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Kobayashi K, Ayaki M, Nomura T, Nakatani K, Tokumo M, Kokudo Y, Morito T, Ishikawa I, Kondo A, Ando Y, Suto H, Oshima M, Nakabayashi R, Kono T, Fujita N, Yamana H, Kamada H, Ono M, Okano K, Kobara H. Endoscopic findings of gallbladder lesions evaluated with image-enhanced endoscopy: A preliminary study using resected gallbladders. DEN OPEN 2026; 6:e70136. [PMID: 40322542 PMCID: PMC12048906 DOI: 10.1002/deo2.70136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 04/16/2025] [Accepted: 04/20/2025] [Indexed: 05/08/2025]
Abstract
The diagnosis of gallbladder (GB) lesions relies on imaging findings. Transpapillary cholangioscopy can potentially be used to diagnose GB lesions; however, the images obtained remain unclear. This study aimed to characterize the endoscopic findings of GB lesions. We examined the endoscopic features of GB lesions in 50 consecutive patients who underwent cholecystectomy. GB specimens were obtained immediately following cholecystectomy, opened on the side opposite the liver bed, and flushed with saline solution. Each lesion was assessed using a high-resolution endoscope equipped with white light and narrow-band imaging magnification. For elevated lesions, both the surface structure (classified as regular, irregular, or absent) and vascular structure (dilation, meandering, caliber change, non-uniformity, and loose vessel areas) were assessed. Twelve of the 50 patients had elevated lesions, including cholesterol polyp (n = 4), hyperplastic polyp (n = 1), xanthogranulomatous cholecystitis (n = 1), and GB carcinoma (n = 6). Advanced GB carcinoma, as opposed to T1 GB carcinoma, demonstrated a papillary surface with destructive areas and neovascularization on narrow-band imaging magnification. Endoscopic images of each GB lesion were characterized, and the differences between GB carcinomas and benign lesions were identified. This preliminary classification may contribute to innovative imaging diagnosis and targeted biopsy for diagnosing GB lesions under direct vision.
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Affiliation(s)
- Kiyoyuki Kobayashi
- Division of Innovative Medicine for Hepatobiliary and PancreatologyFaculty of MedicineKagawa UniversityKagawaJapan
- Department of Internal MedicineKagawa Rosai HospitalKagawaJapan
- Department of Gastroenterology and HepatologyHITO Medical CenterEhimeJapan
| | - Maki Ayaki
- Department of Gastroenterology and HepatologyHITO Medical CenterEhimeJapan
| | - Takako Nomura
- Department of Gastroenterology and HepatologyHITO Medical CenterEhimeJapan
| | - Kaho Nakatani
- Department of Internal MedicineKagawa Rosai HospitalKagawaJapan
- Department of Gastroenterology and NeurologyFaculty of MedicineKagawa UniversityKagawaJapan
| | - Masaki Tokumo
- Department of Hepato‐Biliary‐Pancreatic SurgeryKagawa Rosai HospitalKagawaJapan
| | - Yasutaka Kokudo
- Department of Hepato‐Biliary‐Pancreatic SurgeryKagawa Rosai HospitalKagawaJapan
| | | | - Ichiro Ishikawa
- Department of NeuropsychiatryFaculty of MedicineKagawa UniversityKagawaJapan
| | - Akihiro Kondo
- Department of Gastroenterological SurgeryFaculty of MedicineKagawa UniversityKagawaJapan
| | - Yasuhisa Ando
- Department of Gastroenterological SurgeryFaculty of MedicineKagawa UniversityKagawaJapan
| | - Hironobu Suto
- Department of Gastroenterological SurgeryFaculty of MedicineKagawa UniversityKagawaJapan
| | - Minoru Oshima
- Department of Gastroenterological SurgeryFaculty of MedicineKagawa UniversityKagawaJapan
| | - Ryota Nakabayashi
- Department of Gastroenterology and NeurologyFaculty of MedicineKagawa UniversityKagawaJapan
| | - Toshiaki Kono
- Department of Gastroenterology and NeurologyFaculty of MedicineKagawa UniversityKagawaJapan
| | - Naoki Fujita
- Department of Gastroenterology and NeurologyFaculty of MedicineKagawa UniversityKagawaJapan
| | - Hiroki Yamana
- Department of Gastroenterology and NeurologyFaculty of MedicineKagawa UniversityKagawaJapan
| | - Hideki Kamada
- Department of Gastroenterology and NeurologyFaculty of MedicineKagawa UniversityKagawaJapan
| | - Masafumi Ono
- Division of Innovative Medicine for Hepatobiliary and PancreatologyFaculty of MedicineKagawa UniversityKagawaJapan
| | - Keiichi Okano
- Department of Gastroenterological SurgeryFaculty of MedicineKagawa UniversityKagawaJapan
| | - Hideki Kobara
- Department of Gastroenterology and NeurologyFaculty of MedicineKagawa UniversityKagawaJapan
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Kyo R, Sasaki T, Yoshida S, Isayama H, Yamada T, Enomoto T, Sumida Y, Kuwai T, Tomita M, Matsuzawa T, Moroi R, Shiratori T, Saida Y. Long-term results of palliative placement of very low-axial force self-expandable metallic stents for malignant colorectal obstruction. DEN OPEN 2026; 6:e70126. [PMID: 40322541 PMCID: PMC12045927 DOI: 10.1002/deo2.70126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 03/13/2025] [Accepted: 04/16/2025] [Indexed: 05/08/2025]
Abstract
Objectives Stent placement is a standard option for palliative decompression in patients with malignant colorectal obstruction. Long-term stent placement is associated with perforation, migration, and stent occlusion. Perforation is associated with life expectancy. Several studies have shown that stents with a high axial force (AF), which is defined as the force required to maintain the stent straight after it has bent, are associated with a higher perforation rate. Therefore, we evaluated the long-term outcomes of using a very low AF stent (Niti-S Enteral Colonic Uncovered stent D-type) for palliative purposes. Methods Eighty-one consecutive patients with malignant colorectal obstruction in 33 medical institutions were evaluated. A stent with very low AF was placed using an endoscope system. We evaluated the adverse events (including perforation, migration, and stent occlusion), 1-year survival rate, and cumulative patency rate. Univariate analysis was conducted using Fisher's exact test. The overall survival and cumulative patency rates were assessed using the Kaplan-Meier method. Results The 1-year cumulative survival rate was 37.8% after stent placement. The 3-month, 6-month, and 1-year cumulative patency rates after stenting were 93.6%, 84.2%, and 75.8%, respectively. The major adverse events included stent migration (6.2%), stent occlusion (9.9%), and perforation (2.5%). Chemotherapy was administered in 26 cases (32.1%) after stenting, and bevacizumab was administered in five cases. However, no cases of perforation occurred following bevacizumab administration. Conclusions Our results suggest that very low AF stents are safe and effective. Therefore, they may be a suitable option for applications, such as palliation. (UMIN 000011304).
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Affiliation(s)
- Rika Kyo
- Department of GastroenterologySaiseikai Yokohamashi‐Nanbu HospitalKanagawaJapan
| | - Takashi Sasaki
- Department of Hepato‐Biliary‐Pancreatic MedicineCancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
| | - Shuntaro Yoshida
- Department of Endoscopy and Endoscopic SurgeryGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Hiroyuki Isayama
- Department of GastroenterologyGraduate School of MedicineJuntendo UniversityTokyoJapan
| | - Tomonori Yamada
- Department of GastroenterologyJapanese Red Cross Aichi Medical Center Nagoya Daini HospitalAichiJapan
| | - Toshiyuki Enomoto
- Department of SurgeryToho University Ohashi Medical CenterTokyoJapan
| | - Yorinobu Sumida
- Department of GastroenterologyNational Hospital OrganizationKyushu Medical Center and Clinical Research CenterFukuokaJapan
| | - Toshio Kuwai
- Department of GastroenterologyNational Hospital Organization Kure Medical Center and Chugoku Cancer CenterHiroshimaJapan
| | | | | | - Rintaro Moroi
- Division of GastroenterologyTohoku University HospitalMiyagiJapan
| | | | - Yoshihisa Saida
- Department of SurgeryToho University Ohashi Medical CenterTokyoJapan
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3
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Miura T, Matsumoto S, Sato A, Kojima S, Sasaki G, Morino M, Matsumoto K, Kashima H, Koito Y, Ishii T, Yoshikawa S, Otake H, Uehara T, Sekine M, Asano T, Miyatani H, Mashima H. Prognostic factors and long-term outcomes with endoscopic submucosal dissection for colorectal tumors in patients aged 75 years or older. DEN OPEN 2026; 6:e70137. [PMID: 40330865 PMCID: PMC12054497 DOI: 10.1002/deo2.70137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/22/2025] [Accepted: 04/25/2025] [Indexed: 05/08/2025]
Abstract
Background Studies regarding the long-term outcomes of endoscopic submucosal dissection (ESD) performed in older patients with colorectal tumors are limited. Therefore, in this study, we aimed to analyze the long-term outcomes of older patients with colorectal tumors who underwent ESD and identify prognostic factors. Methods The data of patients aged ≥ 75 years who underwent ESD for colorectal tumors (adenoma and Tis/T1 colorectal cancer) at a single center were retrospectively analyzed. Prognostic factors for overall survival were analyzed using the Kaplan-Meier method and the Cox proportional hazard model. Results Of the 156 patients included, 51 patients died during the follow-up period, among whom two deaths were due to colorectal cancer. The univariate analysis revealed that an age ≥83 years, Charlson Comorbidity Index ≥2, prognostic nutritional index <46, and neutrophil-to-lymphocyte ratio (NLR) ≥3 were associated with poor overall survival. The multivariate analysis identified Charlson Comorbidity Index ≥2 (hazard ratio: 2.26; 95% confidence interval (CI): 1.24-4.13; p = 0.0008) and NLR ≥3 (hazard ratio, 1.98; 95% CI: 1.02-3.81; p = 0.042) as independent prognostic factors. Conclusions CCI and NLR may be useful parameters for decision-making in older patients undergoing colorectal ESD.
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Affiliation(s)
- Takaya Miura
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Satohiro Matsumoto
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Azumi Sato
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Shu Kojima
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Goya Sasaki
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Mina Morino
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Keita Matsumoto
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Hitomi Kashima
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Yudai Koito
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Takehiro Ishii
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Shuhei Yoshikawa
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Haruka Otake
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Takeshi Uehara
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Masanari Sekine
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Takeharu Asano
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Hiroyuki Miyatani
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
| | - Hirosato Mashima
- Department of GastroenterologyJichi Medical University Saitama Medical CenterSaitamaJapan
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Nagatani T, Wani Y, Takatani M, Fushimi S, Inoue H, Hori S, Kai K, Yamamoto H, Okazaki T, Tanioka M, Okada H, Hirasawa A. Adequacy evaluation of 22-gauge needle endoscopic ultrasound-guided tissue acquisition samples and glass slides preparation for successful comprehensive genomic profiling testing: A single institute experience. DEN OPEN 2026; 6:e70104. [PMID: 40353215 PMCID: PMC12064553 DOI: 10.1002/deo2.70104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 03/12/2025] [Accepted: 03/16/2025] [Indexed: 05/14/2025]
Abstract
Objectives This study aimed to evaluate the successful sequencing rate of Foundation One CDx (F1CDx) using small tissue samples obtained with a 22-gauge needle (22G) through endoscopic ultrasound-guided fine needle acquisition (EUS-TA) and to propose guidelines for tissue quantity evaluation criteria and proper slide preparation in clinical practice. Methods Between June 2019 and April 2024, 119 samples of 22G EUS-TA collected for F1CDx testing at Himeji Red Cross Hospital were retrospectively reviewed. Tissue adequacy was only assessed based on tumor cell percentage (≥20%). The procedure stopped when white tissue fragments reached 20 mm during macroscopic on-site evaluation. The specimens were prepared using both 'tissue preserving sectioning' to retain tissue within formalin-fixed paraffin-embedded blocks and the 'thin sectioning matched needle gauge and tissue length' method with calculation to ensure minimal unstained slides for the 1 mm3 sample volume criterion. Tissue area from HE slides and sample volume were measured, and F1CDx reports were analyzed. Results Of 119 samples, 108 (90.8%) were suitable for F1CDx. Excluding the cases not submitted for testing, in the 45 cases where F1CDx was done using 22G EUS-TA samples, eight (17.8%) had a sum of tissue area tissue of 25 mm2 or greater in the HE-stained sample. However, all cases met the F1CDx 1 mm3 volume criterion by submitting > 30 unstained slides per sample. As a result, 43 of 45 cases (95.6%) were successfully analyzable. Conclusions The 22G EUS-TA needle is an effective tool for providing the sufficient tissue volume required for F1CDx.
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Affiliation(s)
- Tami Nagatani
- Department of PathologyJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
- Department of Genetic MedicineJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
- Clinical Genomic MedicineDentistry and Pharmaceutical ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Yoji Wani
- Department of PathologyJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
| | - Masahiro Takatani
- Department of Internal MedicineJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
| | - Soichiro Fushimi
- Department of PathologyJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
| | - Hirofumi Inoue
- Division of Medical SupportDentistry and Pharmaceutical ScienceOkayama University Graduate School of MedicineOkayamaJapan
| | - Shinichiro Hori
- Department of Internal MedicineJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
| | - Kyohei Kai
- Department of Genetic MedicineJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
| | - Hideki Yamamoto
- Department of Genetic MedicineJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
- Clinical Genomic MedicineDentistry and Pharmaceutical ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Tetsuya Okazaki
- Department of Genetic MedicineJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
- Clinical Genomic MedicineDentistry and Pharmaceutical ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Maki Tanioka
- Clinical Genomic MedicineDentistry and Pharmaceutical ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Hiroyuki Okada
- Department of Internal MedicineJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
| | - Akira Hirasawa
- Department of Genetic MedicineJapanese Red Cross SocietyHimeji Red Cross HospitalHyogoJapan
- Clinical Genomic MedicineDentistry and Pharmaceutical ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
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Okayama Y, Takakuwa T, Shimura Y, Imada K, Kosugi S, Hotta M, Fuchida SI, Tanaka H, Uoshima N, Yoshihara S, Kanda J, Shibayama H, Fukushima K, Ohta K, Yagi H, Ito T, Shimazaki C, Matsumura I, Takaori-Kondo A, Hosen N, Hino M, Kuroda J. Insights into very elderly multiple myeloma treatment from Kansai Myeloma Forum. Hematology 2025; 30:2496545. [PMID: 40296514 DOI: 10.1080/16078454.2025.2496545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 04/16/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND With the aging population, there is a growing need for treating multiple myeloma (MM) in elderly patients; however, real-world studies of them are quite limited. METHODS We retrospectively analyzed 519 patients diagnosed between 1997 and 2020 in the Kansai Myeloma Forum database to evaluate the efficacy and safety of novel agents available for 80 years and older patients with MM. Patients were divided into groups according to the treatment year: up to 2010 (Group 1), 2011-2015 (Group 2), and 2016-2020 (Group 3). RESULTS The median age and number of treatment lines were 83 years (range, 80-96) and 2, respectively. The median time to next treatment (TTNT) was 7.8 months. The TTNT for Group 3 was significantly shorter (3.8 months) than in other groups (p < 0.001). Median progression free survival and overall survival (OS) were 24.4 and 43.7 months, respectively, and did not differ significantly between 3 groups based on pairwise comparisons. In Group 3, the 1-year cumulative incidence of adverse events (AEs), progression or death, and planned treatment leading to treatment discontinuation was 37.7%, 29.4%, and 15.6%, respectively. In addition, the median time until discontinuation due to AEs has been shortened in recent years. CONCLUSION Our findings suggest that AEs threaten the continued treatment of very elderly patients receiving novel agents, with careful management needed to extend the TTNT.
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Affiliation(s)
- Yusuke Okayama
- Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
- Department of Hematology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Teruhito Takakuwa
- Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
- Department of Hematology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
| | - Yuji Shimura
- Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazunori Imada
- Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan
| | - Satoru Kosugi
- Department of Internal Medicine (Hematology), Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Masaaki Hotta
- First Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Shin-Ichi Fuchida
- Department of Hematology, Japan Community Health care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Japan
| | - Hirokazu Tanaka
- Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Nobuhiko Uoshima
- Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Satoshi Yoshihara
- Department of Hematology, Hyogo Medical University Hospital, Nishinomiya, Japan
| | - Junya Kanda
- Department of Hematology and Oncology, Graduate School of MedicineKyoto University, Kyoto, Japan
| | - Hirohiko Shibayama
- Department of Hematology, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Kentaro Fukushima
- Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kensuke Ohta
- Hematology Ohta Clinic, Shinsaibashi, Osaka, Japan
| | - Hideo Yagi
- Department of Hematology and Oncology, Nara Prefecture General Medical Center, Nara, Japan
| | - Tomoki Ito
- First Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Chihiro Shimazaki
- Department of Hematology, Japan Community Health care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Japan
| | - Itaru Matsumura
- Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Akifumi Takaori-Kondo
- Department of Hematology and Oncology, Graduate School of MedicineKyoto University, Kyoto, Japan
| | - Naoki Hosen
- Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Masayuki Hino
- Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Junya Kuroda
- Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Yagyu K, Ueda T, Miyamoto A, Uenishi R, Matsushita H. Previous Moraxella catarrhalis Infection as a Risk Factor of COPD Exacerbations Leading to Hospitalization. COPD 2025; 22:2460808. [PMID: 39963887 DOI: 10.1080/15412555.2025.2460808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 05/10/2025]
Abstract
Haemophilus influenzae (H. influenzae) and Moraxella catarrhalis (M. catarrhalis) are associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, their role in the pathogenesis of COPD is unknown. We retrospectively analysed the clinical data of patients with AECOPD (modified British Medical Research Council scale score, Global Initiative for Chronic Obstructive Lung Disease [GOLD] classification, pre-admission antibiotic and inhalant usage, sputum culture and epidemic influenza virus antigen test) for association with admission frequency. Among 169 eligible patients, pathogens were and were not detected in 64 and 105, respectively. The GOLD classification grade was higher in the non-detection group with a prior antimicrobial administration rate of 21.9% than in the detection group. H. influenzae and M. catarrhalis, each identified in 24.6% of the total number of detected pathogens, were the most common infectious bacteria. The GOLD classification grade was higher in the re-hospitalisation group than in the one-time hospitalisation group (p < 0.01). Regarding type of pathogen, M. catarrhalis infection (n = 16) was more common in the re-hospitalisation group. History of M. catarrhalis, H. influenzae infection and GOLD grade ≥ III were risk factors for re-hospitalisation, with odds ratios of 92.7 (95% confidence interval [CI]: 3.68-2340.0, p < 0.01), 20.1 (CI: 1.48-274.0, p < 0.05) and 9.83 (CI: 2.33-41.4, p < 0.01), respectively. These bacterial infections and severe airway limitation were associated with increased AECOPD frequency. Routine microbial monitoring may be useful for AECOPD prevention, reducing medical burden and improving prognosis.
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Affiliation(s)
- Kyoko Yagyu
- Department of Respiratory Medicine, Osaka City General Hospital, Osaka, Japan
| | - Takahiro Ueda
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Atsushi Miyamoto
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Riki Uenishi
- Department of Respiratory Medicine, Izumi City General Hospital, Izumi, Japan
| | - Haruhiko Matsushita
- Department of Respiratory Medicine, Izumi City General Hospital, Izumi, Japan
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Nakamura K, Okamoto M, Mada T, Harada M, Okumura K, Takamatsu D. Honey-derived Paenibacillus spp. with potential to affect bee brood development in Apis mellifera: Are they a new threat to honey bees? Virulence 2025; 16:2451170. [PMID: 39954288 PMCID: PMC11834430 DOI: 10.1080/21505594.2025.2451170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 12/20/2024] [Accepted: 01/05/2025] [Indexed: 02/17/2025] Open
Abstract
Honey bees are important pollinators in both agriculture and ecosystems, and their health is essential for sustainable human development. Although only two bacteria, Paenibacillus larvae and Melissococcus plutonius, have been identified as bacterial pathogens in honey bee brood for over 100 years, we found three additional Paenibacillus strains (Paenibacillus sp. J27TS7, Paenibacillus azoreducens J34TS1, and Paenibacillus melissococcoides J46TS7) in honey that harmed honey bee brood development. In particular, Paenibacillus sp. J27TS7 was highly virulent in bee larvae (the median lethal dose [LD50] = 12.7 spores/larva) and was comparable to P. larvae (LD50 = 2.3-11.5 spores/larva). Paenibacillus azoreducens J34TS1 showed the second-highest virulence (LD50 = 45.9 spores/larva), and P. melissococcoides J46TS7 was the least virulent (LD50 = 469.0 spores/larva). However, P. melissococcoides was most frequently detected in Japanese honey among the three species, with the highest concentration being 1.8 × 106 spores/mL honey, suggesting its wide distribution in Japanese apiaries. The novel pathogenic Paenibacillus species were categorized into the fast killer (Paenibacillus sp. J27TS7), medium-fast killer (P. melissococcoides), and slow killer (P. azoreducens) like P. larvae strains in terms of the time to kill infected brood; however, histopathological and genome analyses indicated that their pathogenic mechanisms were different from those of P. larvae strains. Moreover, P. melissococcoides showed differences in virulence depending on the lineage of the strain. These findings represent the first discovery of honey bee brood pathogens in more than 100 years and indicate the need to look beyond known pathogens for a comprehensive understanding of honey bee diseases.
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Affiliation(s)
- Keiko Nakamura
- Research and Business Promotion Division, Research Institute for Animal Science in Biochemistry and Toxicology, Sagamihara, Kanagawa, Japan
| | - Mariko Okamoto
- Division of Infectious Animal Disease Research, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan
| | - Takashi Mada
- Division of Infectious Animal Disease Research, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan
| | - Mariko Harada
- Research and Business Promotion Division, Research Institute for Animal Science in Biochemistry and Toxicology, Sagamihara, Kanagawa, Japan
| | - Kayo Okumura
- Research Center for Biosafety, Laboratory Animal and Pathogen Bank, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan
| | - Daisuke Takamatsu
- Division of Infectious Animal Disease Research, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan
- The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan
- Joint Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan
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8
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Tanaka M, Akiyama Y, Mori K, Hosaka I, Endo K, Ogawa T, Sato T, Suzuki T, Yano T, Ohnishi H, Hanawa N, Furuhashi M. Machine learning-based analyses of contributing factors for the development of hypertension: a comparative study. Clin Exp Hypertens 2025; 47:2449613. [PMID: 39773295 DOI: 10.1080/10641963.2025.2449613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 11/25/2024] [Accepted: 12/30/2024] [Indexed: 01/11/2025]
Abstract
OBJECTIVES Sufficient attention has not been given to machine learning (ML) models using longitudinal data for investigating important predictors of new onset of hypertension. We investigated the predictive ability of several ML models for the development of hypertension. METHODS A total of 15 965 Japanese participants (men/women: 9,466/6,499, mean age: 45 years) who received annual health examinations were randomly divided into a training group (70%, n = 11,175) and a test group (30%, n = 4,790). The predictive abilities of 58 candidates including fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, were investigated by statistics analogous to the area under the curve (AUC) in receiver operating characteristic curve analyses using ML models including logistic regression, random forest, naïve Bayes, extreme gradient boosting and artificial neural network. RESULTS During a 10-year period (mean period: 6.1 years), 2,132 subjects (19.1%) in the training group and 917 subjects (19.1%) in the test group had new onset of hypertension. Among the 58 parameters, systolic blood pressure, age and FLI were identified as important candidates by random forest feature selection with 10-fold cross-validation. The AUCs of ML models were 0.765-0.825, and discriminatory capacity was significantly improved in the artificial neural network model compared to that in the logistic regression model. CONCLUSIONS The development of hypertension can be simply and accurately predicted by each ML model using systolic blood pressure, age and FLI as selected features. By building multiple ML models, more practical prediction might be possible.
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Affiliation(s)
- Marenao Tanaka
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Tanaka Medical Clinic, Yoichi, Japan
| | - Yukinori Akiyama
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Japan
| | - Kazuma Mori
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Japan
| | - Itaru Hosaka
- Department of Cardiovascular Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Keisuke Endo
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Toshifumi Ogawa
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tatsuya Sato
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Toru Suzuki
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Natori Toru Internal Medicine and Diabetes Clinic, Natori, Japan
| | - Toshiyuki Yano
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hirofumi Ohnishi
- Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Nagisa Hanawa
- Department of Health Checkup and Promotion, Keijinkai Maruyama Clinic, Sapporo, Japan
| | - Masato Furuhashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
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9
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Hiyama S, Rao RP, Xie F, Takahashi T, Takeshita K, Pandit H. Comparative analysis of posterior tibial slope measurements: Accuracy and reliability of radiographs and CT. J Orthop 2025; 68:62-67. [PMID: 40007522 PMCID: PMC11850100 DOI: 10.1016/j.jor.2025.01.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 01/31/2025] [Indexed: 02/27/2025] Open
Abstract
Introduction This study aimed to evaluate the accuracy and reliability of posterior tibial slope (PTS) measurements obtained from radiographs and CT. PTS, particularly its differences in medial and lateral measurements, plays a crucial role in knee alignment, and inconsistencies in measurement techniques across different imaging modalities have raised concerns about accuracy. Materials and methods This retrospective study included data from 98 Japanese patients legs and 324 Chinese patients legs. PTS was measured on long-leg and short-leg radiographs and CT. Two independent surgeons assessed the measurements, and the inter- and intra-observer reliability were evaluated. The primary outcome was the comparison of medial and lateral PTS measurements, while the secondary aim was to assess the impact of tibial length on measurement accuracy. Discussion The study revealed that lateral PTS was consistently smaller than medial PTS, with an average difference of 1.2°-1.9°. Shorter leg radiographs tend to underestimate PTS compared to full-length tibial measurements. The correlation between measurements from short and long leg radiographs showed that PTS measurements were more prone to errors, which may be due to anatomical factors such as tibial bowing. Inter- and intra-observer reliability were good for medial PTS but poor to moderate for lateral PTS, especially when using radiographs. Conclusion For accurate measurement of both medial and lateral PTS, surgeons should consider using additional examination methods such as CT and MRI. If PTS is to be measured on radiographs, the focus should be on the medial PTS, as it tends to provide more reliable results.
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Affiliation(s)
- Shuhei Hiyama
- Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), University of Leeds, Leeds, UK
- Department of Orthopedics, Jichi Medical University, Shimotsuke, Japan
| | | | - Feng Xie
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | | | | | - Hemant Pandit
- Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), University of Leeds, Leeds, UK
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10
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Hasegawa K, Suzuki K, Murata K, Ogawa Y. Minimum inhibitory concentration of penicillin as a surrogate for in vitro piperacillin susceptibility of ampicillin-susceptible Enterococcus faecalis. Diagn Microbiol Infect Dis 2025; 112:116850. [PMID: 40253875 DOI: 10.1016/j.diagmicrobio.2025.116850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 04/07/2025] [Accepted: 04/13/2025] [Indexed: 04/22/2025]
Abstract
This study evaluated whether penicillin MICs can predict piperacillin susceptibility in Enterococcus faecalis. Among 427 strains, 10 were resistant to piperacillin. Even strains with penicillin MICs of 4-8 µg/mL may exhibit resistance. These findings suggest that even penicillin MICs within the susceptible range may indicate piperacillin resistance, challenging CLSI guidelines.
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Affiliation(s)
- Kohei Hasegawa
- Department of Infectious Diseases, Sakai City Medical Center, Ebaraji 1-1-1, Sakai, Osaka, Japan.
| | - Kumiko Suzuki
- Department of Clinical Laboratory, Sakai City Medical Center, Sakai, Osaka, Japan
| | - Kenya Murata
- Department of Infectious Diseases, Sakai City Medical Center, Ebaraji 1-1-1, Sakai, Osaka, Japan
| | - Yoshihiko Ogawa
- Department of Infectious Diseases, Sakai City Medical Center, Ebaraji 1-1-1, Sakai, Osaka, Japan
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11
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Fukai Y, Hiranaka T, Koide M, Fujishiro T, Okamoto K. Lateral meniscus extrusion on preoperative MRI and its impact upon mid-term clinical outcomes following mobile-bearing unicompartmental knee arthroplasty. J Orthop 2025; 65:15-19. [PMID: 39713556 PMCID: PMC11656092 DOI: 10.1016/j.jor.2024.11.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 11/24/2024] [Accepted: 11/28/2024] [Indexed: 12/24/2024] Open
Abstract
Background The presence of full-thickness cartilage in the lateral compartment on valgus stress radiography is a criterion for medial mobile-bearing unicompartmental knee arthroplasty (UKA). However, the appropriateness of medial UKA is uncertain when preoperative MRI shows extrusion of the lateral meniscus. We therefore assessed how preoperative MRI-detected lateral meniscus extrusion affects mid-term functional outcomes after mobile-bearing UKA. Methods We retrospectively reviewed the records of our patients that underwent mobile-bearing medial UKA between January 2017 and December 2019. Crema's classification system was used to assess MRI of the lateral meniscus, categorizing patients as either grade 0 or ≥ grade 1. We preoperatively evaluated patient-reported outcomes using the Oxford knee score and Knee Society functional score, and then again at the latest follow-up. We also measured range of motion pre- and postoperatively. We compared preoperative individual data with outcome data obtained for at least three years. Results The lateral meniscus extrusion group included 19 knees, and the remainder included 98 knees. Clinical outcomes were similar between these groups (p > 0.05). No progression of lateral arthritis was observed in either group during the follow-up period. Conclusion Excluding UKA as an option for cases with lateral meniscus extrusion findings on preoperative MRI may require reconsideration.
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Affiliation(s)
- Yasuhiro Fukai
- Department of Orthopaedic Surgery and Joint Surgery Centre, Takatsuki, General Hospital, 1-3-13, Kosobe-Cho, Takatsuki, Osaka, 561-1115, Japan
| | - Takafumi Hiranaka
- Department of Orthopaedic Surgery and Joint Surgery Centre, Takatsuki, General Hospital, 1-3-13, Kosobe-Cho, Takatsuki, Osaka, 561-1115, Japan
| | - Motoki Koide
- Department of Orthopaedic Surgery and Joint Surgery Centre, Takatsuki, General Hospital, 1-3-13, Kosobe-Cho, Takatsuki, Osaka, 561-1115, Japan
| | - Takaaki Fujishiro
- Department of Orthopaedic Surgery and Joint Surgery Centre, Takatsuki, General Hospital, 1-3-13, Kosobe-Cho, Takatsuki, Osaka, 561-1115, Japan
| | - Koji Okamoto
- Department of Orthopaedic Surgery and Joint Surgery Centre, Takatsuki, General Hospital, 1-3-13, Kosobe-Cho, Takatsuki, Osaka, 561-1115, Japan
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12
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Tokumitsu K, Sugawara N, Tabuchi T, Yasui-Furukori N. Risk factors for the development of problem gambling in individuals with ADHD symptoms: The mediating roles of gambling engagement and ADHD characteristics. Addict Behav 2025; 166:108327. [PMID: 40101678 DOI: 10.1016/j.addbeh.2025.108327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 02/07/2025] [Accepted: 03/11/2025] [Indexed: 03/20/2025]
Abstract
Gambling disorder is a behavioral addiction characterized by impulsivity and problem gambling, and it often cooccurs with ADHD. This study investigated the associations between ADHD symptoms and problem gambling, focusing on the roles of various forms of gambling engagement. Based on data from the JASTIS 2024 survey, which included 29,268 valid respondents, this cross-sectional study explored how ADHD symptoms are related to the prevalence of problem gambling and specific forms of gambling engagement. Problem gambling was assessed using the Problem Gambling Severity Index, and ADHD symptoms were measured with the Japanese version of the Adult ADHD Self-Report Scale. The results revealed that 22.2 % of the participants with ADHD symptoms exhibited problem gambling, this proportion was significantly higher than that reported in the general population. Causal mediation analysis revealed that all types of gambling engagement, except for lottery, mediated the relationship between ADHD symptoms and problem gambling. Among them, bicycle racing and online casinos exhibited the strongest effects. Multiple regression analysis revealed that online casino use was the strongest predictor of problem gambling both in the general population and among individuals with ADHD symptoms. These findings suggest that individuals with ADHD characteristics increase the risk of engaging in gambling activities, particularly casino and online gambling, which have a high potential for addiction. Given the association between problem gambling and casino-related experiences, this study underscores the need for stringent regulatory measures and targeted prevention strategies, particularly as Japan considers expanding casino operations.
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Affiliation(s)
- Keita Tokumitsu
- Department of Neuropsychiatry, Towada City Hospital, Towada, Aomori, Japan; Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
| | - Norio Sugawara
- Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
| | - Takahiro Tabuchi
- Division of Epidemiology, School of Public Health, Tohoku University Graduate School of Medicine, Japan; Tokyo Foundation for Policy Research, Tokyo, Japan.
| | - Norio Yasui-Furukori
- Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
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Kawata S, Booka E, Honke J, Haneda R, Soneda W, Murakami T, Matsumoto T, Morita Y, Kikuchi H, Hiramatsu Y, Takeuchi H. Relationship of phase angle with postoperative pneumonia and survival prognosis in patients with esophageal cancer: A retrospective cohort study. Nutrition 2025; 135:112743. [PMID: 40203785 DOI: 10.1016/j.nut.2025.112743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 02/17/2025] [Accepted: 03/05/2025] [Indexed: 04/11/2025]
Abstract
OBJECTIVES Phase angle (PhA), derived from bioelectrical impedance analysis (BIA), is an indicator of cell membrane health. Low PhA values reflect poor cellular function and low muscle mass. However, consensus regarding the appropriate cutoff value of PhA remains insufficient, and its impact on outcomes after esophagectomy in patients with esophageal malignancies is not well studied. We aimed to investigate whether preoperative PhA is associated with postoperative complication risk and survival prognosis and whether PhA decrease during the surgical preparation period is a prognostic factor in patients with esophageal cancer. METHODS This retrospective cohort study analyzed data from 194 patients who had undergone esophagectomy for esophageal malignancies. A PhA measured several days before surgery, with cutoff values of 5.0° for men and 4.2° for women, was used. The relationship between postoperative pneumonia and clinicopathological factors and between low PhA and postoperative outcomes and survival prognosis was investigated. The preoperative PhA decline and survival prognosis were analyzed in 134 patients whose PhA was measured twice before surgery. RESULTS Overall, 93 and 101 patients were classified into the low and high PhA groups, respectively. A multivariate analysis showed that a serum albumin level lower than 3.5 g/dL and low PhA were independent risk factors for pneumonia (odds ratio [OR] = 3.40, P = 0.03; OR = 3.42, P = 0.03, respectively). The low PhA group exhibited significantly higher intraoperative fluid balance (6.7 versus 6.0 mL/kg/h, P = 0.01) and a higher proportion of patients who failed to achieve early mobilization on the first postoperative day (46 versus 32%, P = 0.04) than did the high PhA group. Multivariate analysis using a Cox proportional hazards model revealed that low PhA was a poor survival prognostic factor, independent of the clinical stage of esophageal cancer (hazard ratio = 2.61, P < 0.01). In patients whose PhA was measured twice preoperatively, a decrease in PhA during the preoperative period was a significant indicator of poor survival (hazard ratio = 2.59, P < 0.01). The group with a decrease in PhA during the preoperative period had significantly fewer steps than the group with an increase in PhA (6220 ± 2880 versus 8200 ± 2850, P < 0.01). CONCLUSIONS Low PhA was a risk factor for postoperative pneumonia in patients who had undergone esophagectomy and was associated with poor survival prognosis. A decrease in PhA during the preoperative period was a significant poor prognostic factor. Increasing physical activity before surgery may lead to an increase in PhA. Thus, it is important to measure and evaluate PhA changes sequentially in patients with esophageal cancer.
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Affiliation(s)
- Sanshiro Kawata
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Eisuke Booka
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
| | - Junko Honke
- Department of Perioperative Functioning Care and Support, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Ryoma Haneda
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Wataru Soneda
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tomohiro Murakami
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tomohiro Matsumoto
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yoshifumi Morita
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hirotoshi Kikuchi
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yoshihiro Hiramatsu
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan; Department of Perioperative Functioning Care and Support, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
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14
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Matsumoto Y, Otsuka Y, Hosaka H, Kajiwara Y, Okada R, Ito Y, Kimura K, Maeda T, Tsuchiya M, Shimada H. Low prealbumin level is a poor prognostic biomarker for surgically treated pancreatic cancer. Mol Clin Oncol 2025; 23:61. [PMID: 40370692 PMCID: PMC12070150 DOI: 10.3892/mco.2025.2856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 04/07/2025] [Indexed: 05/16/2025] Open
Abstract
The present study aimed to evaluate the clinicopathological and prognostic significance of preoperative prealbumin levels in patients with surgically treated pancreatic cancer. The present retrospective study included 95 patients with pancreatic cancer who underwent radical surgery between January 2011 and December 2021. Of the patients, 49 were male and 46 were female, with a median age of 73 years. According to the median preoperative prealbumin level of 21.1 mg/dl, the patients were divided into low (<21.1 mg/dl) and high (≥21.1 mg/dl) prealbumin groups. Univariate and multivariate analyses were performed to evaluate the prognostic significance of prealbumin levels. Notably, no clinicopathological factors were associated with low prealbumin levels. Overall (P=0.008) and recurrence-free (P=0.004) survival were significantly lower in the low prealbumin group than those in the high prealbumin group. In addition, multivariate analysis showed that low prealbumin levels were an independent risk factor for poor overall (P=0.024) and recurrence-free (P=0.013) survival. Furthermore, the liver (P=0.038) and peritoneal recurrence (P=0.012) rates were higher in the low prealbumin group than those in the high prealbumin group. In conclusion, low preoperative prealbumin levels may be a poor prognostic biomarker in patients with surgically treated pancreatic cancer.
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Affiliation(s)
- Yu Matsumoto
- Department of Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan
| | - Yuichiro Otsuka
- Department of Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan
| | - Hiroka Hosaka
- Department of Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan
| | - Yoji Kajiwara
- Department of Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan
| | - Rei Okada
- Department of Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan
| | - Yuko Ito
- Department of Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan
| | - Kazutaka Kimura
- Department of Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan
| | - Tetsuya Maeda
- Department of Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan
| | - Masaru Tsuchiya
- Department of Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan
| | - Hideaki Shimada
- Department of Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan
- Department of Gastroenterological Surgery and Clinical Oncology, Graduate School of Medicine, Toho University, Tokyo 143-8541, Japan
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15
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Takatsu Y, Harada S, Yamatani Y, Fukuzawa K, Nakamura M, Takano K, Miyati T. Characterization of the evaluation method for hepatobiliary phase image by liver magnetic resonance imaging using Gd-EOB-DTPA. Magn Reson Imaging 2025; 120:110382. [PMID: 40086703 DOI: 10.1016/j.mri.2025.110382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 02/07/2025] [Accepted: 03/05/2025] [Indexed: 03/16/2025]
Abstract
PURPOSE This study aimed to characterize quantitative liver-spleen contrast (Q-LSC) and hepatocellular uptake index (HUI) for evaluating hepatobiliary phase (HBP) images using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) in liver magnetic resonance imaging and to identify differences in the results obtain from these two measurement methods. METHODS Twenty-nine consecutive randomly selected patients were assessed using the 3.0 T MR system. Three regions of interest (ROI) were set for the liver parenchyma and spleen, and signal intensity (SI) was averaged. Q-LSC (SI of the liver divided by the SI of the spleen) and HUI [(Q-LSC-1) × liver volume] were calculated. Moreover, the volume and mean SI of the whole liver and spleen, left lateral segment (LLS), and the other segments were calculated. Subsequently, ROI-based and volume-based values for Q-LSC (R-LSC and V-LSC) and HUI (R-HUI and V-HUI), and the whole and each segment were compared. RESULTS R-LSC and V-LSC for the whole and each segment were not significantly different. Conversely, all combinations of HUI, except between R-HUI and V-HUI were significantly different (P < 0.01), for the whole liver. Correlations between R-LSC, R-HUI, and volume-based LLS were lower than the others. CONCLUSION Q-LSC and HUI were characterized through an imaging evaluation of HBP with Gd-EOB-DTPA. R-LSC and R-HUI, or V-HUI, of the whole liver were strongly correlated, but the LLS affected the data, and HUI depends on liver volume. R-LSC is simple and easy to use for HBP evaluation.
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Affiliation(s)
- Yasuo Takatsu
- Graduate School of Medical Sciences, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan; Department of Molecular Imaging, Clinical Collaboration Unit, School of Medical Sciences, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan; Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan.
| | - Shohei Harada
- Graduate School of Medical Sciences, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan; Department of Radiology, Fujita Health University Hospital, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
| | - Yuya Yamatani
- Central Division of Radiology, Nara Medical University Hospital, 840 Shijo-Cho, Kashihara, Nara 634-8522, Japan.
| | - Kei Fukuzawa
- Department of Radiological Technology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.
| | - Masafumi Nakamura
- Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan; Department of Radiological Technology, Faculty of Health and Welfare, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
| | - Kazuki Takano
- Department of Molecular Imaging, Clinical Collaboration Unit, School of Medical Sciences, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
| | - Tosiaki Miyati
- Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan.
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Nagafuji K, Ito Y, Miyamoto T, Eto T, Kamimura T, Kato K, Miyazaki Y, Wake A, Kohno K, Takase K, Imamura Y, Uchida N, Tanimoto K, Kawano N, Kurokawa T, Kondo Y, Fujisaki T, Tsukada J, Yonemoto K, Akashi K. Clinical Impact of Continuous Dasatinib Administration on the Prognosis of Patients With BCR::ABL1 Acute Lymphoblastic Leukemia: Result of the Prospective MRD2014 Study Conducted by Fukuoka Blood and Marrow Transplantation Group (FBMTG). Eur J Haematol 2025; 114:1001-1010. [PMID: 40052397 DOI: 10.1111/ejh.14407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 02/26/2025] [Accepted: 02/27/2025] [Indexed: 05/07/2025]
Abstract
AIM To assess the efficacy of continuous dasatinib in improving outcomes for adult patients with BCR::ABL1 ALL. METHODS The prospective, multicenter ALL/MRD2014 trial introduced a modified protocol compared to the MRD2008 trial, incorporating continuous dasatinib use and reduced chemotherapy intensity. RESULTS Among the 164 adult ALL patients enrolled (2014-2019), 61 were Philadelphia-positive (Ph+) (median age 50 years; 38 males, 23 females). Post-induction, 96.7% achieved complete remission (CR). The 3-year event-free survival (EFS) and overall survival (OS) were 51% and 76%, respectively. Patients undergoing allo-HSCT in CR1 had improved outcomes, with a 3-year EFS of 64% and OS of 87%. MRD-negative patients before transplantation exhibited superior survival (EFS: 71% vs. 29%; OS: 94% vs. 57%). Comparison with the MRD2008 trial revealed similar outcomes, with the MRD2014 trial achieving a 3-year EFS of 51% and OS of 76% vs. 52% and 84% in MRD2008. Although not statistically significant, the MRD2014 trial showed trends of increased relapse (CIR: 39% vs. 26%, p = 0.305) and reduced non-relapse mortality (NRM: 10% vs. 21%, p = 0.181). CONCLUSION The ALL/MRD2014 trial underscores the importance of MRD status and allo-HSCT in Ph+ ALL. Continuous dasatinib-based regimens offer favorable outcomes in MRD-negative patients. TRIAL REGISTRATION This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR), number UMIN000012382.
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Affiliation(s)
- Koji Nagafuji
- Division of Hematology & Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Yoshikiyo Ito
- Department of Hematology, Imamura General Hospital, Kagoshima, Japan
| | - Toshihiro Miyamoto
- Hematology/Respiratory Medicine, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan
| | - Tetsuya Eto
- Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
| | - Tomohiko Kamimura
- Department of Hematology, HaraSanshin General Hospital, Fukuoka, Japan
| | - Koji Kato
- Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan
| | | | - Atsuhi Wake
- Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Kawasaki, Japan
| | - Kentaro Kohno
- Department of Hematology and Oncology, Japan Community Health Care Organization Kyushu Hospital, Kitakyushu, Japan
| | - Ken Takase
- Department of Hematology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Yutaka Imamura
- Division of Hematology, Our Lady of the Snow Social Medical Corporation St. Mary's Hospital, Kurume, Japan
| | - Naoyuki Uchida
- Department of Hematology, Federation of National Public Service Personnel Mutual aid Associations Toranomon Hospital, Tokyo, Japan
| | - Kazuki Tanimoto
- Department of Hematology and Oncology, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Noriaki Kawano
- Department of Hematology, Miyazaki Prefectural Hospital, Miyazaki, Japan
| | - Toshiro Kurokawa
- Department of Hematology, Toyama Red Cross Hospital, Toyama, Japan
| | - Yukio Kondo
- Department of Hematology, Toyama Prefectural Central Hospital, Toyama, Japan
| | - Tomoaki Fujisaki
- Department of Hematology, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Junichi Tsukada
- Department of Hematology, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Koji Yonemoto
- Division of Biostatistics, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Nishihara, Japan
| | - Koichi Akashi
- Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan
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17
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Yamaguchi Y, Shinno Y, Masuda K, Ariyasu R, Nosaki K, Hakozaki T, Tokito T, Nomura S, Nishio M, Goto K, Hosomi Y, Azuma K, Ohe Y. Efficacy of atezolizumab, bevacizumab, carboplatin, and paclitaxel for epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer after tyrosine kinase inhibitor failure. Curr Probl Cancer 2025; 56:101200. [PMID: 40184872 DOI: 10.1016/j.currproblcancer.2025.101200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 03/17/2025] [Accepted: 03/20/2025] [Indexed: 04/07/2025]
Abstract
BACKGROUND Non-small cell lung cancer (NSCLC) with driver mutations, notably epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase, shows reduced sensitivity to immune checkpoint inhibitors. A subgroup analysis of the IMpower150 data on patients resistant to EGFR tyrosine kinase inhibitors (EGFR-TKI) before enrollment demonstrated prolonged progression-free survival (PFS) with atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) over bevacizumab, carboplatin, and paclitaxel. However, due to the exploratory nature and small sample size, the efficacy of ABCP post-EGFR-TKI failure is still debated. We evaluated ABCP therapy against other platinum-based regimens without immune checkpoint inhibitors in terms of effectiveness and toxicity. METHODS Data from patients with advanced or recurrent NSCLC harboring EGFR-sensitizing mutations treated with platinum-based chemotherapy or ABCP at five Japanese hospitals were retrospectively analyzed. Propensity score matching compared efficacy outcomes, including overall response rate (ORR), PFS, and OS. RESULTS Of 183 EGFR mutation carriers, 33 underwent ABCP therapy, while 150 received platinum-based chemotherapy. Following propensity score matching, 32 and 74 patients were analyzed. In the ABCP group, median PFS and OS were 6.8 and 16.7 months compared to 5.8 and 25.7 months with platinum-based chemotherapy, showing no significant differences in PFS (p = 0.46) and OS (p = 0.85). In liver metastases, ABCP yielded a median PFS of 9.9 versus 6.1 months and an ORR of 62.5 % versus 35.7 % relative to platinum-based chemotherapy, without statistical significance (PFS p = 0.16; ORR p = 0.70). CONCLUSION Compared with platinum-based chemotherapy, ABCP did not improve effectiveness in patients with EGFR-mutated NSCLC after EGFR-TKI failure.
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MESH Headings
- Humans
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Carcinoma, Non-Small-Cell Lung/genetics
- Carcinoma, Non-Small-Cell Lung/pathology
- Carboplatin/administration & dosage
- Carboplatin/pharmacology
- Carboplatin/therapeutic use
- Lung Neoplasms/drug therapy
- Lung Neoplasms/genetics
- Lung Neoplasms/pathology
- Lung Neoplasms/mortality
- Bevacizumab/administration & dosage
- Bevacizumab/pharmacology
- Bevacizumab/therapeutic use
- Female
- Paclitaxel/administration & dosage
- Paclitaxel/pharmacology
- Paclitaxel/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/pharmacology
- Male
- Middle Aged
- Aged
- Retrospective Studies
- ErbB Receptors/genetics
- Mutation
- Antibodies, Monoclonal, Humanized/administration & dosage
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Monoclonal, Humanized/pharmacology
- Protein Kinase Inhibitors/therapeutic use
- Protein Kinase Inhibitors/pharmacology
- Adult
- Aged, 80 and over
- Drug Resistance, Neoplasm
- Tyrosine Kinase Inhibitors
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Affiliation(s)
- Yoh Yamaguchi
- Department of Thoracic Oncology, National Cancer Center Hospital, 104-0045, Japan; Cancer Medicine, Cooperative Graduate School, The Jikei University Graduate School of Medicine, Tokyo, Minato-ku, Tokyo, 105-8461, Japan
| | - Yuki Shinno
- Department of Thoracic Oncology, National Cancer Center Hospital, 104-0045, Japan.
| | - Ken Masuda
- Department of Thoracic Oncology, National Cancer Center Hospital, 104-0045, Japan
| | - Ryo Ariyasu
- Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan
| | - Kaname Nosaki
- Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, 277-8577, Japan
| | - Taiki Hakozaki
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Takaaki Tokito
- Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, 830-0011, Japan
| | - Shogo Nomura
- Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Makoto Nishio
- Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan
| | - Koichi Goto
- Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, 277-8577, Japan
| | - Yukio Hosomi
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Koichi Azuma
- Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, 830-0011, Japan
| | - Yuichiro Ohe
- Department of Thoracic Oncology, National Cancer Center Hospital, 104-0045, Japan; Cancer Medicine, Cooperative Graduate School, The Jikei University Graduate School of Medicine, Tokyo, Minato-ku, Tokyo, 105-8461, Japan
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18
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Hashimoto T, Yahiro T, Khan S, Kimitsuki K, Yoshikawa H, Nishizono A, Komiya K, Hiramatsu K. Assessing the adequacy of blood culture collection in patients aged 80 years or older. J Infect Chemother 2025; 31:102705. [PMID: 40239867 DOI: 10.1016/j.jiac.2025.102705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 03/14/2025] [Accepted: 04/11/2025] [Indexed: 04/18/2025]
Abstract
INTRODUCTION Bloodstream infections (BSIs) are common and fatal conditions in hospitalized patients. Despite higher BSI mortality rates in older adult patients, predicting BSIs in this population remains challenging. This study aimed to assess whether blood culture (BC) collection is adequate for these patients. MATERIALS AND METHODS We conducted a retrospective study of BCs collected from hospitalized patients between June 2020 and March 2024 at a tertiary care hospital in Japan. RESULTS A total of 11,674 BC sets were collected from 5837 hospitalized patients. The true-positive rate was significantly higher in patients aged ≥80 years than in those aged <80 years (13.6 % vs. 10.6 %, p < 0.001). Additionally, the contamination rate was higher in patients aged ≥80 years than in those aged <80 years (3.1 % vs. 2.2 %, p = 0.016). However, chills were less frequent in patients aged ≥80 years. Additionally, the median temperature was lower in older adult patients than in those aged <80 years. CONCLUSIONS BCs may be insufficiently collected in patients aged ≥80 years. Furthermore, a bundled intervention approach is needed for proper BC collection among patients aged ≥80 years.
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Affiliation(s)
| | - Takaaki Yahiro
- Department of Advanced Medical Sciences, Oita University Faculty of Medicine, Japan
| | - Sakirul Khan
- Department of Microbiology, Oita University Faculty of Medicine, Japan; Research Center for Global and Local Infectious Diseases, Japan
| | - Kazunori Kimitsuki
- Department of Microbiology, Oita University Faculty of Medicine, Japan; Research Center for Global and Local Infectious Diseases, Japan
| | - Hiroki Yoshikawa
- Department of Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Japan
| | - Akira Nishizono
- Department of Microbiology, Oita University Faculty of Medicine, Japan; Research Center for Global and Local Infectious Diseases, Japan
| | - Kosaku Komiya
- Department of Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Japan
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Zensho K, Itami K, Matsuda N, Akaike H, Kubota M, Asakawa T, Tokumasu H, Mimaki N. Risk factors for sedation and MRI failure in children with neurodevelopmental disorders undergoing head MRI with oral triclofos sodium and/or rectal chloral hydrate. Brain Dev 2025; 47:104353. [PMID: 40153912 DOI: 10.1016/j.braindev.2025.104353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 03/14/2025] [Accepted: 03/17/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Head magnetic resonance imaging (MRI) is of critical importance in the diagnosis and management of neurodevelopmental disorders. However, the use of sedation in affected children can present a significant challenge. AIMS To identify the factors associated with sedation and MRI failure in children with neurodevelopmental disorders undergoing head MRI with oral triclofos sodium or rectal chloral hydrate. METHODS This retrospective study analyzed 215 MRI sessions of children with neurodevelopmental disorders from January 2020 to December 2021. Sedation was administered via oral triclofos sodium or rectal chloral hydrate. Multivariate logistic regression was used to determine the factors associated with sedation failure and MRI failure. RESULTS The sedation failure rate was 38.1 % (82/215). Factors significantly associated with sedation failure were older age (odds ratio [OR] 1.59, 95 % confidence interval [CI] 1.30-1.95, p < 0.001) and stranger anxiety (OR 4.07, 95 % CI 1.95-8.49, p < 0.001). The age cut-off for increased sedation failure risk was 4.0 years (p < 0.01). The MRI failure rate was 21.9 % (47/215), associated with autism spectrum disorder (ASD) diagnosis (OR 19.00, 95 % CI 2.43-149.00, p < 0.01), stranger anxiety (OR 3.66, 95 % CI 1.62-8.24, p < 0.01), and place anxiety (OR 3.18, 95 % CI 1.33-7.57, p < 0.01). CONCLUSIONS Older age and stranger anxiety are significant risk factors for sedation failure, while ASD diagnosis, stranger anxiety, and place anxiety increase MRI failure risk in children with neurodevelopmental disorders undergoing head MRI.
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Affiliation(s)
- Kazumasa Zensho
- Department of Pediatrics, Kurashiki Medical Center, Okayama 710-8522, Japan; Department of Pediatrics, Okayama University Hospital, Okayama 700-8558, Japan.
| | - Keisuke Itami
- Department of Radiologic Technology, Kurashiki Medical Center, Okayama 710-8522, Japan
| | - Natsuko Matsuda
- Department of Rehabilitation, Kurashiki Medical Center, Okayama 710-8522, Japan
| | - Hiroto Akaike
- Department of Pediatrics, Kurashiki Medical Center, Okayama 710-8522, Japan
| | - Masamichi Kubota
- Department of Pediatrics, Kurashiki Medical Center, Okayama 710-8522, Japan
| | - Toru Asakawa
- Department of Radiology, Kurashiki Medical Center, Okayama 710-8522, Japan
| | - Hironobu Tokumasu
- Department of Clinical Research, Kurashiki Central Hospital, Okayama, Japan
| | - Nobuyoshi Mimaki
- Department of Pediatrics, Kurashiki Medical Center, Okayama 710-8522, Japan; Department of Pediatrics, Okayama University Hospital, Okayama 700-8558, Japan
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20
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Malik MI, Nedadur R, Fox S, Hage A, Hage F, Tzemos N, Chu MWA. Overcoming the Disparity in Mitral Valve Repair: A Sex-Based Analysis of Long-Term Outcomes. Ann Thorac Surg 2025; 119:1278-1285. [PMID: 39209091 DOI: 10.1016/j.athoracsur.2024.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 07/24/2024] [Accepted: 08/06/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Sex disparities remain pervasive across most cardiovascular diseases and continue to demonstrate notably worse early and late outcomes for women, especially after surgical repair. This study aims to investigate outcomes of mitral valve (MV) repair by sex and identify opportunities for improvement. METHODS A single center retrospective analysis of consecutive patients undergoing MV repair from May 2008 to February 2023 was conducted. In-hospital and long-term outcomes, including survival and symptomatic disease recurrence were examined by sex. Adjusted outcome analysis was performed using inverse-probability treatment weighting. RESULTS In total, 490 patients underwent MV repair (median age, 65 years; interquartile range [IQR], 57-73 years; sternotomy n = 128 [26%], minimally invasive n = 362 [74%]), including 343 male and 147 female patients. Median follow-up time was 5.4 years (IQR, 3.1-8.4 years). inverse-probability treatment weighting-adjusted 30-day outcomes for female vs male, including death (1.4% vs 0.6%, P = .59) and major adverse cardiovascular events (8.2% vs 7.6%, P = .81), were not significantly different. Survival for female vs male after mitral valve repair was 94.9% vs 98.0% at 2 years, 91.4% vs 97.8% at 4 years, and 87.2% vs 88.7% at 8 years (hazard ratio, 0.52; IQR, 0.19-1.44). Both unadjusted and inverse-probability treatment weighting-adjusted Cox-regression hazard ratios for survival and freedom from symptomatic disease recurrence demonstrated no significant difference between sexes at long-term follow-up. CONCLUSIONS These contemporary results are encouraging and suggest that a critical "bridging of the gap" between sexes is possible with comprehensive efforts including earlier detection and awareness and improved surgical techniques, though other factors may be important to explore further.
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Affiliation(s)
- Mohsyn Imran Malik
- Division of Cardiac Surgery, Department of Surgery, Western University, London, Ontario, Canada
| | - Rashmi Nedadur
- Division of Cardiac Surgery, Department of Surgery, Western University, London, Ontario, Canada
| | - Stephanie Fox
- Division of Cardiac Surgery, Department of Surgery, Western University, London, Ontario, Canada
| | - Ali Hage
- Division of Cardiac Surgery, Department of Surgery, Western University, London, Ontario, Canada
| | - Fadi Hage
- Division of Cardiac Surgery, Department of Surgery, Western University, London, Ontario, Canada
| | - Nikolaos Tzemos
- Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada
| | - Michael W A Chu
- Division of Cardiac Surgery, Department of Surgery, Western University, London, Ontario, Canada.
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21
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Kawaguchi D, Ito T, Yamamoto Y, Fukaya Y, Mizusawa J, Ochi N, Tomita H, Noritake K. Developmental changes in lower limb joint ranges of motion in Japanese children aged 6-15 years. J Orthop 2025; 64:124-129. [PMID: 39691641 PMCID: PMC11648645 DOI: 10.1016/j.jor.2024.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 07/09/2024] [Indexed: 12/19/2024] Open
Abstract
Background Assessing lower limb ranges of motion (ROMs) is crucial for diagnosing and treating musculoskeletal and neurological disorders in children. Although prior studies examining decline in flexibility among school-age children suggest potential age-related changes in lower limb ROMs, this hypothesis remains unproven. Therefore, in this study, we aim to examine age-related differences in lower limb ROMs among school-age children. Methods The passive ROMs in the lower limbs of 572 typically developing children aged 6-15 years were measured by physiotherapists using goniometers. To examine developmental changes in lower limb ROMs, participants were categorized into four groups: 6-7 years (189 participants), 8-9 years (147 participants), 10-11 years (124 participants), and 12-15 years (112 participants). Results We observed a consistent trend of decreasing ROMs with age across all measures (hip flexion, popliteal angle, knee flexion, knee extension, ankle dorsiflexion, and ankle plantar flexion), excluding hip extension. Notably, only the popliteal angle exhibited values indicating clinically significant sex differences. Conclusions Lower limb ROMs in school-age children generally decrease with age, with notable sex differences observed in the popliteal angle. The lower limb ROM values presented herein can serve as reference values to identify disease- and injury-related changes in lower limb ROMs during this developmental stage.
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Affiliation(s)
- Daisuke Kawaguchi
- Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities, 9-3 Koyaba Kouryuji Cho, Okazaki, 444-0002, Japan
| | - Tadashi Ito
- Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities, 9-3 Koyaba Kouryuji Cho, Okazaki, 444-0002, Japan
| | - Yoshiji Yamamoto
- Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities, 9-3 Koyaba Kouryuji Cho, Okazaki, 444-0002, Japan
| | - Yoshiki Fukaya
- Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities, 9-3 Koyaba Kouryuji Cho, Okazaki, 444-0002, Japan
| | - Jun Mizusawa
- Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities, 9-3 Koyaba Kouryuji Cho, Okazaki, 444-0002, Japan
| | - Nobuhiko Ochi
- Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities, 9-3 Koyaba Kouryuji Cho, Okazaki, 444-0002, Japan
| | - Hidehito Tomita
- Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities, 9-3 Koyaba Kouryuji Cho, Okazaki, 444-0002, Japan
- Toyohashi SOZO University, 20-1 Matsushita, Ushikawa-cho, Toyohashi, 440-8511, Japan
| | - Koji Noritake
- Aichi Prefectural Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities, 9-3 Koyaba Kouryuji Cho, Okazaki, 444-0002, Japan
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22
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Nakano K, Kanenawa K, Isotani A, Morinaga T, Yamamoto K, Miyawaki N, Ko E, Nakamura M, Tanaka Y, Ishizu K, Morofuji T, Hayashi M, Fukunaga M, Hyodo M, Shirai S, Ando K. The efficacy and safety of sodium-glucose cotransporter 2 inhibitors in patients aged over 80 years with heart failure. ESC Heart Fail 2025; 12:2087-2097. [PMID: 39829330 PMCID: PMC12055332 DOI: 10.1002/ehf2.15218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 11/20/2024] [Accepted: 01/02/2025] [Indexed: 01/22/2025] Open
Abstract
AIMS Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) have demonstrated effectiveness in reducing cardiovascular death and heart failure hospitalization (HFH). However, the efficacy and safety of SGLT2 inhibitors in elderly patients with poor general status, such as very low bodyweight or low nutritional status, who are not included in randomized controlled trials, has not yet been examined. In a real-world setting, the introduction of SGLT2 inhibitors to such elderly patients is a very difficult decision to make. We therefore examined the efficacy and safety of these drugs in elderly heart failure patients in a real-world setting. METHODS AND RESULTS In Kokura Memorial Hospital, a retrospective study was conducted on 1559 patients over 80 years old hospitalized for HF between 2018 and 2023. Among them, 1326 were included in the non-SGLT2i group and 233 in the SGLT2i group. A multivariate Cox regression model was used to compare the risk of primary composite outcome (all-cause death and HFH) and secondary safety composite outcome (ischaemic stroke, urinary tract infection and dehydration) at 1 year post-discharge between the two groups. The cumulative 1 year incidence of the composite outcome was significantly higher in the non-SGLT2i group (47.3% vs. 31.6%, P < 0.01). SGLT2 inhibitors independently reduced the risk of all-cause death [adjusted hazard ratio (HR): 0.58, 95% confidence interval (CI): 0.39-0.87, P < 0.01] and HFH (adjusted HR: 0.69, 95% CI: 0.52-0.91, P < 0.01), whereas the risk of safety composite events was not increased (adjusted HR: 0.80, 95% CI: 0.49-1.29, P = 0.36). Subgroup analysis showed no significant interactions between age, diabetes, body mass index, left ventricular ejection fraction, clinical frailty scale, geriatric nutritional risk index and SGLT2 inhibitors consistently reduced composite outcomes across all strata. Similarly, SGLT2 inhibitors did not increase safety composite outcomes at any strata. CONCLUSIONS SGLT2 inhibitors reduce the risk of all-cause death and HFH without increasing adverse events, even in patients over 80 years old. It may be that SGLT2 inhibitors are effective and safe in patients who are basically hesitant to be introduced to SGLT2 inhibitors, such as those with high frailty, low nutritional status or very low bodyweight.
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Affiliation(s)
- Kenji Nakano
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Kenji Kanenawa
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Akihiro Isotani
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | | | - Kaori Yamamoto
- Department of Medical Information Management SectionKokura Memorial HospitalKitakyushuJapan
| | | | - Euihong Ko
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Miho Nakamura
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Yuichi Tanaka
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Kenichi Ishizu
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Toru Morofuji
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Masaomi Hayashi
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Masato Fukunaga
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Makoto Hyodo
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Shinichi Shirai
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
| | - Kenji Ando
- Department of CardiologyKokura Memorial HospitalKitakyushuJapan
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23
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Matsuda A, Ano T, Nakamura Y, Itoi T, Arai K, Kutara K, Sugimoto K, Maeta N. Ozone water has antibacterial properties in dogs without skin barrier impairment. Vet Dermatol 2025; 36:283-290. [PMID: 40084489 DOI: 10.1111/vde.13339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 11/16/2024] [Accepted: 03/05/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND Recently, the use of disinfectants to treat bacterial skin diseases in dogs has garnered attention from the perspective of preventing the spread of antibiotic-resistant bacteria. Ozone water is a disinfectant that combines high antibacterial efficacy and safety; however, there have been no reports verifying its effects on skin barrier function in dogs. OBJECTIVES This study aimed to verify the antibacterial properties and effects of ozone water on skin barrier function in dogs. ANIMALS Four beagles for the antibacterial test and six beagles for the barrier function test. MATERIALS AND METHODS Purified water, 3 mg/L ozone water and 0.005% and 0.05% sodium hypochlorite were used as test products. Skin bacteria were collected 5 min after a single application of each and cultured to measure the bacterial counts. Trans-epidermal water loss (TEWL) and skin surface hydration (SSH) were measured before and after application once a day for 2 weeks. Additionally, the proliferation of canine epidermal keratinocytes (CPEK) was examined after a 5-min incubation with the test products. RESULTS Ozone water and 0.05% sodium hypochlorite significantly reduced the number of skin bacteria. None of the test products worsened TEWL and SSH values. Sodium hypochlorite completely inhibited the proliferation of CPEK, while ozone water did not. CONCLUSIONS AND CLINICAL RELEVANCE Ozone water has an antibacterial effect on canine skin comparable to that of 0.05% sodium hypochlorite, but does not inhibit keratinocyte proliferation in vitro. Thus, ozone water has the potential to be used as a safe and effective disinfectant for canine skin.
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Affiliation(s)
- Akira Matsuda
- Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan
| | | | - Yukari Nakamura
- Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan
| | - Takamasa Itoi
- Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan
| | - Kiyotaka Arai
- Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan
| | - Kenji Kutara
- Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan
| | - Keisuke Sugimoto
- Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan
| | - Noritaka Maeta
- Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan
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24
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Miyake M, Nishimura N, Iemura Y, Yoshikawa M, Torimoto K, Tomioka A, Sakamoto K, Matsumura Y, Naoi M, Ichii D, Inoue K, Narita K, Oyama N, Tomizawa M, Shimizu T, Ohnishi K, Hori S, Morizawa Y, Gotoh D, Nakai Y, Tanaka N, Fujimoto K. Impact of Initial Relative Dose Intensity on Tumor Response and Survival Outcomes in Enfortumab Vedotin Monotherapy for Previously Treated Advanced Urothelial Carcinoma: A Real-world Analysis From a Multicenter Study. Clin Genitourin Cancer 2025; 23:102326. [PMID: 40175211 DOI: 10.1016/j.clgc.2025.102326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/27/2025] [Accepted: 03/04/2025] [Indexed: 04/04/2025]
Abstract
OBJECTIVE To provide real-world evidence regarding the association between the initial relative dose intensity (RDI) of enfortumab vedotin (iRDI-EV) during the first 2 to 3 cycles for locally advanced or metastatic urothelial carcinoma (la/mUC) and patient characteristics, including EV-Ineligible criTeriA (EVITA), tumor response, and survival. METHODS A multicenter database registered 83 patients with locally advanced or metastatic treated with late-line EV monotherapy between 2021 and 2023. The iRDI-EV was calculated based on the dose modification during the first 2 to 3 cycles. A dose of 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle was considered the standard full regimen. Patients were categorized into RDI-1 (lowest), RDI-2, RDI-3, and RDI-full (100% RDI) groups. RESULTS In total, 68 patients were available for iRDI-EV analysis and response evaluation. The overall median iRDI-EV was 87%, with 14, 13, 13, and 28 patients in the 4 groups exhibiting median iRDI-EV of 62%, 73%, 83%, and 100%, respectively. No clear association between the iRDI-EV and objective response was observed. The disease control rate was significantly higher in the RDI-full group (96%) than in the other groups. The patients in higher RDI groups (RDI-3/RDI-full) had longer progression-free survival than the lower RDI groups (RDI-1/RDI-2), with no difference in overall survival. A multiple linear regression analysis revealed higher iRDI-EV was a strong contributor to better response and longer survival. Of the 83 patients, 4 met ≥2 EVITA, exhibiting a higher risk of progression, whereas 79 had EVITA ≤1. CONCLUSIONS Oncologists must continue to learn from real-world data on late-line EV monotherapy for combination therapy.
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Affiliation(s)
- Makito Miyake
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan.
| | | | - Yusuke Iemura
- Department of Urology, Yamatotakada Municipal Hospital, Yamatotakada, Nara, Japan
| | - Motokiyo Yoshikawa
- Department of Urology, Nara Prefecture General Medical Center, Nara, Japan
| | - Kazumasa Torimoto
- Department of Urology, Nara Prefecture General Medical Center, Nara, Japan
| | - Atsushi Tomioka
- Department of Urology, Saiseikai Chuwa Hospital, Sakurai, Nara, Japan
| | - Keichi Sakamoto
- Department of Urology, Osaka Kaisei Hospital, Yodogawa, Osaka, Japan
| | | | - Makito Naoi
- Department of Urology, Okanami General Hospital, Iga, Mie, Japan
| | - Daiki Ichii
- Department of Urology, Tane General Hospital, Osaka, Japan
| | - Kuniaki Inoue
- Department of Urology, Osaka Gyoumeikai Hospital, Osaka, Japan
| | - Kosuke Narita
- Department of Urology, Matsusaka Chuo General Hospital, Matsusaka, Mie, Japan
| | - Nobuo Oyama
- Department of Urology, Nara Prefecture Western Medical Center, Ikoma, Nara, Japan
| | - Mitsuru Tomizawa
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Takuto Shimizu
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Kenta Ohnishi
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Shunta Hori
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Yosuke Morizawa
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Daisuke Gotoh
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Yasushi Nakai
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Nobumichi Tanaka
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan; Department of Prostate Brachytherapy, Nara Medical University, Kashihara, Nara, Japan
| | - Kiyohide Fujimoto
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
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Iwasa N, Kumazawa R, Shimizu M, Okamoto T, Kawabe M, Iwata M, Watanabe K, Kobatake Y, Takashima S, Nishii N. Prognostic value of circulating cardiac and renal biomarkers in dogs with myxomatous mitral valve disease. Res Vet Sci 2025; 189:105649. [PMID: 40215611 DOI: 10.1016/j.rvsc.2025.105649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 03/24/2025] [Accepted: 04/08/2025] [Indexed: 04/25/2025]
Abstract
Prognostic evaluation of canine myxomatous mitral valve disease (MMVD) using circulating biomarkers has been attempted, but comprehensive studies are still limited. The present study aimed to investigate the prognostic value of circulating cardiac and renal biomarkers and imaging data in 37 small-breed dogs with MMVD using retrospective data obtained from 2018 to 2022. The circulating cardiac biomarkers included N-terminal probrain natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), and troponin I. The renal biomarkers included blood urea nitrogen (BUN), creatinine, symmetric dimethylarginine, and cystatin C (Cys-C). The imaging data included vertebral heart score, vertebral left atrial size (VLAS), left-atrial-to-aortic ratio, and left ventricle internal diameter in diastole normalized to bodyweight (LVIDDN) from the medical records. The dogs were categorized into high and low groups based on the cutoff values obtained from the receiver-operating characteristic curves. Kaplan-Meier survival curves were generated, and 1-year MMVD-specific survival rates were compared using the restricted mean survival time (RMST) method. The dogs with high VLAS, LVIDDN, and NT-proBNP, ANP, troponin I, BUN, creatinine, or Cys-C levels had significantly shorter MMVD-specific survival times (p < 0.01). NT-proBNP had the largest RMST difference of 187.0 days (95 % confidence interval [CI]: 104.7-269.3 days), followed by Cys-C with 169.3 days (95 % CI: 98.2-240.5 days). Our study findings highlight the potential of NT-proBNP and Cys-C as key prognostic markers in dogs with MMVD. Incorporating the measurements of blood circulating biomarkers may enhance the accuracy of prognostic prediction in dogs with MMVD.
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Affiliation(s)
- Naoki Iwasa
- Hashima Animal Hospital, 2-17 Asahira, Hashima, Gifu 501-6255, Japan; Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Rie Kumazawa
- Hashima Animal Hospital, 2-17 Asahira, Hashima, Gifu 501-6255, Japan
| | - Mamu Shimizu
- Hashima Animal Hospital, 2-17 Asahira, Hashima, Gifu 501-6255, Japan; Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Tomoko Okamoto
- Hashima Animal Hospital, 2-17 Asahira, Hashima, Gifu 501-6255, Japan
| | - Mifumi Kawabe
- Hashima Animal Hospital, 2-17 Asahira, Hashima, Gifu 501-6255, Japan; Gifu University Animal Medical Center, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Munetaka Iwata
- Hashima Animal Hospital, 2-17 Asahira, Hashima, Gifu 501-6255, Japan; Iwata Veterinary Surgical Service, #901, 4-13-10 Kosuge, Katsushika-ku, Tokyo 124-0001, Japan
| | - Kazuhiro Watanabe
- Hashima Animal Hospital, 2-17 Asahira, Hashima, Gifu 501-6255, Japan; Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Yui Kobatake
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Satoshi Takashima
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Naohito Nishii
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
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26
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Tosaka R, Eguchi T, Ishizuka T, Kawaguchi K, Nagashima T, Nakayama R, Hamada Y. The effects of silk sheets derived from germ-free silkworms on wound healing of full-thickness epithelial defects. Burns 2025; 51:107470. [PMID: 40327970 DOI: 10.1016/j.burns.2025.107470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 02/24/2025] [Accepted: 03/24/2025] [Indexed: 05/08/2025]
Abstract
Collagen is widely used as a scaffold for full-thickness epithelial defects but has poor biostability and often induces hypertrophic scarring. Silk, especially silk derived from germ-free silkworms (SGFS), has high biocompatibility and controllable durability. Therefore, SGFS is possibly for medicine. Herein, we evaluated the effects of SGFS as a scaffold in the wound healing of full-thickness epithelial defects. Epithelial defects were made in the dorsal skin of C57BL/6 J mice, and an SGFS or a collagen sheet was applied to each defect and compared. On days 1, 3, 7, and 14 after surgery, re-epithelialization, inflammatory responses, and granulation tissue formation of each wound were assessed and compared between the groups. Re-epithelialization was observed in the SGFS group on day 3 but no re-epithelialization occurred in the collagen group. Histopathological examination showed less granulation tissue formation in the SGFS group than in the collagen group. IL-6 expression was significantly higher in the SGFS group than in the collagen group on day 1. TGF-β1 expression in the SGFS group was significantly lower than that in the collagen sheet group on days 7 and 14. Based on these results, SGFS promoted re-epithelialization and reduced hypertrophic scarring in the wound healing process compared with collagen.
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Affiliation(s)
- Ryo Tosaka
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
| | - Takanori Eguchi
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
| | - Tadatoshi Ishizuka
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
| | - Koji Kawaguchi
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
| | - Takayuki Nagashima
- Department of Human Animal Relations, Yamazaki University of Animal Health Technology, 4-7-2, Minami-Osawa, Hachioji-shi, Tokyo 192-0364, Japan.
| | - Ryoko Nakayama
- Department of Pathology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
| | - Yoshiki Hamada
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
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27
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Kondo K, Najima Y, Sadato D, Hirama C, Kato K, Sadaga Y, Kato C, Sakai S, Kambara Y, Nabe Y, Teshima K, Asano K, Kurihara K, Shimabukuro M, Jinguji A, Ouchi F, Inai K, Koi S, Shingai N, Haraguchi K, Toya T, Shimizu H, Kobayashi T, Harada H, Okuyama Y, Harada Y, Doki N. Pre-transplant blinatumomab and/or inotuzumab ozogamicin therapy for relapsed/refractory acute lymphoblastic and B/myeloid mixed phenotype acute leukemia in adults. Leuk Res 2025; 153:107704. [PMID: 40306011 DOI: 10.1016/j.leukres.2025.107704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 03/30/2025] [Accepted: 04/23/2025] [Indexed: 05/02/2025]
Abstract
Real-world data on blinatumomab (BLI) and inotuzumab ozogamicin (INO) for relapsed or refractory B-acute lymphoblastic leukemia (RR-ALL) before hematopoietic stem cell transplantation (HCT) are limited. To compare the efficacy of salvage therapy with BLI and/or INO and conventional chemotherapy as a bridge to HCT, we retrospectively evaluated patients with RR-ALL who underwent first HCT at our institute between 2004 and 2023. Based on whether they had received salvage therapy with BLI and/or INO, 70 recipients were divided into a BLI/INO (n = 22) and a control group (n = 48). The complete remission (CR) rate before HCT was higher in the BLI/INO group than in the control group (77.3 % vs. 35.4 %, p = 0.002). Two years after the first HCT, the overall survival (OS) and disease-free survival (DFS) were significantly higher in the BLI/INO group than in the control group (OS, 63.0 % vs. 31.2 %, p = 0.022; DFS 49.6 % vs. 22.9 %, p = 0.049), with comparable cumulative incidence of relapse (CIR, 41.3 % vs. 47.9 %; p = 0.767) and lower tendency of non-relapse mortality (NRM, 9.1 % vs. 29.2 %; p = 0.057). Multivariate analysis revealed that non-CR status before HCT was the only factor associated with poor OS (hazard ratio [HR], 4.263; p < 0.001) and higher CIR (HR, 2.250; p = 0.048). In patients in CR at HCT, there was no difference in HCT outcomes at 2 years (OS, 82.4 % vs. 58.8 %; p = 0.324; DFS, 64.2 % vs. 47.1 %; p = 0.496; CIR, 24.1 % vs. 41.2 %; p = 0.375; NRM, 11.8 % vs. 11.8 %; p = 0.950). BLI and/or INO therapy for RR-ALL was associated with better survival after HCT, probably due to the higher CR rate.
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MESH Headings
- Humans
- Inotuzumab Ozogamicin/administration & dosage
- Inotuzumab Ozogamicin/therapeutic use
- Female
- Male
- Middle Aged
- Antibodies, Bispecific/administration & dosage
- Antibodies, Bispecific/therapeutic use
- Adult
- Retrospective Studies
- Hematopoietic Stem Cell Transplantation
- Young Adult
- Salvage Therapy/methods
- Aged
- Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality
- Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology
- Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
- Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
- Adolescent
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Survival Rate
- Leukemia, Biphenotypic, Acute/pathology
- Leukemia, Biphenotypic, Acute/mortality
- Leukemia, Biphenotypic, Acute/therapy
- Leukemia, Biphenotypic, Acute/drug therapy
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/drug therapy
- Follow-Up Studies
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Affiliation(s)
- Kaori Kondo
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Yuho Najima
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
| | - Daichi Sadato
- Clinical Research Support Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Chizuko Hirama
- Clinical Research Support Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Kana Kato
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Yasutaka Sadaga
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Chika Kato
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Satoshi Sakai
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Yasuhiro Kambara
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Yoshimi Nabe
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Koh Teshima
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Kazuya Asano
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Kazuya Kurihara
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Masashi Shimabukuro
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Atushi Jinguji
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Fumihiko Ouchi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Kazuki Inai
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Satoshi Koi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Naoki Shingai
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Kyoko Haraguchi
- Division of Transfusion and Cell Therapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Takashi Toya
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Hiroaki Shimizu
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Takeshi Kobayashi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Hironori Harada
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan; Laboratory of Oncology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Yoshiki Okuyama
- Division of Transfusion and Cell Therapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Yuka Harada
- Clinical Research Support Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Noriko Doki
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
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28
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Mitsuyoshi T, Tokuda PJ, Kokubo Y, Iwai T, Inoo H, Ashida R, Nasada R, Yamashita M, Tanabe H, Arizono S, Imagumbai T, Kokubo M. Phase 2 Trial of Stereotactic Body Radiation Therapy with Dose Escalation Using Simultaneous Integrated Boost for Spinal Metastases. Adv Radiat Oncol 2025; 10:101760. [PMID: 40342586 PMCID: PMC12059587 DOI: 10.1016/j.adro.2025.101760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 03/03/2025] [Indexed: 05/11/2025] Open
Abstract
Purpose Stereotactic body radiation therapy (SBRT) is an effective treatment approach for spinal metastases. However, local recurrence may occur. This prospective phase 2 trial evaluated whether SBRT with dose escalation in the gross tumor volume through simultaneous integrated boost (SIB-SBRT) can improve local control (LC) without increasing adverse events (AEs). Methods and Materials Eligible patients aged ≥ 20 years with spinal metastases and a life expectancy of > 1 year received SIB-SBRT in 5 fractions over 1 week. The prescribed dose was 30 Gy to the planning target volume for evaluation and an escalated dose of 40 to 45 Gy to the gross tumor volume through SIB. Neurologic examinations and magnetic resonance imaging were performed at 3-, 6-, and 12-month follow-up and every 6 months thereafter. The primary endpoint was the 1-year LC rate. The secondary endpoints included overall survival and AEs, such as vertebral compression fractures (VCFs). Results A total of 25 patients with 28 vertebral segments from September 2020 to March 2023 were enrolled in this study. The median follow-up was 26.2 months, and 24 segments in 21 patients were followed up for >1 year. The 1- and 2-year LC rates were 100.0% and 95.0%, respectively. Local recurrence developed in only 1 patient at 18 months. The 1- and 2-year overall survival rates were 92.0% and 72.8%, respectively. Six patients developed VCFs (3 cases each of grades 1 and 2), with 1- and 2-year cumulative incidence rates of 3.6% and 15.6%, respectively. No radiation myelopathy or other grade ≥ 2 AEs occurred, except for 1 case of grade 2 pain. Conclusions Dose-escalated SIB-SBRT for spinal metastases demonstrates excellent LC with acceptable toxicity, supporting the need for a larger comparative trial.
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Affiliation(s)
- Takamasa Mitsuyoshi
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Peter J. K. Tokuda
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
- Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yumi Kokubo
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Takahiro Iwai
- Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hiroyuki Inoo
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Ryo Ashida
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Ryosuke Nasada
- Department of Radiological Technology, Kobe City Medical Center General Hospital, Kobe, Japan
- Department of Radiological Technology, Kobe City Medical Center West Hospital, Kobe, Japan
| | - Mikiko Yamashita
- Department of Radiological Technology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Hiroaki Tanabe
- Department of Radiological Technology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Shigeki Arizono
- Department of Diagnostic Radiology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Toshiyuki Imagumbai
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
- Department of Radiation Oncology, Medical Research Institute Kitano Hospital, Osaka, Japan
| | - Masaki Kokubo
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
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29
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Yokoshiki H, Watanabe M, Hamaguchi S, Tsutsui H, Shimizu A, Mitsuhashi T, Ishibashi K, Kabutoya T, Yoshiga Y, Kondo Y, Temma T, Takagi M, Tada H. Survival benefit of primary prevention implantable cardioverter-defibrillator/cardiac resynchronization therapy with a defibrillator: Analysis of the Japan cardiac device treatment registry and Japanese cardiac registry of heart failure in cardiology. J Arrhythm 2025; 41:e70084. [PMID: 40357355 PMCID: PMC12067054 DOI: 10.1002/joa3.70084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 04/06/2025] [Accepted: 04/28/2025] [Indexed: 05/15/2025] Open
Abstract
Background Evidence supporting the benefit from primary prevention implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy with a defibrillator (CRT-D) for heart failure with reduced ejection fraction (HFrEF) is scarce in real-world settings. Methods We analyzed propensity score matched cohorts of patients eligible for Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) from Japan cardiac device treatment registry (JCDTR) and Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). The former served as the defibrillator therapy group and the latter as the conventional therapy group. Results During an average follow-up of 24 months, death occurred in 35 of 285 patients (12%) with defibrillator therapy and 65 of 285 patients (23%) with conventional therapy. Adjusted hazard ratios of all-cause death, sudden death, heart failure death, and noncardiac death in defibrillator versus conventional therapy were 0.616 (95% confidence interval [CI]: 0.402-0.943, p = 0.026), 0.274 (95% CI: 0.103-0.731, p = 0.0097), 0.362 (95% CI: 0.172-0.764, p = 0.0077) and 1.45 (95% CI: 0.711-2.949, p = 0.31). After accounting for death without appropriate defibrillator therapy as a competing risk, the cumulative incidence of first appropriate defibrillator therapy in the defibrillator therapy group was nearly identical to that of all-cause death in the conventional therapy group. Subgroup analyses indicated a lack of defibrillator benefit in patients with hypertension (p = 0.01 for interaction). Conclusions Primary prevention ICD/CRT-D reduced the risk of all-cause mortality of patients with HFrEF eligible for SCD-HeFT compared to conventional therapy in the real-world cohort.
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Affiliation(s)
- Hisashi Yokoshiki
- Department of Cardiovascular MedicineSapporo City General HospitalSapporoJapan
| | - Masaya Watanabe
- Department of Cardiovascular MedicineHokko Memorial HospitalSapporoJapan
| | - Sanae Hamaguchi
- Department of Cardiovascular MedicineSapporo City General HospitalSapporoJapan
| | - Hiroyuki Tsutsui
- School of Medicine and Graduate SchoolInternational University of Health and WelfareOtawaraJapan
| | | | - Takeshi Mitsuhashi
- Department of Cardiovascular MedicineHoshi General HospitalKoriyamaJapan
| | - Kohei Ishibashi
- Department of Cardiovascular MedicineNational Cerebral and Cardiovascular CenterSuitaJapan
| | - Tomoyuki Kabutoya
- Division of Cardiovascular Medicine, Department of MedicineJichi Medical University School of MedicineShimotsukeJapan
| | - Yasuhiro Yoshiga
- Division of Cardiology, Department of Medicine and Clinical ScienceYamaguchi University Graduate School of MedicineUbeJapan
| | - Yusuke Kondo
- Department of Cardiovascular MedicineChiba University Graduate School of MedicineChibaJapan
| | - Taro Temma
- Department of Cardiovascular MedicineHokkaido University HospitalSapporoJapan
| | - Masahiko Takagi
- Division of Cardiac ArrhythmiaKansai Medical University Medical CentreMoriguchiJapan
| | - Hiroshi Tada
- Department of Cardiovascular Medicine, Faculty of Medical SciencesUniversity of FukuiFukuiJapan
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30
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Shirakawa K, Mugita M, Hirota M, Izumoto R, Tanaka T, Arai T, Fujioka E, Yabuta H, Yoden T, Sakamoto T, Hiraga K, Watanabe N, Kataoka K, Tsuji S. Association between phase angle and hospital-associated disability in hospitalized patients in the internal medicine ward: A prospective observational study. Clin Nutr ESPEN 2025; 67:296-302. [PMID: 40120939 DOI: 10.1016/j.clnesp.2025.03.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 03/18/2025] [Indexed: 03/25/2025]
Abstract
OBJECTIVE This study aimed to evaluate the association between the phase angle (PhA) and hospital-associated disability (HAD) in older patients admitted to an internal medicine ward. METHODS This was a prospective observational study in a single acute care hospital. HAD was defined as a decrease of at least five points in the Barthel index at discharge compared to pre-admission. Multiple logistic regression analysis was used to determine the association between PhA and HAD. The cut-off point for PhA was evaluated using a receiver operating characteristic curve. RESULTS This study included 215 patients (113 males; mean age: 80.8 years). The HAD incidence rate was 27.9 %. Multiple logistic regression analysis showed that PhA was associated with HAD (odds ratio: 3.47, 95 % confidence interval: 1.95-6.18, p < 0.001). The PhA cut-off points for predicting HAD were 3.7° for men and 3.6° for women. CONCLUSION PhA was associated with HAD in older patients admitted to the internal medicine ward and may be a useful indicator for predicting HAD.
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Affiliation(s)
- Kei Shirakawa
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan.
| | - Moriho Mugita
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Masafumi Hirota
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Ryoji Izumoto
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Takashi Tanaka
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Toshiaki Arai
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Eigo Fujioka
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Hiromu Yabuta
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Tomoki Yoden
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Takuya Sakamoto
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Kenshiro Hiraga
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Noa Watanabe
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Koichiro Kataoka
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan
| | - Shigeyoshi Tsuji
- Department of Rehabilitation, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan; Department of Orthopedic Surgery, Psoriasis Center, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-Ku, Osaka, 550-0006, Japan; Department of Dermatology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
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31
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Naito Y, Inoue S, Tochigi K, Shamoto N, Abe H, Sugihara K, Kondo Y, Kanada Y, Matsui H, Nagayama J, Matsukawa Y, Akamatsu S. Significance of Body Surface Area Correction for Cisplatin Eligibility Based on Renal Function of Patients With Muscle-Invasive Bladder Cancer. Clin Genitourin Cancer 2025; 23:102339. [PMID: 40287317 DOI: 10.1016/j.clgc.2025.102339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 03/20/2025] [Accepted: 03/25/2025] [Indexed: 04/29/2025]
Abstract
INTRODUCTION Creatinine clearance (CCr) ≥60 mL/min without body surface area (BSA) correction is commonly applied to determine the cisplatin (CDDP) eligibility of patients with bladder cancer. However, since CDDP dosages are calculated according to BSA, there is concern that applying renal function without BSA correction may underestimate CDDP eligibility, especially of patients with low BSA. The purpose of this study was to determine whether BSA correction for renal function affects the decision of CDDP eligibility and oncological outcomes. PATIENTS AND METHODS The data of 294 patients who received platinum-based neoadjuvant chemotherapy (NAC) and underwent radical cystectomy for muscle-invasive bladder cancer were retrospectively analyzed. Patients with BSA below and above the median BSA value (1.70 m2) were divided into low-BSA and high-BSA groups. Patients who received ≥20% dose reduction of CDDP or replacement by carboplatin at the first NAC cycle were categorized as "inadequate-CDDP" recipients. "CDDP-eligibility underestimation" was defined as CCr with BSA correction >60 mL/min/1.73 m2 while CCr without BSA correction <60 mL/min. The association of BSA with inadequate-CDDP was evaluated using multivariate analysis. Additionally, differences in clinical outcomes, namely cancer-specific survival (CSS) and objective response rate (ORR) to NAC, between the low- and high-BSA groups were evaluated. RESULTS CDDP-eligibility underestimation was more frequent in the low-BSA group than in the high-BSA group (17% vs. 0%; P < .001). Multivariate analysis revealed that low-BSA was independently associated with the risk of inadequate CDDP (odds ratio, 2.07; P = .012). CSS from initiation of NAC was significantly shorter in the low-BSA group than in the high-BSA group (hazard ratio, 2.24; P = .002). The ORR for NAC was also significantly lower in the low-BSA group (40.8% vs. 57.1%; P = .007). CONCLUSIONS When determining CDDP eligibility for renal function in patients with low BSA, renal function values corrected by standard BSA should be applied to prevent inappropriate dosing reductions.
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Affiliation(s)
- Yushi Naito
- Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Satoshi Inoue
- Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kosuke Tochigi
- Department of Urology, Yokkaichi Municipal Hospital, Yokkaichi, Japan
| | - Noritoshi Shamoto
- Department of Urology, Japan Community Health Care Organization Chukyo Hospital, Nagoya, Japan
| | - Hiroki Abe
- Department of Urology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan
| | | | - Yohei Kondo
- Department of Urology, Narita Memorial Hospital, Toyohashi, Japan
| | - Yoshie Kanada
- Department of Urology, Ichinomiya Municipal Hospital, Ichinomiya, Japan
| | - Hirotaka Matsui
- Department of Urology, Toyohashi Municipal Hospital, Toyohashi, Japan
| | - Jun Nagayama
- Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshihisa Matsukawa
- Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shusuke Akamatsu
- Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Shimomura T, Otsuka N, Urabe F, Muramoto K, Yanagisawa T, Fukuokaya W, Mori K, Tashiro K, Katsumi K, Takahashi H, Yoshihara K, Miyajima K, Imai Y, Iwatani K, Kayano S, Igarashi T, Murakami M, Tsuzuki S, Yamada H, Miki J, Kimura T. PSA Absolute Value Versus PSA Response Rate: Which Is More Valuable for Estimating Survival Outcomes With ARPI Treatment for Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) in Real-World Analyses? Prostate 2025; 85:833-840. [PMID: 40188390 DOI: 10.1002/pros.24885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 02/18/2025] [Accepted: 02/21/2025] [Indexed: 04/08/2025]
Abstract
INTRODUCTION Prostate-specific antigen (PSA) kinetics serve as valuable surrogate markers for estimating survival outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen receptor pathway inhibitors (ARPI). While both the PSA response rate and absolute PSA value are typically assessed, determining which marker holds greater significance in real-world clinical settings is a critical clinical question. In this study, we compare the PSA response rate and absolute PSA value 3 months after the initiation of doublet ARPI therapy to identify which serves as a more effective surrogate marker in practice. PATIENTS AND METHODS A total of 273 patients with mHSPC treated with ARPIs such as abiraterone acetate, enzalutamide, or apalutamide between February 2018 and June 2023 were included in this study. The study investigated PSA kinetics, including PSA levels at 3 months and the PSA response rate at 3 months. The outcome measures assessed were castration-resistant prostate cancer-free survival (CRPCFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS The Youden index for the absolute PSA value at 3 months is 0.740 ng/mL. There is a significant difference in survival outcomes (CRPCFS, CSS, and OS) between patients with PSA levels > 0.740 ng/mL and those with ≤ 0.740 ng/mL. Additionally, the Youden index for the PSA response rate at 3 months is -99.80%. There is also a significant difference in survival outcomes (CRPCFS, CSS, and OS) between patients with response rates > -99.80% and those with rates ≤ -99.80%. In terms of clinical demographics with or without achieving PSA absolute value ≦ 0.740 ng/mL and PSA response rate ≦ -99.8%, although almost factors are different significantly (iPSA, age, PS, LN metastasis, EOD, CHAARTED criteria, LATTITUDE criteria, Hb, ALP, and LDH) between > 0.740 ng/mL and ≦ 0.740 ng/mL cohort, there are no significant difference in clinical factors other than age between > -99.80% and ≦ -99.80% cohort. CONCLUSION Both the absolute value of PSA and the PSA response rate at 3 months after the initiation of ARPI can estimate survival outcomes. However, the PSA response rate is a more valuable surrogate marker for assessing treatment efficacy than the absolute PSA value. This is because the baseline clinical factors differ significantly among cohorts categorized by absolute PSA values, allowing for better predictions of survival outcomes at the start of treatment. Findings of this study could aid in decision-making following the initiation of doublet ARPI therapy within a short timeframe. Further studies are needed to validate our results.
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Affiliation(s)
- Tatsuya Shimomura
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Naoki Otsuka
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Fumihiko Urabe
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Katsuki Muramoto
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Takafumi Yanagisawa
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Wataru Fukuokaya
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Keiichiro Mori
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Kojiro Tashiro
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Kota Katsumi
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Hidetsugu Takahashi
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Kentaro Yoshihara
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Keiichiro Miyajima
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Yu Imai
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Kosuke Iwatani
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Sotaro Kayano
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Taro Igarashi
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Masaya Murakami
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Shunsuke Tsuzuki
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Hiroki Yamada
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Jun Miki
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Takahiro Kimura
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
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Lai A, Liu W, Zhou C, Li Y, Wei S, Liu K, Gong B, Gong X, Liu Y, Zhang G, Zhang J, Gu R, Qiu S, Liu B, Wang Y, Wei H, Mi Y, Wang J. Prognostic impact of co-mutations in adults with IDH1/2-mutated acute myeloid leukemia. BLOOD SCIENCE 2025; 7:e00231. [PMID: 40166375 PMCID: PMC11957625 DOI: 10.1097/bs9.0000000000000231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 02/28/2025] [Indexed: 04/02/2025] Open
Abstract
Acute myeloid leukemia (AML) is characterized by the accumulation of cytogenetic and molecular abnormalities. Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations occur in 11% to 20% of adults with AML. The outcome of IDH1/2-mutated AML is heterogeneous and affected by co-mutational patterns. We retrospectively analyzed 118 patients with IDH1/2-mutated AML who were retrieved from 1597 patients newly diagnosed with AML and treated with intensive chemotherapy. Univariate analysis revealed the NPM1 mutation was a favorable factor (p = 0.019) for overall survival (OS), whereas the DNMT3A mutation was consistently associated with a poor outcome (3-year OS, 52.0%; 3-year relapse-free survival [RFS], 44.8%; and 3-year cumulative incidence of relapse [CIR], 42.6%). Interestingly, the DNMT3A mutation still identified patients with a poorer prognosis, even when measurable residual disease (MRD) was negative after 2 courses of chemotherapy. In a multivariate regression model, age, DNMT3A mutation and MRD positivity were retained as independent adverse markers for OS, RFS, and CIR. In the absence of the DNMT3A or FLT3-ITD mutations, the NPM1 mutation identified patients with a very favorable OS (3-year OS, 96.3% and 86.3%, respectively). Finally, hematopoietic stem cell transplantation in first complete remission significantly improved RFS (p = 0.015) and there was a trend toward improvement in OS (p = 0.282) for patients with the DNMT3A mutation but it did not benefit 2 subgroups with the IDH1/2+/NPM1+/DNMT3A- and IDH1/2+/NPM1+/FLT3-ITD- genotypes. In summary, this study provides a reference for risk stratification and treatment implications for patients with IDH1/2-mutated AML as well as for comparison with results of IDH inhibitor- or venetoclax-based combination therapy.
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Affiliation(s)
- Anli Lai
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Wenbing Liu
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Chunlin Zhou
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Yan Li
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Shuning Wei
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Kaiqi Liu
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Benfa Gong
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Xiaoyuan Gong
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Yuntao Liu
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Guangji Zhang
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Junping Zhang
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Runxia Gu
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Shaowei Qiu
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Bingcheng Liu
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Ying Wang
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Hui Wei
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Yingchang Mi
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Jianxiang Wang
- National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
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Marumo Y, Ri M, Ebina T, Nakamura T, Oshima Y, Nakashima T, Kinoshita S, Suzuki T, Narita T, Sanda T, Komatsu H, Iida S. Prevalence of CCR7-Positive CD8 T Cells as a Prognostic Factor in B-Cell Maturation Antigen -Targeted Chimeric Antigen Receptor T Cell Therapy. EJHAEM 2025; 6:e70040. [PMID: 40330632 PMCID: PMC12051022 DOI: 10.1002/jha2.70040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 03/14/2025] [Accepted: 03/17/2025] [Indexed: 05/08/2025]
Abstract
Background Chimeric antigen receptor T (CAR-T) cell therapy is effective for relapsed or refractory multiple myeloma (RRMM); however, relapse after the B-cell maturation antigen (BCMA) CAR-T cell therapy is associated with poor outcome. Hence, appropriate biomarkers that can predict the outcome are needed. Methods Patients who received idecabtagene vicleucel, a BCMA-targeted CAR-T cell therapy, were divided into two groups according to a cut-off value of 180 days for the progression-free survival (PFS) event. Results Patients in the short responder group were older at diagnosis, had a shorter time from diagnosis to apheresis, and more frequently had prior bispecific antibody treatment or alkylator-containing chemotherapies, while they received less immunomodulatory drugs-based chemotherapy just prior to apheresis. Apheresis samples collected from the long responder group had significantly higher proportion of CD8-positive naïve or stem cell memory (CCR7+CD45RO-) or central memory (CCR7+CD45RO+) T cells. When these two T cell subsets were combined into CCR7-positive CD8 T cells, the patients with high levels of CCR7-positive CD8 T cells showed significantly better PFS. Conclusion In the future, our results will help us to select specific patients that are likely to have a more favorable outcome and should contribute to establishing an optimal application strategy for CAR-T cell therapies in RRMM.
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Affiliation(s)
- Yoshiaki Marumo
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Masaki Ri
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Toru Ebina
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Tomoyuki Nakamura
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Yoshiko Oshima
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Takahiro Nakashima
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Shiori Kinoshita
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Tomotaka Suzuki
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Tomoko Narita
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Takaomi Sanda
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Hirokazu Komatsu
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
| | - Shinsuke Iida
- Department of Hematology and OncologyGraduate School of Medical SciencesNagoya City UniversityNagoyaAichiJapan
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Tominaga A, Wada K, Kato Y, Okazaki K. Romosozumab for managing severe osteoporosis in patients undergoing kidney transplantation: a retrospective case series. JBMR Plus 2025; 9:ziaf049. [PMID: 40353207 PMCID: PMC12063995 DOI: 10.1093/jbmrpl/ziaf049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 03/24/2025] [Accepted: 03/26/2025] [Indexed: 05/14/2025] Open
Abstract
Recipients of kidney grafts often develop severe osteoporosis. However, no consensus has emerged on the most appropriate medications for managing osteoporosis in these recipients. In this study, we investigated the efficacy of romosozumab as an additional treatment option for managing severe osteoporosis in kidney transplant recipients (KTRs). Our retrospective observational study included 12 such recipients who were treated with romosozumab for 12 mo-8 newly initiated on romosozumab and 4 treated with romosozumab after initial treatment with other agents. Endpoints were side effects, new fractures, blood tests, and changes in BMD. Pearson correlation coefficients were used to assess associations of the percent change in bone mineral density after 1 yr of treatment with age, dialysis duration, and time (yr) since transplantation. During treatment with romosozumab, the patients did not develop severe hypocalcemia or experience marked deterioration of kidney function at 1 yr post-treatment. Metabolic markers of bone formation and resorption were similar to those in the general population with osteoporosis. The average changes in BMD at the spine and total hip were 15.18% and 8.83%, respectively, indicating a favorable increase. Further, the change in spine BMD was inversely correlated with age and time since transplantation. Treatment of osteoporosis with romosozumab was observed to be safe for KTRs and had a favorable therapeutic effect on both spine and hip BMD.
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Affiliation(s)
- Ayako Tominaga
- Department of Orthopedic Surgery, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan
| | - Keiji Wada
- Department of Orthopedic Surgery, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan
- Spine Center, Tomei Atsugi Hospital, Atsugi, Kanagawa, 243-8571, Japan
| | | | - Ken Okazaki
- Department of Orthopedic Surgery, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan
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Tsuji T, Onogawa R, Tatsukawa H, Murai A, Hitomi K. Potential activity of chicken amniotic fluid in epidermal development by promoting keratinocyte differentiation. Arch Biochem Biophys 2025; 768:110365. [PMID: 40020982 DOI: 10.1016/j.abb.2025.110365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/07/2025] [Accepted: 02/25/2025] [Indexed: 03/03/2025]
Abstract
Epidermal barrier formation during fetal development, a fundamental biological process in mammals and birds, occurs in the amniotic cavity filled with amniotic fluid (AF). In keratinocytes, indispensable proteins for barrier formation are produced during differentiation, including transglutaminase 1 (TG1) and structural proteins encoded by a gene cluster, epidermal differentiation complex. In general, the chicken fetus rapidly forms a robust epidermal barrier during a relatively short embryonic day (ED); however, little is known about how chicken AF (cAF) contributes to the controls of gene expression of the factors involved in epidermal development. Here, we first demonstrated that the cross-linking activity of TG1 gradually increased, followed by the development of barrier function until ED18 in the chicken fetal epidermis. Then, we revealed that cAF harvested at specific fetal stages had the ability to enhance the expression and activity of TG1, and to facilitate the expression of genes for the other epidermal transglutaminases, structural proteins, and differentiation-related transcription factors in human cultured keratinocytes. Furthermore, the thermal denaturation of cAF components reduced cAF efficacy in promoting the expression of those factors. The fractionated proteinaceous solution of cAF possessed the activity to induce the protein expression of barrier formation-related factors, such as the transcription factor zinc finger protein 750. These results indicated that proteinaceous molecules in cAF have the potential to activate the gene expression networks involved in epidermal barrier formation. This finding will provide novel insights into the physiological role of AF in fetal epidermal development.
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Affiliation(s)
- Tokuji Tsuji
- Laboratory of Cellular Biochemistry, Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, 464-8601, Japan.
| | - Ryo Onogawa
- Laboratory of Cellular Biochemistry, Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, 464-8601, Japan
| | - Hideki Tatsukawa
- Laboratory of Cellular Biochemistry, Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, 464-8601, Japan
| | - Atsushi Murai
- Laboratory of Animal Nutrition, Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan
| | - Kiyotaka Hitomi
- Laboratory of Cellular Biochemistry, Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, 464-8601, Japan
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Mizushima A, Mitsuboshi S, Kobayashi S, Hara K, Ara Y, Agatsuma T. Evaluation of antibiotic de-escalation based on the DASON criteria by pharmacist-led post-prescription review and feedback: A retrospective study in a medium-sized Japanese hospital. J Infect Chemother 2025; 31:102716. [PMID: 40268193 DOI: 10.1016/j.jiac.2025.102716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 03/19/2025] [Accepted: 04/20/2025] [Indexed: 04/25/2025]
Abstract
INTRODUCTION Among antimicrobial stewardship team (AST) activities, de-escalation, which is aimed at optimizing antibiotic use, lacks a standardized evaluation method. The Duke Antimicrobial Stewardship Outreach Network (DASON) criteria provide a framework for assessing de-escalation; however, their applicability in small to medium-sized hospitals in Japan has remained unclear. We aimed to evaluate the effectiveness of AST pharmacist-led post-prescription review and feedback (PPRF) using multiple indicators, including de-escalation based on the DASON criteria, to determine whether these indicators are also applicable in medium-sized hospitals. METHODS A retrospective study was conducted at a 330-bed hospital, comparing pre-PPRF (April 2021 to March 2022) and post-PPRF (April 2022 to March 2023) periods. The effectiveness of AST pharmacist-led PPRF was evaluated using the de-escalation rate determined by the DASON criteria, inappropriate antibiotic use in definitive therapy, days of therapy (DOT), and days of antibiotic spectrum coverage (DASC) per DOT. RESULTS The de-escalation rate significantly increased from 20 % to 45 % (P < 0.01), and inappropriate antibiotic use in definitive therapy decreased from 7 % to 0 % after AST pharmacist-led PPRF. While DOT significantly increased from 11 days to 13 days (P = 0.02), no significant change was observed in the DASC/DOT ratio. CONCLUSION This study suggests that de-escalation based on the DASON criteria can be an effective quantitative indicator for evaluating AST pharmacist-led PPRF in medium-sized hospitals. The findings also suggest that incorporating multiple indicators tailored to each hospital's conditions can provide a more comprehensive framework for evaluating AST pharmacist-led PPRF.
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Affiliation(s)
- Atsuhiro Mizushima
- Department of Pharmacy, National Hospital Organization Yokohama Medical Center, Kanagawa, Japan.
| | | | - Seiya Kobayashi
- Department of Planning, National Hospital Organization Shinshu Ueda Medical Center, Nagano, Japan
| | - Kaori Hara
- Department of Nursing, National Hospital Organization Shinshu Ueda Medical Center, Nagano, Japan
| | - Yoshiaki Ara
- Department of Pharmacy, National Hospital Organization Disaster Medical Center, Tokyo, Japan
| | - Toshihiko Agatsuma
- Department of Respiratory Medicine, National Hospital Organization Shinshu Ueda Medical Center, Nagano, Japan
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Kobayashi N, Nakaura T, Yoshida N, Nagayama Y, Kidoh M, Uetani H, Sakabe D, Kawamata Y, Funama Y, Tsutsumi T, Hirai T. Impact of deep learning reconstruction on radiation dose reduction and cancer risk in CT examinations: a real-world clinical analysis. Eur Radiol 2025; 35:3499-3507. [PMID: 39613960 DOI: 10.1007/s00330-024-11212-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 09/26/2024] [Accepted: 10/14/2024] [Indexed: 12/01/2024]
Abstract
PURPOSE The purpose of this study is to estimate the extent to which the implementation of deep learning reconstruction (DLR) may reduce the risk of radiation-induced cancer from CT examinations, utilizing real-world clinical data. METHODS We retrospectively analyzed scan data of adult patients who underwent body CT during two periods relative to DLR implementation at our facility: a 12-month pre-DLR phase (n = 5553) using hybrid iterative reconstruction and a 12-month post-DLR phase (n = 5494) with routine CT reconstruction transitioning to DLR. To ensure comparability between two groups, we employed propensity score matching 1:1 based on age, sex, and body mass index. Dose data were collected to estimate organ-specific equivalent doses and total effective doses. We assessed the average dose reduction post-DLR implementation and estimated the Lifetime Attributable Risk (LAR) for cancer per CT exam pre- and post-DLR implementation. The number of radiation-induced cancers before and after the implementation of DLR was also estimated. RESULTS After propensity score matching, 5247 cases from each group were included in the final analysis. Post-DLR, the total effective body CT dose significantly decreased to 15.5 ± 10.3 mSv from 28.1 ± 14.0 mSv pre-DLR (p < 0.001), a 45% reduction. This dose reduction significantly lowered the radiation-induced cancer risk, especially among younger women, with the estimated annual cancer incidence from 0.247% pre-DLR to 0.130% post-DLR. CONCLUSION The implementation of DLR has the possibility to reduce radiation dose by 45% and the risk of radiation-induced cancer from 0.247 to 0.130% as compared with the iterative reconstruction. KEY POINTS Question Can implementing deep learning reconstruction (DLR) in routine CT scans significantly reduce radiation dose and the risk of radiation-induced cancer compared to hybrid iterative reconstruction? Findings DLR reduced the total effective body CT dose by 45% (from 28.1 ± 14.0 mSv to 15.5 ± 10.3 mSv) and decreased estimated cancer incidence from 0.247 to 0.130%. Clinical relevance Adopting DLR in clinical practice substantially lowers radiation exposure and cancer risk from CT exams, enhancing patient safety, especially for younger women, and underscores the importance of advanced imaging techniques.
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Affiliation(s)
- Naoki Kobayashi
- Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan
| | - Takeshi Nakaura
- Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan.
| | - Naofumi Yoshida
- Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan
| | - Yasunori Nagayama
- Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan
| | - Masafumi Kidoh
- Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan
| | - Hiroyuki Uetani
- Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan
| | - Daisuke Sakabe
- Department of Central Radiology, Kumamoto University Hospital, Kumamoto, Japan
| | - Yuki Kawamata
- Department of Central Radiology, Kumamoto University Hospital, Kumamoto, Japan
| | - Yoshinori Funama
- Department of Medical Physics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan
| | - Takashi Tsutsumi
- Disease Applied Research Department, Research and Development Center, Canon Medical Systems, Otawara, Japan
| | - Toshinori Hirai
- Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan
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Oikawa Y, Umakoshi M, Suzuki K, Kudo-Asabe Y, Miyabe K, Koyama K, Yoshida M, Tanaka M, Nanjo H, Fukuda M, Yamada T, Goto A. Prognostic significance of cancer-associated fibroblasts and tumor-associated macrophages in the tongue squamous cell carcinoma and their correlation with tumor budding. Oral Oncol 2025; 165:107295. [PMID: 40327897 DOI: 10.1016/j.oraloncology.2025.107295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 03/26/2025] [Accepted: 04/05/2025] [Indexed: 05/08/2025]
Abstract
BACKGROUND Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the oral cavity and is characterized by a high propensity for invasion and a poor prognosis. Recent studies have highlighted the critical roles of cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) in tumor progression, particularly within the tumor microenvironment (TME). OBJECTIVE This study aimed to investigate the correlation between CAFs, TAMs, and tumor budding in tongue squamous cell carcinoma (TSCC), and evaluate their impact on prognostic factors. METHODS A total of 88 cases of surgically resected TSCC were analyzed. Immunohistochemical staining was performed using markers of CAFs (fibroblast activation protein, FAP) and TAMs (CD163). The correlation between CAF and TAM scores, tumor budding, and various clinicopathological factors was assessed. TAM scores were evaluated for the number of TAMs in the intratumoral areas (TAM-t) and the invasive front (TAM-fr). CAF scores were evaluated for cancer cells in the intratumoral area (cCAF-t), stromal cells in the intratumoral area (sCAF-t), stromal cells in the invasive front (sCAF-fr), and the infiltration pattern of CAF (IPC). RESULTS The IPC score was significantly associated with the tumor budding scores (p < 0.001) and poor DFS (p < 0.01). In the multivariate analysis, cCAF-t, sCAF-t, and IPC scores emerged as independent prognostic factors (p < 0.05) for early-stage TSCC. CAFs may play a pivotal role in tumor invasion. CONCLUSION These findings indicate that CAFs significantly influence the invasive characteristics of TSCC and are correlated with tumor budding and a poor prognosis. These results underscore the potential of targeting CAFs as a therapeutic strategy for improving OSCC outcome.
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Affiliation(s)
- Yuki Oikawa
- Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan; Department of Dentistry and Oral Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Michinobu Umakoshi
- Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan; Department of Pathology, Akita City Hospital, Akita, Japan.
| | - Kenichiro Suzuki
- Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan; Department of Dentistry and Oral Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Yukitsugu Kudo-Asabe
- Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan
| | - Ken Miyabe
- Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan
| | - Kei Koyama
- Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan
| | - Makoto Yoshida
- Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan
| | - Masamitsu Tanaka
- Department of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine, Akita, Japan
| | - Hiroshi Nanjo
- Department of Pathology, Akita University Hospital, Akita, Japan
| | - Masayuki Fukuda
- Department of Dentistry and Oral Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Takechiyo Yamada
- Department of Otorhinolaryngology, Head and Neck Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Akiteru Goto
- Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan
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Tsujimae M, Saito T, Sakai A, Takenaka M, Omoto S, Hamada T, Ota S, Shiomi H, Takahashi S, Fujisawa T, Suda K, Matsubara S, Uemura S, Iwashita T, Yoshida K, Maruta A, Okuno M, Iwata K, Hayashi N, Mukai T, Yasuda I, Isayama H, Nakai Y, Masuda A. Necrosectomy and its timing in relation to clinical outcomes of EUS-guided treatment of walled-off pancreatic necrosis: a multicenter study. Gastrointest Endosc 2025; 101:1174.e1-1174.e20. [PMID: 39603541 DOI: 10.1016/j.gie.2024.11.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 10/29/2024] [Accepted: 11/18/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND AND AIMS EUS-guided transmural drainage with on-demand endoscopic necrosectomy (EN) is increasingly used to manage walled-off necrosis (WON). It has not been fully elucidated how EN and its timing are correlated with treatment outcomes compared with the drainage-based approach. METHODS Within a multi-institutional cohort of 423 patients with pancreatic fluid collections, including 227 patients with WON, 153 patients were identified who received the step-up treatment after the initial EUS-guided drainage of symptomatic WON; this included 102 EN patients and 51 non-EN (drainage) patients. Using the competing-risks multivariable proportional hazards regression model with adjustment for potential confounders, we calculated subdistribution hazard ratios (SHRs) for clinical treatment success (WON resolution) according to use of EN and its timing. RESULTS Compared with drainage alone, the EN-based treatment was associated with a shorter time to clinical success with a multivariable SHR of 1.66 (95% confidence interval, 1.12-2.46). Despite a higher risk of procedure-related bleeding in the EN group, there were no differences in the rates of severe adverse events (7.8% vs 5.9% in the EN and non-EN groups, respectively) or mortality (6.9% vs 9.8%). In the EN-treated patients, the timing of EN was not statistically significantly associated with the time to clinical success (Ptrend = .34). CONCLUSIONS Among patients receiving EUS-guided treatment of symptomatic WON, the use of EN in addition to drainage procedures was associated with earlier disease resolution. Further research is desired to determine the optimal timing of initiating EN considering a risk-benefit balance and cost-effectiveness.
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Affiliation(s)
- Masahiro Tsujimae
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Tomotaka Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Arata Sakai
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Mamoru Takenaka
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Shunsuke Omoto
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shogo Ota
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan; Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University, Hyogo, Japan
| | - Hideyuki Shiomi
- Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University, Hyogo, Japan
| | - Sho Takahashi
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Toshio Fujisawa
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Kentaro Suda
- Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Saburo Matsubara
- Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Shinya Uemura
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Takuji Iwashita
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Kensaku Yoshida
- Department of Gastroenterology, Gifu Prefectural General Medical Center, Gifu, Japan
| | - Akinori Maruta
- Department of Gastroenterology, Gifu Prefectural General Medical Center, Gifu, Japan
| | - Mitsuru Okuno
- Department of Gastroenterology, Gifu Municipal Hospital, Gifu, Japan
| | - Keisuke Iwata
- Department of Gastroenterology, Gifu Municipal Hospital, Gifu, Japan
| | - Nobuhiko Hayashi
- Third Department of Internal Medicine, University of Toyama, Toyama, Japan
| | - Tsuyoshi Mukai
- Department of Gastroenterological Endoscopy, Kanazawa Medical University, Ishikawa, Japan
| | - Ichiro Yasuda
- Third Department of Internal Medicine, University of Toyama, Toyama, Japan
| | - Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
| | - Atsuhiro Masuda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
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Suzuki K, Hirata J, Okamura Y, Bando Y, Hara T, Terakawa T, Hyodo Y, Chiba K, Teishima J, Miyake H. Efficacy and Feasibility of Cabazitaxel for Very Elderly Patients of ≥ 80 Years of Age With Metastatic Castration-Resistant Prostate Cancer: A Real-World Multi-Intuitional Analysis. Prostate 2025; 85:814-820. [PMID: 40089975 DOI: 10.1002/pros.24889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 02/26/2025] [Accepted: 03/03/2025] [Indexed: 03/18/2025]
Abstract
BACKGROUND Cabazitaxel (CBZ) is a key drug used for metastatic castration-resistant prostate cancer (mCRPC). However, clinical trial data on CBZ in very elderly patients are still lacking. This study aimed to investigate the efficacy and feasibility of CBZ for mCRPC patients of ≥ 80 years of age. METHODS We retrospectively reviewed 484 patients with mCRPC who started CBZ treatment between September 2019 and March 2024. Therapeutic efficacy (PSA response, progression-free survival, overall survival, and safety profile) was compared between patients of < 80 years of age (< 80 group) and those of ≥ 80 years of age (≥ 80 group). In addition, risk factors associated with grade ≥ 3 neutropenia in the ≥ 80 group were investigated using a logistic regression model. RESULTS Seventy-three (15.1%) patients were included in the ≥ 80 group. Although more patients in the ≥ 80 group received a reduced dose relative to the < 80 group, there was no significant difference in therapeutic efficacy between the two groups. The incidence of grade ≥ 3 neutropenia was similar between two groups (< 80: 27.5% vs. ≥ 80: 31.5%). In the ≥ 80 group, BMI < 22 kg/m2 and neutrophil count ≤ 5000 cells/µL were significantly associated with grade ≥ 3 neutropenia, with odds ratios of 5.28 (p = 0.005) and 4.00 (p = 0.023), respectively. CONCLUSION In mCRPC patients of ≥ 80 years of age, CBZ showed similar safety and efficacy to younger patients. Our findings suggest that CBZ treatment with appropriate dose modification and prophylactic AE treatments may be still beneficial for elderly mCRPC patients in the current aging population.
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Affiliation(s)
- Kotaro Suzuki
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Junichiro Hirata
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yasuyoshi Okamura
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yukari Bando
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takuto Hara
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoaki Terakawa
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoji Hyodo
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Koji Chiba
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Jun Teishima
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideaki Miyake
- Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
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Tsuzuki N, Masuda K, Yamanobe Y, Mizuno K, Ozawa H, Wasano K. Idiopathic Sudden Sensorineural Hearing Loss Caused by Infarction of the Vestibulo-Cochlear Artery Can Be Detected by Testing Semicircular Canal Function and Audiometry: Proposal for Angiopathic Sudden Sensorineural Hearing Loss. Otol Neurotol 2025; 46:616-620. [PMID: 40059754 DOI: 10.1097/mao.0000000000004473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2025]
Abstract
BACKGROUND Although the specific pathogenesis of idiopathic sudden sensorineural hearing loss (ISSNHL) remains unknown, vascular impairment is one of the leading causes of ISSNHL. Establishing diagnostic criteria for ISSNHL due to vascular impairment is essential. We hypothesized that isolated posterior semicircular canal dysfunction (IPSCD) in ISSNHL patients results from infarction of the vestibulo-cochlear artery (VCA). The aim of this preliminary retrospective study is to identify possible diagnostic characteristics of ISSNHL patients with IPSCD. METHODS Seventeen ISSNHL patients were enrolled. They underwent video head impulse testing within 28 days of ISSNHL onset between September 2019 and November 2023. We obtained patient characteristics and clinical information, including results of audiometric and balance function tests. Eligible patients were divided into two groups according to the presence or absence of IPSCD. Patient characteristics and clinical information of the two groups were compared. RESULTS Of the 17 ISSNHL patients included, 6 had IPSCD. Compared to the 11 patients without IPSCD, the 6 patients with IPSCD had significantly more coronary artery disease (odds ratio, infinite; p = 0.03) and had regularly used antithrombotic medications (odds ratio, infinite; p < 0.01). The audiogram shapes of the six ISSNHL-IPSCD patients were profound, flat, or high-frequency descending forms. CONCLUSIONS Given that VCA impairment is associated with profound, flat, and high-frequency hearing loss and consistent with the arterial anatomy of the inner ear, ISSNHL-IPSCD patients are more likely to have vascular impairment. Conducting trials that target ISSNHL-IPSCD patients may lead to the discovery of new and effective treatments for ISSNHL.
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Affiliation(s)
| | - Kanako Masuda
- National Institute of Sensory Organs, NHO Tokyo Medical Center, Higashigaoka, Meguro, Tokyo, Japan
| | - Yoshiharu Yamanobe
- Department of Otolaryngology, NHO Tokyo Medical Center, Higashigaoka, Meguro, Tokyo, Japan
| | - Kohei Mizuno
- Department of Rehabilitation, NHO Tokyo Medical Center, Higashigaoka, Meguro, Tokyo, Japan
| | - Hiroyuki Ozawa
- Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Shinanomachi, Shinjuku, Tokyo, Japan
| | - Koichiro Wasano
- Department of Otolaryngology, Head and Neck Surgery, Tokai University School of Medicine, Shimokasuya, Isehara-city, Kanagawa, Japan
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Ueda T, Garnier E, Dellavale D, Bartolomei F, Bénar CG. Identification of the epileptogenic zone using phase-amplitude coupling on ictal stereoelectroencephalography. Clin Neurophysiol 2025; 174:151-159. [PMID: 40273618 DOI: 10.1016/j.clinph.2025.03.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 02/28/2025] [Accepted: 03/20/2025] [Indexed: 04/26/2025]
Abstract
OBJECTIVE Phase-Amplitude Coupling (PAC) has been proposed to characterize electrophysiological changes at seizure onset. However, PAC can arise from actual relations between oscillations at different frequencies (authentic PAC) or from harmonic/transient effects (spurious PAC). To assess the importance of these PAC mechanisms, we investigated the Modulation Index (MI) and Time Locked Index (TLI) between Epileptogenic Zone (EZ) and non-EZ channels during seizures. METHODS We analyzed 34 patients with drug-resistant epilepsy who underwent stereoelectroencephalography (SEEG) implantation. SEEG data was classified into three periods: "preictal," "fast," and "rhythmic." The amplitude of ripple bands and the phase of three slow-wave bands were used for MI and TLI. The capacity of MI to detect the EZ was tested with precision and recall measures, summarized by the F1 score. RESULTS The MI was significantly greater in EZ channels than that in non-EZ channels for all periods. The best F1 results were obtained for the "fast" period and spurious PAC. Both authentic and spurious PAC were present during all periods and bands. CONCLUSIONS Different PAC values could be observed during different seizure periods. Care should be taken when interpreting MI as a measure of authentic PAC. SIGNIFICANCE MI and TLI can help the interpretation of ictal cross-frequency observations.
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Affiliation(s)
- Tetsuya Ueda
- Department of Neurosurgery, Epilepsy Center, Juntendo University, Tokyo, Japan; Aix-Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France.
| | - Elodie Garnier
- Aix-Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France.
| | - Damián Dellavale
- Aix-Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro Atómico Bariloche, R8402AGP, San Carlos de Bariloche, Río Negro, Argentina.
| | - Fabrice Bartolomei
- Aix-Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France; APHM, Timone Hospital, Epileptology and Cerebral Rhythmology, Marseille, France.
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Toguchi K, Watanabe A, Horii M, Watanabe S, Itoh R, Sakamoto T, Murata Y, Ohtori S, Sasho T. Longitudinal Analysis of Knee Articular Cartilage Degeneration After Anterior Cruciate Ligament Reconstruction: Comparison of T1rho and T2 Mapping. Cartilage 2025; 16:125-138. [PMID: 39058092 PMCID: PMC11569521 DOI: 10.1177/19476035241264013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 06/06/2024] [Accepted: 06/07/2024] [Indexed: 07/28/2024] Open
Abstract
ObjectiveTo assess articular cartilage degeneration in anterior cruciate ligament (ACL) reconstructed knees as detected by MR T1rho and T2 mapping relative to controls and longitudinally at 3 months and 1 year after ACL reconstruction (ACLR).DesignTwenty-five patients with acute ACL injury were enrolled (13 women and 12 men; mean age 30.8), and 14 healthy controls were selected by sex and age matching. The affected knees of the ACLR participants were imaged using a 3.0T magnetic resonance (MR) scanner 3 months and 1 year after ACLR. Cartilage T1rho and T2 values were quantified for subcompartments in the full-thickness, superficial, and deep layers and were compared with the matched subcompartments of control knees. The influence of concomitant meniscal tears identified using proton density-weighted imaging (PDWI) was also investigated.ResultsIn the posterior lateral tibia, T1rho and T2 values were significantly higher in ACLR participants at 3 months and slightly decreased at 1-year compared to the control group. T1rho values in the medial compartment exhibited a significant increase at 1-year compared with those of control knees, while T2 showed no significance. In cartilage with medial meniscal tears, the T1rho values in multiple medial subcompartments were significantly higher than those in cartilage without medial meniscal tears, and this alteration was relatively detectable by T1rho.ConclusionsT1rho and T2 mapping is effective in evaluating cartilage degeneration following ACLR. T1rho may exhibit greater sensitivity for assessing the progression of early degeneration in the medial compartment after ACLR.
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Affiliation(s)
- Kaoru Toguchi
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Atsuya Watanabe
- Osteoarthritis Center, Medical Corporation Jyunhokai, Chiba, Japan
| | - Manato Horii
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shotaro Watanabe
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Ryu Itoh
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Takuya Sakamoto
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yasuaki Murata
- Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center, Chiba, Japan
| | - Seiji Ohtori
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
- Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
| | - Takahisa Sasho
- Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
- Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
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Ueda K, Imai T, Okayasu T, Tanaka T, Tatsumi K, Wanaka A, Kitahara T. Coenzyme Q10 and rikkunshito prevent age-related changes in mouse otolith morphology and function. Biochem Biophys Rep 2025; 42:102033. [PMID: 40384882 PMCID: PMC12084409 DOI: 10.1016/j.bbrep.2025.102033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 04/17/2025] [Accepted: 04/24/2025] [Indexed: 05/20/2025] Open
Abstract
Otoliths play an important role in maintaining body balance, and age-related decline in theis function and morphological integrity can lead to falls. In recent years, the herbal medicine rikkunshito (RKT) and the antioxidant coenzyme Q10 (CoQ10) have been studied for their anti-aging properties; however, their effects on otoliths remain unknown. Therefore, we aimed to investigate whether RKT and CoQ10 can prevent age-related functional and morphological changes in otoliths. To this end, 30 male and 30 female 8-week-old C57BL6N mice were used in this study. The mice were divided into three groups: a control group, CoQ10 group (0.2 % CoQ10 special diet), and RKT group (3 % RKT special diet). At 80 weeks of age, micro-computed tomography (μCT) images were taken and analyzed for otolith volume and CT number. Furthermore, eye movements induced by the linear vestibulo-ocular reflex (LVOR) were analyzed to assess otolith function. Results revealed that the RKT group had a significantly smaller volume of the 3 dimensional utriclar CT model (male mice; p = 0.0281, Steel test) and a significantly higher utricular CT number (male mice; p = 0.0104, Dunnett test) than the control group. The RKT group had a significantly weaker LVOR (male mice; lateral 1.3G stimulation; p = 0.00681, Dunnett test) (male mice; longitudinal 1.3G stimulation; p = 0.0183, Dunnett test) (male mice; longitudinal 0.7G stimulation; p = 0.00322, Dunnett test) than the control group. The CoQ10 group exhibited a significantly stronger utricle-induced LVOR than the control group (female mice; lateral 0.7G stimulation; p = 0.0133, Steel test).In conclusion, RKT prevented age-related utricular morphological changes, but did not prevent age-related otolith functional changes in male mice. CoQ10 prevented age-related utricular functional changes for low frequency stimulation in female mice.
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Affiliation(s)
- Keita Ueda
- Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Japan
| | - Takao Imai
- Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Japan
| | - Tadao Okayasu
- Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Japan
| | - Tatsuhide Tanaka
- Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Japan
| | - Kouko Tatsumi
- Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Japan
| | - Akio Wanaka
- Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Japan
| | - Tadashi Kitahara
- Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Japan
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Ogi Y, Oshikiri T, Egi H, Ishimaru K, Koga S, Yoshida M, Kikuchi S, Akita S, Matsumoto H, Sugishita H. A prospective study on the enhancement of surgical safety in robotic surgery: The BirdView camera system. Surg Today 2025; 55:746-753. [PMID: 39652249 DOI: 10.1007/s00595-024-02975-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 09/24/2024] [Indexed: 05/23/2025]
Abstract
PURPOSE To investigate the surgical safety and benefits of using the BirdView camera system with a wide field of view in robotic surgery for rectal cancer in a prospective clinical study. METHODS This study included 20 consecutive patients who underwent robotic surgery at our institution between the years 2022 and 2023. The primary endpoint was perioperative safety, which was defined as the occurrence of adverse events, including other organ injuries and malfunctions, caused by the BirdView camera system. RESULTS There were no injuries to any other organs caused by the console surgeon or assistant forceps during surgery. Surgical adverse events occurred in five cases (atelectasis, paralytic ileus, and anastomotic leakage) during the postoperative course. There were no cases of device failure or damage to the surrounding organs, including peritoneal heat damage. CONCLUSIONS We believe that the BirdView system could be valuable in improving the safety of robotic surgery by enabling the observation of blind spots, thus preventing harm to other organs.
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Affiliation(s)
- Yusuke Ogi
- Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Hospital, 454 Shitsukawa, Toon City, Ehime, 791-0295, Japan.
| | - Taro Oshikiri
- Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Hospital, 454 Shitsukawa, Toon City, Ehime, 791-0295, Japan
| | - Hiroyuki Egi
- Department of Surgery, Kitasato University Medical Center, 6-100 Arai, Kitamoto City, Saitama, 364-8501, Japan
| | - Kei Ishimaru
- Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Hospital, 454 Shitsukawa, Toon City, Ehime, 791-0295, Japan
| | - Shigehiro Koga
- Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Hospital, 454 Shitsukawa, Toon City, Ehime, 791-0295, Japan
| | - Motohira Yoshida
- Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Hospital, 454 Shitsukawa, Toon City, Ehime, 791-0295, Japan
| | - Satoshi Kikuchi
- Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Hospital, 454 Shitsukawa, Toon City, Ehime, 791-0295, Japan
| | - Satoshi Akita
- Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Hospital, 454 Shitsukawa, Toon City, Ehime, 791-0295, Japan
| | - Hironori Matsumoto
- Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Hospital, 454 Shitsukawa, Toon City, Ehime, 791-0295, Japan
| | - Hiroki Sugishita
- Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Hospital, 454 Shitsukawa, Toon City, Ehime, 791-0295, Japan
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Shimizu A, Shimoyama S, Ikeda K, Oka N. The Relationship Between the Positive Drain Tip Cultures and the Incidence of Surgical Site Infection After Pediatric Cardiovascular Surgery. Pediatr Infect Dis J 2025; 44:522-525. [PMID: 39823637 DOI: 10.1097/inf.0000000000004726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2025]
Abstract
BACKGROUND Surgical site infection (SSI) is a significant complication following pediatric cardiovascular surgery. Although drain tip cultures (DTC) are sometimes used postoperatively to predict SSIs, their diagnostic value in pediatric cardiovascular surgery remains unclear. This study aimed to assess the diagnostic utility of DTC for predicting SSIs in pediatric cardiovascular surgery patients. METHODS This retrospective, single-center cohort study was conducted at a tertiary children's hospital in Japan. We analyzed DTC and SSI data from pediatric patients who underwent cardiovascular surgery between December 2014 and August 2018. Demographic and clinical information was collected, and the incidence of SSIs was compared between patients with positive and negative DTC results. RESULTS A total of 555 samples from 254 patients were analyzed. DTC was positive in 70 samples (12.6%), and 27 patients (10.6%) had at least 1 positive DTC. The most frequently isolated organism was Staphylococcus epidermidis (n = 44), followed by Candida parapsilosis (n = 8), Staphylococcus lugdunensis (n = 4) and Staphylococcus aureus (n = 3). Twenty patients (7.9%) developed SSIs. The SSI rate was not significantly higher in patients with positive DTC compared with those with negative DTC (14.8% vs. 6.6%, P = 0.13). Only 2 cases showed concordance between the organisms detected in DTC and those responsible for SSIs. CONCLUSIONS The study found that positive DTC was not significantly associated with SSI occurrence after pediatric cardiovascular surgery. Therefore, routine culture of drainage tube tips may not be necessary unless there are clinical signs of infection. Further research is needed to evaluate the role of DTC in specific high-risk scenarios.
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Affiliation(s)
| | - Shinya Shimoyama
- Cardiovascular Surgery, Gunma Children's Medical Center, Gunma, Japan
| | - Kentaro Ikeda
- Cardiovascular Surgery, Gunma Children's Medical Center, Gunma, Japan
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Kato T, Watanabe H, Kawasumi Y, Kadomatsu Y, Ueno H, Nakamura S, Mizuno T, Chen-Yoshikawa TF. Impact of the expanded indication of robot-assisted thoracic surgery for mediastinal tumors. Gen Thorac Cardiovasc Surg 2025; 73:443-449. [PMID: 39467900 DOI: 10.1007/s11748-024-02093-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 10/04/2024] [Indexed: 10/30/2024]
Abstract
OBJECTIVE Following the introduction of robot-assisted thoracoscopic surgery (RATS) as a health insurance-covered treatment in Japan, we investigated the current status and impact of the expansion of the indications for RATS for mediastinal tumors. METHODS Between 2018 and 2022, 209 cases of total mediastinal tumor resection were performed in our hospital. The study period was divided into the first half (January 2018 to June 2020) and the second half (July 2020 to December 2022), and perioperative parameters were compared between the two groups. RESULTS Ninety-six surgical procedures were performed in the first half and 113 in the second half. The percentage of RATS approach was significantly higher in the second half compared with the first half (P < 0.001). Indications for RATS in the second half compared with the first half were significantly increased in patients with stage II (P < 0.001) and stage III (P = 0.026) thymomas, tumor diameter ≥ 50 mm (P < 0.011), and patients undergoing extended thymectomy for myasthenia gravis (P < 0.009). In respect of short-term postoperative parameters, the estimated intraoperative blood loss (P < 0.035), postoperative drain duration (P < 0.037), and postoperative hospital stay (P < 0.011) were significantly lower in the second half than in the first half. CONCLUSIONS RATS has recently been expanded for mediastinal tumors with improved short-term outcomes in our hospital after health insurance was applied in Japan. In the future, it will be necessary to discuss the further expansion of its indications by taking into account safety and long-term outcomes.
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Affiliation(s)
- Taketo Kato
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan
| | - Hiroki Watanabe
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan
| | - Yuta Kawasumi
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan
| | - Yuka Kadomatsu
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan
| | - Harushi Ueno
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan
| | - Shota Nakamura
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan
| | - Tetsuya Mizuno
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan
| | - Toyofumi Fengshi Chen-Yoshikawa
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan.
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Kuramochi T, Itaya T, Oshima Y, Kim J, Kitajima O, Nakamura T, Homma T, Ijichi H, Sano M, Suzuki T. Duloxetine improves hyperosmia in mice with pancreatic cancer by increasing dopamine levels in the olfactory bulb. Biomed Pharmacother 2025; 187:118098. [PMID: 40315673 DOI: 10.1016/j.biopha.2025.118098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 04/15/2025] [Accepted: 04/24/2025] [Indexed: 05/04/2025] Open
Abstract
The mechanism and therapeutic insights regarding hyperosmia to food odors in patients with cancer are poorly understood. We therefore evaluated the mechanism and effect of duloxetine in KPPC (LSL-KrasG12D/+; Trp53flox/flox; Pdx-1cre/+) mice with pancreatic cancer. Six-week-old KPPC mice were orally administered 4 mg/kg/day duloxetine (n = 7) or vehicle water (n = 6) daily until the humane endpoint. In healthy mice (n = 6), the buried pellet test (BPT) time was stable during the observation period, whereas BPT time was shortened in vehicle-treated KPPC mice, and this effect was inhibited by administration of duloxetine. The number of degenerated glomerular/mitral cells in the ventral olfactory bulb increased in vehicle-treated KPPC mice compared with healthy mice, and this effect was inhibited by duloxetine. Electron microscopic analysis revealed enlarged mitochondria in the degenerated neural cells. High-performance liquid chromatography analysis revealed a decrease in dopamine levels in the olfactory bulb of KPPC mice compared with healthy mice. The shortened BPT time in vehicle-treated KPPC mice was extended by L-dopa injection and wheel activity (n = 6 each). These findings suggest that duloxetine improves hyperosmia to food odors in mice with pancreatic cancer by increasing dopamine levels in the olfactory bulb.
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Affiliation(s)
- Tomoya Kuramochi
- Department of Obstetrics and Gynecology, Juntendo University, Urayasu Hospital, Chiba, Japan.
| | - Tomoaki Itaya
- Department of Anesthesiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Yukino Oshima
- Department of Anesthesiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Jinsuk Kim
- Department of Anesthesiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Osamu Kitajima
- Department of Anesthesiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Takahiro Nakamura
- Laboratory of Animal Physiology, School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan
| | - Taku Homma
- Department of Pathology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan
| | - Hideaki Ijichi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo, Japan; Clinical Nutrition Center, The University of Tokyo Hospital, Hongo, Tokyo, Japan
| | - Makoto Sano
- Department of Anesthesiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Takahiro Suzuki
- Department of Anesthesiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
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Tamaki Y, Hatayama N, Fujii Y, Naito M. A compact machine perfusion device for whole blood perfusion in isolated rat liver. J Artif Organs 2025; 28:244-251. [PMID: 39363050 DOI: 10.1007/s10047-024-01474-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 09/19/2024] [Indexed: 10/05/2024]
Abstract
We established a compact machine perfusion system for whole blood perfusion of rat liver by making use of oxygenation filters as an artificial lung. Livers removed from rats were divided into Krebs-Henseleit (control), 50% blood (hemoglobin: 7 g/dL), and whole blood (hemoglobin: 14 g/dL) groups, then perfused (total perfusate volume: 25 ml) with a small oxygenation filter at 37 °C for 120 min. Blood or perfusate was collected over time, and blood gas and blood cell were measured. In addition, bile volume and portal venous pressure measurements were taken. In all groups, the partial pressure of oxygen was controlled to approximately 400 mmHg. Flow rates were maintained at approximately about 20-30 ml/min according to liver size. Portal venous pressure was normal in the 50% blood and whole blood groups, while lower than the reference value in the Krebs-Henseleit group. Twice as much bile was produced in the 50% blood and whole blood groups relative with the Krebs-Henseleit group. We observed no differences in hemoglobin and red blood cell levels. Lactate levels were normal in the 50% blood and whole blood groups, but were elevated in the Krebs-Henseleit group. Our compact perfusion system using oxygenation filters was able to maintain rat liver function by perfusing a small amount of extracorporeal blood. This system is simple and stable, and may contribute to the future development of machine perfusion systems.
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Affiliation(s)
- Yuki Tamaki
- Department of Anatomy, Aichi Medical University, Nagakute, Aichi, 480-1195, Japan.
| | - Naoyuki Hatayama
- Department of Anatomy, Aichi Medical University, Nagakute, Aichi, 480-1195, Japan
| | - Yutaka Fujii
- Department of Clinical Engineering and Medical Technology, Niigata University of Health and Welfare, Niigata, Japan
| | - Munekazu Naito
- Department of Anatomy, Aichi Medical University, Nagakute, Aichi, 480-1195, Japan.
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