete transformation into gold.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96252025Neutrophil-to-lymphocyte ratio affects the impact of proton pump inhibitors on efficacy of immune checkpoint inhibitors in patients with non‑small-cell lung cancerENTomokiHoriDepartment of Pharmacy, Nara Prefecture General Medical CenterKazuhiroYamamotoDepartment of Integrated Clinical and Basic Pharmaceutical Science, Okayama UniversityTakefumiItoDepartment of Respiratory Medicine, Nara Prefecture General Medical CenterShigekiIkushimaDepartment of Pharmacy, Nara Prefecture General Medical CenterTomohiroOmuraDepartment of Pharmacy, Kobe University HospitalIkukoYanoDepartment of Pharmacy, Kobe University HospitalBackground The neutrophil-to-lymphocyte ratio (NLR) at the initiation of immune checkpoint inhibitor (ICI) therapy is a known predictor of prognosis. Proton pump inhibitors (PPIs) reportedly attenuate the therapeutic efficacy of ICIs. However, the attenuation effects are not consistently observed across all patients. This study aimed to evaluate whether NLR serves as a stratification factor to determine the impact of PPI on the efficacy of ICI.<br>
Methods This retrospective study was conducted in patients with NSCLC treated with ICI monotherapy. Patients were stratified into two groups (higher NLR (≥ 4) and lower NLR (< 4)). PPI use was defined as the administration of PPIs within 30 days before or after ICI initiation. The primary outcome was progression-free survival (PFS) and the secondary outcome was overall survival (OS).<br>
Results Among the 132 patients included, PPI users exhibited significantly shorter median PFS and OS than non-PPI users. In the higher NLR group (n = 61), PPI users had a markedly shorter PFS and OS than non-PPI users (median PFS: 1.6 vs. 8.2 months; p < 0.01, median OS: 3.3 vs. 19.6 months; p = 0.015). Conversely, in the lower NLR group (n = 71), no significant difference in PFS and OS was observed between PPI users and non-PPI users (median PFS: 2.8 vs. 7.3 months, p = 0.83, median OS: 17.6 vs. 24.4 months, p = 0.40).<br>
Conclusion NLR may be a significant stratification factor for evaluating the impact of PPI on PFS and OS in patients with NSCLC undergoing ICI monotherapy.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1432-053314912025Cerebral Braak stage and amygdala granular fuzzy astrocyte status have independent effects on neuronal 3R-tau and 4R-tau accumulations in the olfactory bulb, respectively, in cases with low to intermediate AD neuropathologic change36ENOsamuYokotaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoMikiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHanaeNakashima-YasudaOkayama University Medical SchoolHidekiIshizuOkayama University Medical SchoolTakashiHaraguchiDepartment of Neurology, National Hospital Organization Minami-Okayama Medical CenterAkinoriMiyashitaDepartment of Molecular Genetics, Brain Research Institute, Niigata UniversityTakeshiIkeuchiDepartment of Molecular Genetics, Brain Research Institute, Niigata UniversityMasatoHasegawaDementia Research Project, Tokyo Metropolitan Institute of Medical ScienceNaotoNishikawaDepartment of Neuropsychiatry, Okayama University HospitalShintaroTakenoshitaDepartment of Neuropsychiatry, Okayama University HospitalSeishiTeradaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841782025Craniofacial Fibrous Dysplasia to Affect or Not the Optic Nerve in Long-Term Follow-Up of Three Casese91072ENToshihikoMatsuoDepartment of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKiyoshiYamadaDepartment of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMitsuhiroOkanoDepartment of Otorhinolaryngology, School of Medicine, International University of Health and WelfareFibrous dysplasia of the bone is characterized by immature fibrous bones of trabeculae and fibrovascular proliferation in the medulla. In this study, we report three consecutive patients with craniofacial fibrous dysplasia with or without optic nerve involvement. In Case 1, a 43-year-old man with blurred vision in the right eye at the first visit was well until the age of 54 years, when he came back with symptoms suggestive of paranasal sinusitis. Computed tomography scans disclosed a mucocele in the right sphenoid sinus and thickened bilateral ethmoid, sphenoid, and frontal bones. He underwent an emergency nasal endoscopic surgery to make a drainage opening to the sphenoid and ethmoid sinuses on the right side with incomplete success. The pathology of the resected tissue confirmed fibrous dysplasia. With intravenous antibiotics, he recovered from blepharoptosis, complete ophthalmoplegia, and visual acuity decrease on the right side. He was well until the age of 71 years when he had a self-limiting episode of visual field cloudiness caused by the right sphenoid sinus mucocele. At the age of 75 years, he developed abrupt vision loss to no light perception in the right eye. He underwent an open skull surgery to extirpate the sphenoid mucocele on the right side and died of an unknown cause two years later. In Case 2, a 29-year-old man had a two-week-long headache, and computed tomography scans revealed fibrous dysplasia in the bilateral sphenoid bones. Nasal biopsy at the spheno-ethmoid recess proved a pathological diagnosis of fibrous dysplasia. Goldmann perimetry showed normal visual fields in both eyes. He was followed every year by magnetic resonance imaging to maintain normal visual fields until the latest visit at the age of 41 years. In Case 3, a 12-year-old girl was referred to an ophthalmologist to check her vision. She had been diagnosed with fibrous dysplasia of the left maxillary bone at the age of six years by a dentist. She had a gingival resection on the left maxilla at the age of 15 years and had a left maxillary bone resection at 18 years at another hospital. One month after the resection, Goldmann perimetry showed superior peripheral field depression in the left eye, in contrast with the normal visual field in the right eye. She maintained the visual acuity of 1.5 in both eyes until the last visit at the age of 21 years. In fibrous dysplasia as a rare disease, functional and cosmetic problems, including vision problems, should be considered in a case-based approach.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1435-245141012024An effective surgical educational system in the era of robotic surgery: “Double-Surgeon Technique” in robotic gastrectomy for minimally invasive surgery20ENYoshihikoKakiuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhikoKanayaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHajimeKashimaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPurpose Gastric cancer (GC) remains a major malignancy. Robotic gastrectomy (RG) has gained popularity due to various advantages. Despite those advantages, many hospitals lack the necessary equipment for RG and are still performing laparoscopic gastrectomy (LG) due to its established minimal invasiveness and safety.<br>
Methods This study assessed the effectiveness of the “Double-Surgeon Technique” (DST) for improving surgical education and proficiency with LG. The DST involves both a console-side surgeon and a patient-side surgeon working actively in RG, enhancing the skill acquisition needed for LG and potentially reducing surgical time. Assessment of this method was performed by surgical time, and cases were divided into three groups: first half (Phase 1: P1) and second half (P2) before the introduction of DST, and after the introduction of DST (P3).<br>
Results Two surgical trainees were trained using the DST. The learning curve in both reached a plateau in P2, but descended again in P3. For one trainee, surgical time for P3 was significantly reduced compared to P1 (p = 0.001) and P2 (p = 0.0027) despite the intervals between laparoscopic distal gastrectomy as the main surgeon in P3 being significantly longer than in P2 (p = 0.0094). Other surgical results in both trainees did not differ significantly. Further, no difference in induction phase results of RG were evident between surgeons and trainees with or without DST experience.<br>
Conclusion Surgical education using the DST could be effective in the current context of the need for RG and LG.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Coronary cross-sectional area stenosis severity determined using coronary CT highly correlated with coronary functional flow reserve: a pilot study26737ENTakutoKoumotoDivision of Radiation, Okayama Heart ClinicShozoKusachiOkayama University Graduate School of Health SciencesTakumiTomiyaDivision of Cardiovascular Intervention, Okayama Heart ClinicTakuyaAkagiDivision of Cardiovascular Intervention, Okayama Heart ClinicHiroshiKawamuraDivision of Cardiovascular Medicine, Okayama Heart ClinicSatoshiHirohataOkayama University Graduate School of Health SciencesHirosukeYamajiDivision of Cardiovascular Medicine, Okayama Heart ClinicTakashiMurakamiDivision of Cardiovascular Medicine, Okayama Heart ClinicShigeshiKamikawaDivision of Cardiovascular Intervention, Okayama Heart ClinicMasaakiMurakamiDivision of Cardiovascular Intervention, Okayama Heart ClinicFractional flow reserve (FFR) is the gold standard for assessing the physiological significance of coronary stenosis. We examined the potential correlation between digitally measured coronary cross-sectional area stenosis using coronary computed tomography (CT) angiography and FFR. We analyzed data of 32 consecutive patients with stenoses who underwent invasive FFR determination. The cross-sectional area was assessed using 128-slice coronary detector-based spectral CT angiography. Power analysis revealed that the sample size enabled the detection of an area under the receiver operating characteristic (ROC) curve (AUC) of 0.90. FFR ≤ 0.8 and > 0.8 were defined as FFR-positive and FFR-negative, respectively. Intra- and interobserver differences were negligible. Percentage cross-sectional area stenosis was calculated as 100 × (A−B)/A, where A is the cross-sectional area at non-stenotic pre-stenotic segment and B is the cross-sectional area of the most severe stenotic lesion. AUC indicated that percentage cross-sectional area stenosis effectively discriminated between FFR-positive and FFR-negative cases, yielding a sensitivity of 0.882 and specificity of 0.933 at a cutoff of 50% area reduction, with an AUC of 0.976. Lesions with less than 45% cross-sectional area stenosis on coronary CT angiography were not FFR-positive. When ROC analysis was conducted for lesion characteristics, AUC did not significantly improve. In conclusion, the percent coronary cross-sectional area stenosis measured using coronary CT angiography distinguished between FFR-positive and FFR-negative lesions with high accuracy. The severity of coronary cross-sectional area stenosis determined using CT angiography is clinically useful for predicting FFR.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1867-10714382025Overview of task shifting guidelines in Japan: from radiologists to radiological technologists12611268ENAkiKidoDepartment of Radiology, Toyama University HospitalKazukoOhnoDepartment of Radiological Technology, Kyoto University of Medial ScienceKeiYamadaDepartment of Radiology, Kyoto Prefectural University of MedicineKoichiroYamakadoDepartment of Radiology, The Hospital of Hyogo College of MedicineTakaoHirakiDepartment of Radiology, Okayama UniversityTakashiMizowakiDepartment of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto UniversityNorikoAidaDepartment of Diagnostic Radiology, Yokohama City University Graduate School of MedicineNorikoOyama-ManabeDepartment of Radiology, Jichi Medical University Saitama Medical CenterNaokiKodamaDepartment of Radiological Technology, Faculty of Medical Technology, Niigata University of Health and WelfareKatsuhikoUedaDepartment of Radiological Sciences, School of Health Sciences at Narita, International University of Health and WelfareShigekiAokiHealth Data Science, Department of Radiology/Data Science, Graduate School of Medicine, Juntendo UniversityNoriyukiTomiyamaDepartment of Radiology, Osaka University Graduate School of MedicineAs one of the key pillars of work style reform for physicians, task shifting and sharing from radiologists to radiological technologists has been considered. In May 2021, the Radiological Technologists Act was amended, allowing for the expansion of several duties. Alongside these legal and regulatory changes, a notice from Ministry of Health, Labour and Welfare was issued, highlighting tasks to be particularly promoted under the current system prior to the amendment of the Radiological Technologists Act. These amendments authorize radiological technologists to perform advanced and specialized tasks, such as securing venous access for contrast agent administration, which require significantly higher skill levels than their traditional roles. However, the amended legislation did not include specific guidelines, rules, or considerations for the practical implementation of these new duties in daily medical practice, especially from the perspectives of patient safety and quality of care. To address this, the Japan Radiological Society, the Japanese College of Radiology, and the Japan Association of Radiological Technologists collaborated with other related societies to develop guidelines on five key topics:-Guidelines for Safe Conduct of CT/MRI Contrast-Enhanced Examinations: Considering the expanded scope of practice for radiological technologists. -Guidelines for Safe Conduct of Nuclear Medicine Examinations: Aligned with the expanded responsibilities of radiological technologists. -Guidelines for Clinical application of Image-Guided Radiation Therapy (IGRT). -Guidelines for Safe Conduct of Angiography and Interventional Radiology (IR): Adapted for the expanded roles of radiological technologists. -Guidelines for Reporting Findings of STAT Imaging: Addressing urgent conditions with potential impact on life prognosis.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0032-38962025The stress‒strain behavior of poly(methyl acrylate) microparticle-based polymers determined via optical microscopyENYuichiroNishizawaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYutoKawamuraraduate School of Textile Science & Technology, Shinshu UniversityYumaSasakiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityDaisukeSuzukiGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityThe structural integrity of microparticle-based films is maintained through interpenetration of the superficial polymer chains of the microparticles that physically crosslink neighboring microparticles. This structural feature is fundamentally different from those of conventional polymers prepared by solvent casting or bulk polymerization. To understand the mechanical properties of such microparticle-based films, it is necessary to investigate the behavior of their constituent particles. However, methods are still being developed to evaluate microscale structural changes in microparticle-based films during the stretching process leading to film fracture. In this study, we propose a method that combines a stretching stage with optical microscopy to investigate the changes in particle morphology and its positional relationship with surrounding particles during uniaxial tensile tests on microparticle-based films. In a film consisting of cross-linked poly(methyl acrylate) microparticles, the deformation of the particles deviated from affine deformation due to the cross-linked structure. However, the deformation of a group of several (local) particles was confirmed to be location-dependent and larger than that of each particle forming the film. The method established here can be used to contribute to the design of tough microparticle-based films.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1341-96253012024Lymphadenectomy and chemotherapy are effective treatments for patients with 2023 international federation of gynecology and obstetrics stage IIC-high risk endometrial cancer in Japan144156ENYoshinoriTaniDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiroNakamuraDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaeYorimitsuDepartment of Obstetrics and Gynecology, Hiroshima City Hiroshima Citizens HospitalNorikoSekiDepartment of Obstetrics and Gynecology, Japanese Red Cross Society Himeji HospitalMieNakanishiDepartment of Obstetrics and Gynecology, Kagawa Prefectural Central HospitalHironoriItouDepartment of Obstetrics and Gynecology, National Hospital Organization Iwakuni Clinical CenterMiyukiShimizuDepartment of Obstetrics and Gynecology, Kagawa Rosai HospitalDanYamamotoDepartment of Obstetrics and Gynecology, National Organization Fukuyama Medical CenterEtsukoTakaharaDepartment of Obstetrics and Gynecology, Fukuyama City HospitalHisashiMasuyamaDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground In early-stage endometrial cancer (EC), the treatment of aggressive histological subtypes (endometrioid carcinoma grade 3, serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed carcinoma, and carcinosarcoma) is controversial. We aimed to investigate the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage IIC EC according to the 2023 classification.<br>
Methods We retrospectively identified patients with FIGO 2023 stage IC, IIC-intermediate risk (IIC-I), and IIC-high risk (IIC-H) EC who underwent adjuvant therapy or observation after surgery at eight medical institutions from 2004 to 2023. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier estimates and univariate and multivariate analyses.<br>
Results The PFS and OS were significantly worse in patients with FIGO 2023 stage IIC-H EC than in those with FIGO 2023 stage IIC-I EC (PFS: p = 0.008 and OS: p = 0.006). According to the FIGO 2023 stage IIC-H classification, lymphadenectomy and chemotherapy resulted in better prognoses regarding both PFS and OS (p < 0.001 for both) than other treatments. Our findings suggest that lymphadenectomy and chemotherapy effectively reduced vaginal stump and lymph node metastases in FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.008, respectively). Furthermore, in the multivariate analysis, not undergoing lymphadenectomy or chemotherapy were independent predictors of recurrence and poor prognoses in patients with FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.031, respectively).<br>
Conclusion Lymphadenectomy and chemotherapy resulted in better prognoses regarding both recurrence and survival in patients with FIGO 2023 stage IIC high-risk EC.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1438-49572025From sewage sludge to agriculture: governmental initiatives, technologies, and sustainable practices in JapanENThu HuongNguyenGraduate School of Engineering, Kyoto UniversityTakuFujiwaraGraduate School of Engineering, Kyoto UniversityHiromasaYamashitaWater Supply and Sewerage Department, National Institute for Land and Infrastructure ManagementHironoriTogawaWater Supply and Sewerage Department, National Institute for Land and Infrastructure ManagementHaruoMiyakeR & D Department, Japan Sewage Works AgencyMasakoGoto1St Research Department, Japan Institute of Wastewater Engineering and TechnologyHideakiNagareGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityMasatoNakamuraInstitute for Rural Engineering, NAROFumikoOritateInstitute for Rural Engineering, NAROHirotakaIharaInstitute for Agro-Environmental Sciences, NAROMorihiroMaedaGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversitySewage sludge (SS), an underutilized but valuable resource for agriculture, contains essential nutrients, such as phosphorus. In Japan, where dependence on imported fertilizers is high and global price fluctuations persist, using SS as fertilizer presents a sustainable alternative aligned with circular economy goals. This review analyzes Japan’s current efforts to repurpose SS, focusing on technological developments and key policy initiatives that promote safe and effective application. Selective phosphorus recovery technologies mitigate resource depletion, while holistic approaches, such as composting and carbonization, maximize sludge utilization for agricultural applications. Government-led initiatives, including public awareness campaigns, quality assurance standards and research support, have facilitated the adoption of sludge-based fertilizers. To contextualize Japan’s position, international trends, particularly in the EU, are also examined. These comparisons reveal both common strategies and areas for policy and technological advancement, especially regarding regulation of emerging contaminants. By integrating national case studies with global perspectives, the study offers insights into the economic, environmental, and social benefits of SS reuse, contributing to Japan’s goals of resource self-sufficiency and carbon neutrality, while also informing broader sustainable agriculture transitions worldwide.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts30648ENMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHarumiIdeiDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChenWangDepartment of Nursing, School of Life and Health Sciences, HuZhou CollegeYinLiangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYunLiuDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeMatsudaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiKamiokaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIn the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Association between cesarean delivery and childhood allergic diseases in a longitudinal population-based birth cohort from Japan19206ENKeiTamaiDepartment of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNaomiMatsumotoDepartment of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakashiMitsuiDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHisashiMasuyamaDepartment of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakashiYorifujiDepartment of Epidemiology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineThe association between cesarean delivery and childhood allergic diseases, such as atopic dermatitis, food allergy, and bronchial asthma, remains unclear, with limited evidence from Asian populations. We analyzed population-based data of 2,114 children born in Japan in 2010 from the Longitudinal Survey of Babies in the 21st Century, linked to the Perinatal Research Network Database. Comparisons were made between children born by cesarean delivery and those born vaginally. Longitudinal outcomes were atopic dermatitis, food allergy, and bronchial asthma during childhood for each age group up to 9 years of age. We performed Poisson regression analyses with robust variance, and adjusted for child and parent variables, followed by supplementary analyses using generalized estimating equations (GEE). Children born by cesarean delivery did not have a higher risk of most outcomes compared to those born vaginally. GEE analysis found no association between cesarean delivery and atopic dermatitis (adjusted risk ratio [aRR] 0.8, 95% confidence interval [CI] 0.5–1.2), food allergy (aRR 1.1, 95% CI 0.7–1.7), bronchial asthma (aRR 1.0, 95% CI 0.8–1.4), or allergic rhinoconjunctivitis (aRR 0.9, 95% CI 0.8–1.1). This study shows no clear evidence of an association between delivery mode and childhood allergic diseases in Japan.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1068-92653222024Hemodynamic Assessment Using SPY Laser Fluorescence Imaging During Pancreatoduodenectomy with Common Hepatic Artery Resection13341336ENTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotohikoYamadaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYasuoNagaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNoriyukiKanehiraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground. Pancreatectomies combined with arterial resection can be indicated for pancreatic cancer. In a pancreatectomy with arterial resection, intraoperative confirmation of blood flow through reconstructed vessels is crucial. This study highlights the usefulness of SPY laser fluorescence imaging during a pancreatoduodenectomy with common hepatic artery resection (PD-CHAR).<br>
Patient and Methods. A 55-year-old man with borderline resectable pancreatic head cancer underwent a PD-CHAR. After confirming tumor resectability, reconstruction of the CHA to the proper hepatic artery was performed. Subsequently, the superior mesenteric vein was reconstructed.<br>
Results. SPY laser fluorescence imaging demonstrated arterial blood perfusion to the liver through the reconstructed hepatic artery, followed by perfusion from the portal vein. The operation lasted 493 min, with an estimated blood loss of 400 mL. The postoperative course was uneventful with good arterial blood flow.<br>
Conclusion. The SPY Portable Handheld Imager could be valuable for visualizing blood flow in reconstructed vessels and assessing tissue perfusion during a pancreatectomy combined with vascular reconstruction.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1068-926531132024Robot-Assisted Pancreaticoduodenectomy Using the Anterior Superior Mesenteric Artery-First Approach for Pancreatic Cancer87418743ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotohikoYamadaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakeyoshiNishiyamaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYasuoNagaiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNoriyukiKanehiraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground. The superior mesenteric artery (SMA)-first approach for pancreatic cancer (PC) is common surgical technique in pancreaticoduodenectomy. To date, few studies have reported SMA-first approach in robot-assisted pancreaticoduodenectomy (RPD). Herein, we present the anterior SMA-first approach for PC during RPD.<br>
Patient and Method. A 75-year-old man with resectable PC underwent RPD after neoadjuvant chemotherapy. As pancreatic head tumor contacted with the superior mesenteric vein (SMV), the anterior SMA approach was applied. After the mesenteric Kocher maneuver, the jejunum was divided and the left side of the SMA was dissected. Subsequently, the anterior plane of the SMA was dissected. Following the division of branches from the mesenteric vessels, the SMA was taped, and the circumferential dissection around the SMA was performed to detach the pancreatic neck from the SMA completely. Finally, the dissection between the SMV and the tumor was performed under vascular control to remove the specimen.<br>
Conclusions. The anterior SMA-first approach can be optional in patients with PC undergoing RPD. This unique approach allows for the circumferential dissection around the SMA during RPD.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1867-10714322024Evaluation of a novel central venous access port for direct catheter insertion without a peel-away sheath282289ENToshihiroIguchiDepartment of Radiology, Okayama University HospitalTakahiroKawabataDepartment of Radiology, Okayama University HospitalYusukeMatsuiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKojiTomitaDepartment of Radiology, Okayama University HospitalMayuUkaDepartment of Radiology, Okayama University HospitalNoriyukiUmakoshiDepartment of Radiology, Okayama University HospitalSoichiroOkamotoDepartment of Radiology, Okayama University HospitalKazuakiMunetomoDepartment of Radiology, Okayama University HospitalTakaoHirakiDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose This study retrospectively evaluated the feasibility and safety of implanting a newly developed central venous access port (CV-port) that allows catheter insertion into a vein without the use of a peel-away sheath, with a focus on its potential to minimize risks associated with conventional implantation methods.<br>
Materials and methods All procedures were performed using a new device (P-U CelSite Port™ MS; Toray Medical, Tokyo, Japan) under ultrasound guidance. The primary endpoint was the implantation success rate. The secondary endpoints were the safety and risk factors for infection in the early postprocedural period (< 30 days).<br>
Results We assessed 523 CV-port implantations performed in a cumulative total of 523 patients (240 men and 283 women; mean age, 61.6 ± 13.1 years; range, 18–85 years). All implantations were successfully performed using an inner guide tube and over-the-wire technique through 522 internal jugular veins and one subclavian vein. The mean procedural time was 33.2 ± 10.9 min (range 15–112 min). Air embolism, rupture/perforation of the superior vena cava, or hemothorax did not occur during catheter insertion. Eleven (2.1%) intraprocedural complications occurred, including Grade I arrhythmia (n = 8) and subcutaneous bleeding (n = 1), Grade II arrhythmia (n = 1), and Grade IIIa pneumothorax (n = 1). Furthermore, 496 patients were followed up for ≥ 30 days. Six early postprocedural complications were encountered (1.1%), including Grade IIIa infection (n = 4), catheter occlusion (n = 1), and skin necrosis due to subcutaneous leakage of trabectedin (n = 1). These six CV-ports were withdrawn, and no significant risk factors for infection in the early postprocedural period were identified.<br>
Conclusion The implantation of this CV-port device demonstrated comparable success and complication rates to conventional devices, with the added potential benefit of eliminating complications associated with the use of a peel-away sheath.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2041-17231512024Neurotransmitter recognition by human vesicular monoamine transporter 27661ENDohyunImDepartment of Cell Biology, Graduate School of Medicine, Kyoto UniversityMikaJormakkaDepartment of Cell Biology, Graduate School of Medicine, Kyoto UniversityNarinobuJugeDepartment of Genomics and Proteomics, Advanced Science Research Center, Okayama UniversityJun-ichiKishikawaDepartment of Applied Biology, Kyoto Institute of TechnologyTakayukiKatoInstitute for Protein Research, Osaka UniversityYukihikoSugitaLaboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto UniversityTakeshiNodaLaboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto UniversityTomokoUemuraDepartment of Cell Biology, Graduate School of Medicine, Kyoto UniversityYukiShiimuraDepartment of Cell Biology, Graduate School of Medicine, Kyoto UniversityTakaakiMiyajiDepartment of Genomics and Proteomics, Advanced Science Research Center, Okayama UniversityHidetsuguAsadaDepartment of Cell Biology, Graduate School of Medicine, Kyoto UniversitySoIwataDepartment of Cell Biology, Graduate School of Medicine, Kyoto UniversityHuman vesicular monoamine transporter 2 (VMAT2), a member of the SLC18 family, plays a crucial role in regulating neurotransmitters in the brain by facilitating their uptake and storage within vesicles, preparing them for exocytotic release. Because of its central role in neurotransmitter signalling and neuroprotection, VMAT2 is a target for neurodegenerative diseases and movement disorders, with its inhibitor being used as therapeutics. Despite the importance of VMAT2 in pharmacophysiology, the molecular basis of VMAT2-mediated neurotransmitter transport and its inhibition remains unclear. Here we show the cryo-electron microscopy structure of VMAT2 in the substrate-free state, in complex with the neurotransmitter dopamine, and in complex with the inhibitor tetrabenazine. In addition to these structural determinations, monoamine uptake assays, mutational studies, and pKa value predictions were performed to characterize the dynamic changes in VMAT2 structure. These results provide a structural basis for understanding VMAT2-mediated vesicular transport of neurotransmitters and a platform for modulation of current inhibitor design.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0007-09202025Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trialENTadahikoShienOkayama University HospitalFumikataHaraCancer Institute HospitalKenjiroAogiNational Hospital Organization Shikoku Cancer CenterYasuhiroYanagidaShizuoka General HospitalMichikoTsuneizumiGunma Prefectural Cancer CenterNaohitoYamamotoChiba Prefectural Cancer CenterHiroshiMatsumotoSaitama Prefectural Cancer CenterAkihikoSutoNational Cancer Center HospitalKenichiWatanabeHokkaido Cancer CenterMichikoHaraoJichi Medical University HospitalChizukoKanbayashiNiigata Prefectural Cancer CenterMitsuyaItohHiroshima City Hiroshima Citizen’s HospitalTakayukiKadoyaHiroshima University HospitalKeiseiAnanKitakyushu Municipal Medical CenterShigetoMaedaNagasaki Municipal Medical CenterKeitaSasakiNational Cancer Center HospitalGakutoOgawaNational Cancer Center HospitalShigehiraSajiFukushima Medical UniversityHaruhikoFukudaNational Cancer Center HospitalHirojiIwataAichi Cancer Center HospitalBackground: Several prospective studies have evaluated the benefit of primary tumour resection (PTR) in de novo Stage IV breast cancer (BC) patients, but it remains controversial. We aimed to investigate whether PTR improves the survival of de novo stage IV BC patients.<br>
Methods: De novo stage IV BC patients were enrolled in the first registration and received systemic therapies according to clinical subtypes. Patients without progression after primary systemic therapy for 3 months were randomly assigned 1:1 to systemic therapy alone (arm A) or PTR plus systemic therapy (arm B). The primary endpoint was overall survival (OS), and the secondary endpoints included local relapse-free survival (LRFS).<br>
Results: Five hundred seventy patients were enrolled between May 5, 2011, and May 31, 2018. Of these, 407 were randomised to arm A (N = 205) or arm B (N = 202). The median follow-up time of all randomised patients was 60 months. The difference in OS was not statistically significant (HR 0.86 90% CI 0.69–1.07, one-sided p = 0.13). Median OS was 69 months (arm A) and 75 months (arm B). In the subgroup analysis, PTR was associated with improved OS in pre-menopausal patients, or those with single-organ metastasis. LRFS in arm B was significantly longer than that in arm A (median LRFS 20 vs. 63 months: HR 0.42, 95% CI 0.33–0.53, p < 0.0001). There were no treatment-related deaths.<br>
Conclusions: PTR did not prolong OS. However, it improved local control and might benefit a subset of patients, such as those with premenopausal status or with single-organ metastasis. It also improved local relapse-free survival (LRFS), which is a clinically meaningful outcome in trials of systemic therapy.<br>
Clinical trial registration: UMIN Clinical Trials Registry (UMIN000005586); Japan Registry of Clinical Trials (jRCTs031180151).No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1340-68683242025Immediate breast reconstruction surgery for breast cancer: current status and future directions630637ENTadahikoShienDepartment of Breast and Endocrine Surgery, Okayama University HospitalHirokoNogiDepartment of Breast and Endocrine Surgery, The Jikei University School of MedicineAkikoOgiyaDepartment of Breast Surgery, Japanese Red Cross Medical CenterMakotoIshitobiDepartment of Breast Surgery, Mie University School of MedicineChikakoYamauchiDepartment of Radiation Oncology, Shiga General HospitalAyakaShimoDepartment of Breast and Endocrine Surgery, St. Marianna University School of MedicineKazutakaNaruiDepartment of Breast and Thyroid Surgery, Medical Center, Yokohama City UniversityNaomiNaguraDepartment of Breast Surgical Oncology, St Luke’s International HospitalHirohitoSekiDepartment of Breast Surgery, Kyorin University School of MedicineKaoriTerataDepartment of Breast and Endocrine Surgery, Akita University HospitalMihoSaigaDepartment of Plastic Surgery, Okayama University HospitalTatsuyaUchidaDepartment of Plastic Surgery, Okayama University HospitalShinsukeSasadaDepartment of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima UniversityTeruhisaSakuraiSakurai Breast ClinicNaokiNiikuraDepartment of Breast Oncology, Tokai University School of MedicineHirokiMoriDepartment of Plastic and Reconstructive Surgery, Tokyo Medical and Dental UniversityBackground Immediate breast reconstruction (IBR) has become increasingly recognized in Japan as an important component of breast cancer care, improving patients’ quality of life after mastectomy. While the adoption of IBR is growing, the reconstruction rate in Japan remains lower than in Western countries. To clarify the current practice and challenges, the Japanese Breast Cancer Society (JBCS) conducted a nationwide survey.<br>
Methods We conducted a comprehensive web-based questionnaire survey among all JBCS-certified institutions between December 2020 and February 2021. The survey assessed institutional capabilities, surgical techniques, decision-making criteria for BR, and the integration of adjuvant therapy.<br>
Results A total of 429 institutions responded, with 72.5% offering BR and 61.7% capable of providing immediate reconstruction. Nipple-sparing mastectomy (NSM) was performed at 73.7% of institutions offering reconstruction. Multidisciplinary conferences with plastic surgeons were held at 70.5% of institutions. Approximately 30% of institutions discontinued IBR if sentinel lymph node metastases were detected intraoperatively, and 62.8% avoided recommending IBR for patients likely to require postoperative radiation therapy. In 94% of institutions, BR did not cause delays in the administration of adjuvant chemotherapy. However, 15% of institutions modified their radiation therapy approach in reconstructed patients. Additionally, 27% of physicians still believed that BR could negatively affect prognosis.<br>
Conclusions The survey confirmed that IBR is widely performed and feasible in Japan. However, institutional differences, limited access to plastic surgeons, and persistent misconceptions remain significant barriers. Strengthening multidisciplinary collaboration and establishing standardized guidelines will help improve BR rates and patient outcomes in Japan.No potential conflict of interest relevant to this article was reported.