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Risa Hirata,1 Masaki Tago,1 Hiromizu Takahashi,2 Takashi Watari,3 Kiyoshi Shikino,4,5 Yosuke Sasaki,6 Taro Shimizu7 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan; 3Integrated Clinical Education Center, Kyoto University Hospital, Kyoto, Japan; 4Department of General Medicine, Chiba University Hospital, Chiba, Japan; 5Department of Community-Oriented Medical Education, Chiba University Graduate School of Medicine, Chiba, Japan; 6Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan; 7Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel: +81952343238, Fax +81952 342029, Email tagomas@cc.saga-u.ac.jpPurpose: General physicians are required to demonstrate diverse leadership skills depending on their environment. It is essential for them to understand the characteristics of the medical institutions to which they belong and put this understanding into practice. Leadership skills are acquired through experience and training, and their acquisition is a goal in various medical training programs. However, these leadership skills are difficult to acquire because the specific leadership skills required in clinical practice, education, and research are not well defined. For example, in clinical practice, general physicians need to lead initiatives to improve patient outcomes, resource utilization, and the quality of medical care. However, the specific leadership skills required for these tasks are not explicitly defined. Based on the survey results on the leadership types that general physicians value in clinical practice, research, and education, in addition to expert opinions and a literature survey, we aimed to establish the leadership type necessary in general medicine.Patients and Methods: A cross-sectional anonymous questionnaire survey was conducted from February 2 to 29, 2024, using Google Forms sent through email, targeting members of the Japan Society of Hospital General Medicine. The survey comprised multiple-choice and descriptive questions.Results: Notably, 286 physicians responded to the survey (response rate: 12.5%); 82.9% were males. Of these, 56.3% said they could explain what leadership constitutes, and 57.0% wanted to attend leadership training. When asked about the most-demanded leadership types in each scenario, democratic and transformational leadership were the most selected in clinical practice (52.4%) and in education and research (26.6% and 31.8%, respectively), respectively.Conclusion: Transformational leadership was the most important leadership type in education and research, indicating that many general physicians face challenges in these areas. Therefore, developing strategies to improve leadership skills in education and research within general medicine is crucial.Keywords: Democratic leadership, general medicine, leadership, transformational leadership

Yoshinori Tokushima,1,2 Risa Hirata,1 Shun Yamashita,1,3 Kiyoshi Shikino,4,5 Taro Shimizu,6 Masaki Tago1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Saga Medical Career Support Center, Saga University Hospital, Saga, Japan; 3Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, Japan; 4Department of General Medicine, Chiba University Hospital, Chiba, Japan; 5Department of Community-Oriented Medical Education, Chiba University Graduate School of Medicine, Chiba, Japan; 6Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpAbstract: Clinical reasoning skills are crucial for physicians. In clinical reasoning conferences using real cases, medical students, residents, and senior residents can follow experts’ clinical reasoning processes. However, supervisors may struggle to clearly articulate their clinical reasoning process. It is necessary to demonstrate this process concretely and systematically for educational purposes. This study introduces the method of clinical reasoning case conferences using semantic qualifiers and the dual-process theory designed for outpatient cases to improve clinical reasoning education methods for beginners. In these conferences, participants assume the roles of a moderator, learner, presenter, and commentator. The presenter sets the first semantic qualifier from the chief complaint and pre-examination information, presents the present illness history, and then sets the second semantic qualifier. After the learners propose a snap diagnosis, the presenter provides additional information, and the learners develop a comprehensive differential diagnosis. Finally, the presenter shares the examination results, and the group discusses the results, determines the final diagnosis, and decides the future diagnostic strategy. This method helps expert physicians articulate their clinical reasoning process, aiding in the education of learners at all levels and enhancing supervisors’ metacognition of their medical practice.Keywords: clinical reasoning, semantic qualifier, dual process theory, case conference, education

Takanobu Hirosawa,1,* Tomoharu Suzuki,2,* Tastuya Shiraishi,3,* Arisa Hayashi,1,* Yoichi Fujii,4,* Taku Harada,1,4,* Taro Shimizu1,* 1Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, Japan; 2Department of Hospital Medicine, Urasoe General Hospital, Okinawa, Japan; 3Higashinihonbashinaika clinic, Tokyo, Japan / Ubie, inc, Tokyo, Japan; 4General Medicine, Nerima Hikarigaoka Hospital, Tokyo, Japan*These authors contributed equally to this workCorrespondence: Takanobu Hirosawa, Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu-cho, Simotsuga-gun Tochigi, Tochigi, 321-0293, Japan, Tel +81-282-86-1111, Fax +81-282-86-4775, Email hirosawa@dokkyomed.ac.jpPurpose: Artificial intelligence (AI) holds great potential for revolutionizing health care by providing clinicians with data-driven insights that support more accurate and efficient clinical decisions. However, applying AI in clinical settings is often challenging due to the complexity and vastness of medical information. This perspective article explores how AI development methodologies can be adapted to support clinicians in their decision-making processes, emphasizing the importance of a hybrid approach that combines AI capabilities with clinicians’ expertise.Patients and Methods: We developed a conceptual framework designed to integrate AI-driven hybrid intelligence into clinical practice to enhance decision-making. This framework focuses on adapting key AI concepts, such as backpropagation, quantization, and avoiding overfitting, to help clinicians better interpret complex medical data and improve diagnosis and treatment planning.Results: Several AI methodologies were adapted to enhance clinical decision-making. First, backpropagation allows clinicians to refine initial assessments by revisiting them as new data emerges, improving diagnostic accuracy over time. Second, quantization helps break down complex medical problems into manageable components, enabling clinicians to prioritize critical elements of care. Finally, avoiding overfitting encourages clinicians to balance rare diagnoses with more common explanations, reducing the risk of diagnostic errors and unnecessary complexity.Conclusion: The integration of AI-driven hybrid intelligence has the potential to enhance clinical decision-making. By adapting AI methodologies, clinicians can enhance their ability to analyze data, prioritize treatments, and make more accurate diagnoses while preserving the essential human aspect of health care. This framework highlights the importance of combining AI’s strengths with clinicians’ expertise for more effective and balanced decision-making in clinical practice. This perspective highlights the value of hybrid intelligence in achieving more balanced, effective, and patient-centered decision-making in health care.Keywords: artificial intelligence, clinical reasoning, diagnostic accuracy, digital health, internal medicine, natural language processing

Masafumi Seki, Chie Kubosawa, Makoto Ono, Fumitaka Kamoshita, Atsuko Shimizu, Kotaro Mitsutake Division of Infectious Diseases and Infection Control, Saitama Medical University International Medical Center, Hidaka City, JapanCorrespondence: Masafumi Seki, Division of Infectious Diseases and Infection Control, Saitama Medical University International Medical Center, Yamane 1397-1, Hidaka City, Saitama, 350-1298, Japan, Tel +81-42-984-4392, Fax: +81-42-984-0280, Email sekimm@saitama-med.ac.jpBackground: Repeat positive results for SARS-CoV-2 by antigen detection test/RT-PCR in recovered COVID-19 patients were not very rare even when omicron variants became dominant, but the clinical features of patients with recurrent COVID-19 during hospitalization are still unclear.Methods: The clinical characteristics of patients with recurrent COVID-19 during hospitalization were retrospectively investigated from January 2023 to December 2023.Results: Recurrence of COVID-19 was found in 7 of 275 (2.5%) patients during hospitalization. Their mean age was 80.3 (74– 89) years, and 4 of 7 (57.1%) patients were hospitalized on the hematology ward with B cell/non-Hodgkin lymphoma. These 4 lymphoma patients had been vaccinated, but the other 3 patients hospitalized on the emergency ward and the neurology ward had not been vaccinated. Of the 7 patients, 6 (85.7%) were initially treated with remdesivir (RDV), but only 3 patients were re-treated with RDV, and the other 4 patients were successfully re-treated with oral 3C-like protease inhibitors, such as ensitrelvir (ESV) and nirmatrelvir/ritonavir (N/R).Conclusion: These data suggest that COVID-19 recurrence was found in patients with hematological disorders, such as lymphoma, and/or patients with no vaccination history. However, these patients were treated successfully by re-administration of anti-SARS-CoV-2 agents, including ESV and N/R.Keywords: SARS-CoV-2, remdesivir, nirmatrelvir/ritonavir, ensitrelvir, rituximab, Anti-CD20+ B cell depletion

Akira Kobayashi,1 Takahiko Hayashi,2 Ami Igarashi,2 Toshiki Shimizu,2 Hideaki Yokogawa,1 Kentaro Yuda,3 Björn Bachmann,4 Satoru Yamagami,2 Kazuhisa Sugiyama1 1Department of Ophthalmology, Kanazawa University Hospital, Ishikawa, Japan; 2Department of Ophthalmology and Department of Visual Sciences, Nihon University School of Medicine, Itabashi, Tokyo, Japan; 3Kikuna Yuda Eye Clinic, Yokohama, Japan; 4Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyCorrespondence: Akira Kobayashi, Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Takara-machi 13-1, Kanazawa, Ishikawa-ken, 920-8641, Japan, Tel +81-76-265-2403, Fax +81-76-222-9660, Email eyekoba@gmail.comBackground: Currently, the push-in technique through the corneal tunnel using a blunt-tip spatula is used to insert an artificial corneal endothelium (EndoArt) into the anterior chamber (AC). The device is useful for patients with bullous keratopathy; however, it may be difficult to manipulate the very thin implant through hazy cornea. Unlike DMEK graft, it cannot be stained and the F-mark is faint. So, visualizing and orienting the implant is a real challenge especially through a hazy cornea and inadequate AC visualization. Therefore, alternative EndoArt implantation techniques are needed in patients with advanced endothelial dysfunction to avoid complications.Purpose: To report an alternative technique for EndoArt implantation using a Busin glide.Technique: The EndoArt was loaded onto the Busin glide with the concave side of the EndoArt facing upward and was then pulled/pushed into the Busin glide opening. After the Descemet’s membrane and endothelium were detached and removed in a circular fashion in a patient with advanced corneal endothelial decompensation, the Busin glide was inserted into the corneal incision, and the EndoArt was slowly pulled into the AC using retractor forceps. Finally, the air was injected into the AC.Conclusion: The Busin glide-assisted pull-through technique smoothly and securely inserted the EndoArt into the AC without upside-down attachment. This alternative technique can be useful for patients with a history of repeat intraocular surgeries or trauma with severe corneal edema to avoid potential complications such as epithelial implantation cysts or downgrowth.Keywords: endothelial keratoplasty, artificial corneal endothelium, EndoArt, bullous keratopathy, Descemet’s membrane endothelial keratoplasty

Keita Okoshi,1 Shotaro Ito,1 Megumi Matsuoka,1 Yoshinori Kinugasa,1 Eri Shimizu,2 Kosei Tanaka,2 Joji Okada,3 Takahiro Nishizaka,1 Azumi Nagasawa,1 Tsuyoshi Seki,1 Makoto Iijima,1 Masatoshi Abe,4 Osamu Nemoto4 1Human Health Care Products Research, Kao Corporation, Tokyo, Japan; 2Analytical Science Research, Kao Corporation, Tochigi, Japan; 3Skin Care Products Research, Kao Corporation, Tokyo, Japan; 4Sapporo Skin Clinic, Sapporo, JapanCorrespondence: Azumi Nagasawa, Human Health Care Products Research, Kao Corporation, 2-1-3, Bunka, Sumida-ku, Tokyo, 131-8501, Japan, Tel +81-3-5630-7690, Fax +81-3-5630-9342, Email nagasawa.azumi@kao.comPurpose: Atopic dermatitis is characterized by chronic inflammation and dryness accompanied by severe itching. The combined use of moisturizers and topical anti-inflammatory drugs is essential for alleviating atopic dermatitis. We have developed a topical anti-inflammatory drug with a steroid and a moisturizer with heparinoid, both in lamellar structure-based formulations containing synthetic pseudo-ceramides. Here, assessed the efficacy of this combination in the treatment of atopic dermatitis.Methods: We included 22 patients with mild to moderate atopic dermatitis and subjected them to a seven-week treatment with the test formulations, followed by a four-week post-treatment period.Results: Clinical findings and the quality of life of participants remarkably improved after one week of treatment. Furthermore, skin hydration and transepidermal water loss considerably improved at weeks one and three, respectively. The Cer [NP]/[NS] ratio, an indicator of epidermal turnover, substantially increased during the treatment period and remained elevated even thereafter. The improvement in stratum corneum function was distinctive in participants with lower barrier function.Conclusion: These findings indicated that the combined use of the anti-inflammatory drug and moisturizer, both in lamellar structure-based formulations, is effective in treating atopic dermatitis in patients with fragile barrier function.Keywords: base formulations, lamellar structure, steroid, heparinoid, barrier function, TEWL

Risa Hirata,1 Masaki Tago,1 Kiyoshi Shikino,2,3 Takashi Watari,4 Hiromizu Takahashi,5 Yosuke Sasaki,6 Taro Shimizu7 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Chiba University Hospital, Chiba, Japan; 3Department of Community-Oriented Medical Education, Chiba University Graduate School of Medicine, Chiba, Japan; 4Integrated Clinical Education Center, Kyoto University Hospital, Kyoto, Japan; 5Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan; 6Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan; 7Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpPurpose: There has been growing interest in generalists in Japan in recent years. However, due to the diverse use of the term “generalist”, the specific roles of these physicians remain ambiguous. Consequently, the target population for research on generalists is unclear, making it challenging to conduct studies within the generalist practice framework. Therefore, a literature search was conducted to examine how generalists are defined and classified in research worldwide.Methods: We conducted a literature search that focused exclusively on articles written in English and used keywords related to generalists, general medicine (GM), primary care, and family medicine. Based on the results, six physicians working in GM reviewed the findings and discussed the identified issues and their potential solutions.Results: The definition of generalists in studies targeting GM, family medicine, and primary care conducted worldwide, including Japan, varies. Generalists exhibit diverse roles even within university hospitals in Japan. No studies provide a precise categorization or definition of generalists based on specific medical practices or roles, except for hospitalists, who are primarily involved in inpatient management in the United States.Conclusion: The definition of GM was unclear based on the results of the literature search, and the lack of uniformity in backgrounds has rendered the target population unclear. Consequently, in healthcare settings where medical systems vary by country or region, evidence from studies targeting generalists cannot readily apply to actual practice. Clarifying generalists through an explicit definition based on clinical practice will allow for a more precise target population for research on generalists and enable the accumulation of evidence related to well-defined groups of generalists, contributing to the advancement of GM. Therefore, future research is required to develop new indicators to precisely classify and define generalists.Keywords: generalist, general medicine, definition, hospitalist

Hirotaka Tashiro, Takashi Onoe, Naoki Tanimine, Sho Tazuma, Yoshiyuki Shibata, Takeshi Sudo, Haruki Sada, Norimitsu Shimada, Hirofumi Tazawa, Takahisa Suzuki, Yosuke Shimizu Department of Surgery, Kure Medical Center Chugoku Cancer Center, National Hospital Organization, Kure, Hiroshima, JapanCorrespondence: Hirotaka Tashiro, Department of Surgery, Kure Medical Center Chugoku Cancer Center, National Hospital Organization, 3-1, Aoyama, Kure, Hiroshima, 737-0023, Japan, Tel +823223111, Fax +823210478, Email tashiro.hirotaka.zn@mail.hosp.go.jpBackground: Posthepatectomy liver failure (PHLF) is a serious complication associated with high mortality rates. Machine learning (ML) has rapidly developed and may outperform traditional models in predicting PHLF in patients who have undergone hepatectomy. This study aimed to predict PHLF using ML and compare its performance with that of traditional scoring systems.Methods: The clinicopathological data of 334 patients who underwent liver resection were retrospectively collected. The Pycaret library, a simple, open-source machine learning library, was used to compare multiple classification models for PHLF prediction. The predictive performance of 15 ML algorithms was compared using the mean area under the receiver operating characteristic curve (AUROC) and accuracy, and the best-fit model was selected among 15 ML algorithms. Next, the predictive performance of the selected ML-PHLF model was compared with that of routine scoring systems, the albumin-bilirubin score (ALBI) and the fibrosis-4 (FIB-4) index, using AUROC.Results: The best model was extreme gradient boosting (accuracy:93.1%; AUROC:0.863) among the 15 ML algorithms. As compared with ALBI and FIB-4, the ML PHLF model had higher AUROC for predicting PHLF.Conclusion: The novel ML model for predicting PHLF outperformed routine scoring systems.Keywords: machine learning, posthepatectomy liver failure, liver cancer

Abstract Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Katsuhiko Shimizu,1 Masao Nakata,1 Shinsuke Saisho,1 Masayuki Inubushi,2 Norihito Okumura,3 Tomohiro Murakawa,4 Motohiro Yamashita,5 Hiroshige Nakamura,6 Yoshifumi Sano,7 Kazuhiko Kataoka,8 Shinichi Toyooka9 1Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Japan; 2Division of Nuclear Medicine, Department of Radiology, Kawasaki Medical School, Kurashiki, Japan; 3Department of Thoracic Surgery, Kurashiki Central Hospital, Kurashiki, Japan; 4Department of Thoracic Surgery, Kansai Medical University, Osaka, Japan; 5Department of Thoracic Surgery, Shikoku Cancer Center, Matsuyama, Japan; 6Division of General Thoracic Surgery, Tottori University Hospital, Yonago, Japan; 7Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Toon, Japan; 8Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan; 9Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, JapanCorrespondence: Katsuhiko Shimizu, Department of General Thoracic Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan, Tel +81-86-462-1124, Fax +81-86-464-1124, Email kshimizu@med.kawasaki-m.ac.jpBackground: Induction therapy followed by surgery is recommended as an alternative treatment strategy for locally advanced non-small cell lung cancer (NSCLC). Patients who achieve pathologic response after induction therapy have better outcomes than non-responders; therefore, therapeutic response must be evaluated. Recently, new approaches for monitoring therapeutic responses, which are based on 18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET), have been developed. In this study, we evaluated the predictive value of Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), which uses standardized uptake values corrected for lean body mass (SUL) and total lesion glycolysis (TLG).Methods: A total of 130 patients in the Setouchi Lung Cancer Group who underwent FDG-PET imaging before and after induction therapy prior to a planned surgical resection for NSCLC between 2007 and 2016 were studied retrospectively. The pathologic responses of the primary lung tumors and metastatic lymph nodes were compared with their responses based on evaluation using PERCIST.Results: Postoperative pathologic studies revealed pathologic complete response (pCR) in 42 (32.3%) patients. PERCIST was significantly correlated with pathologic response (p < 0.001). The sensitivity, specificity, and accuracy of PERCIST for predicting pCR were 16.7% (7/42), 88.6% (78/88), and 65.4% (85/130), respectively. Patients with pCR had significantly higher reduction rates in SULpeak for both primary lung tumors and metastatic lymph nodes and TLG for primary tumors than non-responders. In a multivariate Cox regression analysis, tumor site in upper lobes, reduction rate of TLG in primary tumor, and pathologic N0 were independent predictors of favorable recurrence-free survival (RFS).Conclusion: Our study suggested that PERCIST, especially the rate of TLG reduction rate, are useful to predict the pathological response and prognosis after induction therapy. Although improvement is necessary, PERCIST can be a promising method of the post-induction status in lung cancer. Further research is needed to confirm our findings.Keywords: non-small cell lung cancer, FDG PET, PERCIST, SUL, TLG

To clarify the changes in milk microbiota by lactation stage, i.e., d ays in milk (DIM) for Fresh of 0 to 21, Early (DIM of 22 to 80), Middle (DIM of 81 to 200), and Late (DIM 201 or more) lactation stages in dairy cows, we performed longitudinal (12 sampling at each stage, total 48 samples) and cross-sectional sampling (Fresh [n = 7], Early [n = 12], Middle [n = 11], and Late [n = 11] stages, total of 41 samples) to comprehensively analyze the microbiota in milk samples by 16S rRNA amplicon sequencing. Although the relative abundance of bacteria of the phylum Actinobacteria increased significantly in the Late lactation stage in the longitudinal study, no significant changes were observed in the cross-sectional study. While no changes were observed in the milk microbiota during the lactation stages, environmental factors appeared to have a comparatively larger impact than interindividual diversity on the composition of the milk microbiota. Furthermore, the findings illustrated the importance of selecting appropriate study designs to clarify changes in milk microbiota throughout the lactation period. The findings obtained in this study not only provide useful information for interpreting previous research results, but also provide knowledge that could be helpful when designing new studies.

Mermithidae is a family of nematodes that parasitize a wide range of invertebrates worldwide. Herein, we report nematodes that were unexpectedly found in three of 486 adult stable flies (Stomoxys calcitrans) captured from three farms (F1, F2, and F3) in different regions of Gifu Prefecture, Japan. We aimed to characterize these nematodes both at the morphological and molecular level. Morphological studies revealed that the nematodes were juveniles of Mermithidae. Phylogenetic analysis based on 18S and 28S rDNA indicated that the mermithids from farms F1 and F2 could be categorized into the same cluster as Ovomermis sinensis and Hexamermis sp., whereas the mermithid from farm F3 clustered with Amphimermis sp. Additionally, these mermithids could be categorized within the same clusters as related mermithids detected in Japan that parasitize various arthropod orders. Our findings suggest that these stable flies may have been parasitized by mermithids already present in the region and that genetically distinct species of mermithids occur across Japan. To the best of our knowledge, this is the first report of mermithids parasitizing adult stable flies in Japan.

Masaki Tago,1 Risa Hirata,1 Hiromizu Takahashi,2 Shun Yamashita,1,3 Masayuki Nogi,4,5 Kiyoshi Shikino,6 Yosuke Sasaki,7 Takashi Watari,8 Taro Shimizu9 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan; 3Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, Japan; 4Hospitalist Division, The Queen’s Medical Center, Honolulu, HI, USA; 5Department of General Internal Medicine, Kameda Medical Center, Chiba, Japan; 6Department of General Medicine, Chiba University Hospital, Chiba, Japan; 7Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan; 8General Medicine Center, Shimane University Hospital, Shimane, Japan; 9Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpAbstract: Hospital Medicine in the United States has achieved significant progress in the accumulation of evidence. This development has influenced the increasing societal demand for General Medicine in Japan. Generalists in Japan actively engage in a wide range of interdisciplinary clinical practices, education, and management. Furthermore, Generalists have also contributed to advances in research. However, there is limited evidence regarding the benefits of General Medicine in Japan in all these areas, with most of the evidence derived from single-center studies. In Japan, the roles of Generalists are diverse, and the comprehensive definition of General Medicine makes it difficult to clearly delineate its scope. This results in an inadequate accumulation of evidence regarding the benefits of General Medicine, potentially making it less attractive to the public and younger physicians. Therefore, it is necessary to categorize General Medicine and collect clear evidence regarding its benefits.Keywords: classification, evidence, general medicine

Risa Hirata,1 Masaki Tago,1 Kiyoshi Shikino,2,3 Takashi Watari,4 Hiromizu Takahashi,5 Yosuke Sasaki,6 Taro Shimizu7 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Chiba University Hospital, Chiba, Japan; 3Department of Community-Oriented Medical Education, Chiba University Graduate School of Medicine, Chiba, Japan; 4Integrated Clinical Education Center, Kyoto University Hospital, Kyoto, Japan; 5Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan; 6Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan; 7Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jp

Brazil is home to a great diversity of species of the genus Dyckia. However, many of these species are threatened due to habitat destruction and predatory exploitation. An alternative to conserving these plants is sexual propagation using plant regulators to stimulate germination. Gibberellic acid (GA3) is an effective regulator in this process, but its instability and ease of degradation pose challenges. Therefore, nanoencapsulation of GA3 could be used to protect the molecule and allow controlled release. In this study, the effects of different doses of GA3 were evaluated on the germination of four species: D. cabrerae, D. dusenii, D. pottiorum and D. walteriana. The first stage consisted of soaking the seeds in different concentrations of GA3, in which the species D. dusenii and D. walteriana showed significant responses to GA3, with an increase from 35% to more than 60% germination. However, the species D. cabrerae and D. pottiorum responded positively to GA3 only in vegetative growth parameters. In the second stage, the use of nanoparticles of alginate/chitosan (NP ALG/CS) and chitosan/tripolyphosphate (NP CS/TPP) containing GA3 was compared with free GA3 and with NPs without GA3. It was verified that the use of nanoencapsulated GA3 resulted in a more efficient germination response in D. walteriana seeds, using smaller doses of the regulator (between 0.75 mg · L−1 and 1.0 mg · L−1), mainly with the ALG/ CS NPs. Therefore, the use of GA3 is recommended for D. dusenii and D. walteriana, and for the latter, nanoparticles containing ALG/CS-GA3 allow a reduction in the required dose.

Yumi Otaka,1 Yukinori Harada,1 Norio Sugawara,2 Taro Shimizu,1 Norio Yasui-Furukori2 1Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, School of Medicine, Tochigi, Japan; 2Department of Psychiatry, Dokkyo Medical University, School of Medicine, Tochigi, JapanCorrespondence: Norio Yasui-Furukori, Department of Psychiatry, Dokkyo Medical University, School of Medicine, Mibu, Shimotsuga, Tochigi, 321-0293, Japan, Tel +81-282-86-1111, Fax +81-282-86-5187, Email furukori@dokkyomed.ac.jpBackground: Diabetic chorea is a rare complication of diabetes mellitus for which head MRI is the most common diagnostic imaging modality. Cases have been reported where CT and/or MRI findings are inconsistent or clinical symptoms and imaging findings do not appear simultaneously. We aimed to compile the cases in which imaging findings appeared on MRI retests and to examine in a systematic review whether temporal differences in the appearance of imaging findings correlate with clinical characteristics.Case Presentation: An 80-year-old man with type 2 diabetes mellitus came to a hospital with abnormal movements of the left upper and lower extremities. Two days after the first visit, his symptoms flared up, and his head MRI showed an old cerebral infarction and no new lesion. On day 14, he retested T1-weighted imaging and showed a high signal in the right putamen, which was considered diabetic chorea. Blood glucose was controlled with insulin, and the involuntary movements disappeared.Methods: PubMed and ICHUSHI were searched to identify patients with diabetic chorea who had undergone MRI retests. Patients grouped by the temporal change in the presence/absence of imaging findings were compared on age, sex, duration of diabetes mellitus, blood glucose level, HbA1c level, side of involuntary movement, time to first MRI, and follow-up MRI.Results: Of the 64 cases analyzed, 43 (67.2%) were female. The mean age was 69.0 years. 16 (25.0%) had worsening findings upon MRI retesting, 37 (57.8%) had improvement, and 10 (15.6%) had unchanged findings. There were no significant differences in age, sex, mean blood glucose level or HbA1c at onset among the groups.Conclusion: There was no association between the pattern of appearance of imaging findings over time and clinical characteristics, including glucose levels. If initial MRI findings are negative, MRI retesting after a certain time may help diagnose diabetic chorea.Keywords: hyperglycemia, hemichorea, hemiballismus, diabetes, movement disorders

Abstract Background This study presents the clinical pattern of presentation and survival rate of retinoblastoma, which is the most prevalent form of pediatric intraocular cancer. The aim of this study is to provide baseline information about the clinical presentation and management of retinoblastoma at ECWA Eye Hospital. Additionally, the study identifies priority areas for enhancing medical care for children diagnosed with this cancer. ECWA Eye Hospital, situated in Kano State, Nigeria, is a specialized eye center located in the North-Western region of the country. Methods A prospective study spanning five years was conducted at ECWA Eye Hospital to investigate clinically diagnosed cases of retinoblastoma. The study took place from January 2018 to December 2022. The patients received standardized pre-medication and chemotherapy protocols for retinoblastoma. Subsequently, a five-year follow-up was conducted to monitor the patients’ progress. The collected data was analyzed, descriptive statistics were generated, and the survival rate was calculated. Results During the five-year study period, a total of 35 cases of retinoblastoma were diagnosed. The patients had an average age of 3.21 ± 1.32 years. The most common presentation patterns observed were fungating ocular mass and proptosis. Among the cases, there were 10 instances of bilateral proptosis and 25 instances of unilateral proptosis. While no patients exhibited bilateral leukocoria, eight cases of unilateral leukocoria with anterior segment seedlings were identified. The additional patterns of presentation are proptosis, leukocoria, fungating orbital mass, redness and loss of vision. The mortality rate was 80% (28 cases), while the survival rate was 20% (7 cases). Notably, all the survivors had unilateral retinoblastoma. Conclusion The majority of cases observed at ECWA Eye Hospital involve advanced retinoblastoma. In low-resource settings where alternative treatment options are limited, chemotherapy is considered a viable treatment option. Early presentation of retinoblastoma in patients may lead to a higher survival rate when chemotherapy is administered.

Yoshihisa Ishiura, Shosaku Nomura, Yuka Ishii, Kai Imai, Yusuke Sawai, Takeshi Tamaki, Toshiki Shimizu, Naoyuki Miyashita, Tomoki Ito First Department of Internal Medicine, Kansai Medical University, Osaka, JapanCorrespondence: Yoshihisa Ishiura, First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan, Tel +81-6-6992-1001, Fax +81-6-6993-9837, Email ishiuray@takii.kmu.ac.jpAbstract: Cough, a frequent symptom encountered in clinical practice, often has a considerable impact on patients’ lives. There is an urgent need to investigate more potent antitussive treatments for chronic refractory cough, particularly atopic cough, which is a major cause of chronic refractory cough in Japan. Previous studies have shown that eosinophilic tracheobronchitis with hypersensitivity to sensory nerve C-fibers is the pathophysiology of atopic cough. Gefapixant is a first-in-class P2X3 antagonist that has recently become available for clinical use in patients with refractory coughs. A 64-year-old female non-smoker presented to our hospital with a complaint of chronic intractable cough due to atopic cough. Addition of gefapixant (90 mg/day) to her previous treatment improved her distressing cough, despite the partial efficacy of many other drugs. The findings of this case demonstrate that P2X3 inhibition is a viable therapeutic option for patients with chronic refractory cough caused by atopic cough. This case report offers valuable information regarding currently available treatment options for refractory chronic refractory cough caused by atopic cough. There remains an urgent need to clarify the disease entities presenting with chronic cough that can be effectively treated by inhibiting P2X3.Plain Language Summary: There is an urgent need to investigate more potent antitussive treatments for chronic refractory cough, because cough has a considerable impact on patients’ lives. Previous studies have shown that eosinophilic tracheobronchitis with hypersensitivity of sensory nerve C-fibers is the pathophysiology of atopic cough, which is a major cause of chronic cough in Japan. Gefapixant is a first-in-class P2X3 antagonist that has recently become available for clinical use in patients with refractory coughs. Herein, we present the case of a 64-year-old female with a refractory atopic cough. The gefapixant add-on improved her distressing cough, indicating that P2X3 inhibition could be a viable therapeutic option for patients with chronic refractory cough caused by atopic cough.Keywords: chronic cough, atopic cough, gefapixant, P2X3

Yuki Ikeda,1 Masahiro Iwakawa,1 Hajime Kiyokawa,1 Takahiro Nakagami,1 Shinya Kanzaki,2 Akihiro Ogawa,2 Tsuyoshi Tabata,3 Mao Takahashi,1 Toshio Kinoshita,1,3 Kazuhiro Shimizu1 1Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan; 2Department of Rehabilitation, Toho University Sakura Medical Center, Chiba, Japan; 3Department of Clinical Functional Physiology, Toho University Sakura Medical Center, Chiba, JapanCorrespondence: Kazuhiro Shimizu, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan, Tel +81-43-462-8811, Fax +81-43-462-8820, Email k432@sakura.medtoho-u.ac.jpAbstract: Obesity-induced heart failure (HF) in young people is a serious problem. The treatments for HF have developed in recent years. The following four basic HF drugs have been widely recognized as the “Fantastic Four”: beta-adrenergic blocking agents, mineralocorticoid receptor antagonists (MRA), sodium glucose transporter 2 inhibitors (SGLT2 inhibitors), and angiotensin receptor neprilysin inhibitors (ARNI). However, the interaction between the heart and blood vessels has not received much attention. The cardio-ankle vascular index (CAVI) is an arterial stiffness index that is unaffected by blood pressure at the time of measurement. A 34-year-old obese man was admitted with dyspnea and edema. His cardiac function was severely impaired, and CAVI was increased. After administration of multidisciplinary HF treatment centered on the “Fantastic Four”, his cardiac function and CAVI improved dramatically in a short time period. This case suggests the importance of improvement both cardiac and vascular function for the treatment of HF.Keywords: obesity, hypertension, obstructive sleep apnea, arterial stiffness, cardio ankle vascular index

Dai Shimizu,1 Chie Tanaka,1 Mitsuro Kanda,1 Koki Nakanishi,1 Seiji Ito,2 Yachiyo Kuwatsuka,3 Masahiko Ando,3 Kenta Murotani,4 Michitaka Fujiwara,5 Yasuhiro Kodera1 1Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan; 2Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan; 3Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; 4Biostatistics Center, Graduate School of Medicine, Kurume University, Kurume, Japan; 5Department of Medical Equipment and Supplies Management, Nagoya University Hospital, Nagoya, JapanCorrespondence: Dai Shimizu, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan, Tel +81-52-744-2249, Fax +81-52-744-2255, Email d-shimizu@med.nagoya-u.ac.jpAbstract: Pancreatic fistula after gastrectomy with lymph node dissection is associated with prolonged hospital stay and critical complications such as intra-abdominal bleeding and sepsis. Polyglycolic acid (PGA) sheets are absorbable suture reinforcement materials. A randomized Phase II trial has been planned to evaluate the effect of PGA sheets on preventing postoperative pancreatic fistula. A total of 320 patients will be recruited from thirteen institutions. Patients who are scheduled to undergo distal or total gastrectomy will be randomly allocated into the PGA group or control group, and the dissected area around the pancreas will be covered by the PGA sheet in the PGA group. The primary endpoint will be the maximum value of drain amylase concentration up to 5 days after surgery. The secondary endpoints will be as follows: transition of value of amylases of drain discharge, incidence of pancreatic fistula, incidence of intra-abdominal abscess, white blood cell count, value of C-reactive protein, incidence of postoperative complication, duration of antibiotic agents administration, duration of abdominal drainage, usage of octreotide, duration of hospital stay, incidence of bleeding in abdominal cavity, mortality, and incidence of reoperation.Keywords: gastric cancer, pancreatic fistula, polyglycolic acid sheet, protocol, randomized clinical trial

Masaki Tago,1 Risa Hirata,1 Naoko E Katsuki,1 Yuki Otsuka,2 Taro Shimizu,3 Yosuke Sasaki,4 Kiyoshi Shikino,5 Takashi Watari,6 Hiromizu Takahashi,7 Kazunobu Une,8 Toshio Naito,7 Fumio Otsuka,2 Rachel Thompson,9 Susumu Tazuma8,10 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 3Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, Japan; 4Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan; 5Department of General Medicine, Chiba University Hospital, Chiba, Japan; 6General Medicine Center, Shimane University Hospital, Izumo, Japan; 7Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 8Department of Critical Care and General Medicine, Onomichi General Hospital, Hiroshima, Japan; 9Executive Team, Snoqualmie Valley Hospital, Snoqualmie, WA, USA; 10JR Hiroshima Hospital, Hiroshima, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpIntroduction: Hospitalists in Japan have been at the forefront of the COVID-19 pandemic. However, contributions of Japanese hospitalists during the COVID-19 pandemic and hospitalists’ awareness of crisis management education remain unclear.Material and Methods: We conducted a questionnaire survey to investigate the role of Japanese hospitalists during the COVID-19 pandemic. The questionnaire was conducted using email and Google Forms targeting the chairpersons of facilities certified by the Japanese Society of Hospital General Medicine (JSHGM). Members of the academic committee of the JSHGM and several hospitals conducted a narrative review and determined the questions for the survey in a discussion.Results: We conducted descriptive statistics based on the responses of 97 hospitals that agreed to participate in this survey. In total, 91.8% of general medicine departments in the included hospitals were involved in the medical care of COVID-19 patients. Furthermore, in 73.2% of hospitals, hospitalists were involved in infection control for COVID-19 inside or outside the hospital. Our survey revealed that Japanese hospitalists were responsible for COVID-19 treatment in over 60% of hospitals and contributed to hospital management, infection control, and vaccination. In total, 79.4% of hospitals answered that “training of personnel who can provide practical care for emerging infectious diseases is necessary”, 78.4% indicated that “the establishment of an infection control system in advance to prepare emerging infectious diseases in the hospital is necessary”, and 74.2% stated that “the establishment of an educational system for responding to emerging infectious diseases is necessary.”.Conclusion: In conclusion, during the pandemic, in addition to inpatient care, Japanese hospitalists provided outpatient care for COVID-19, which is the role of primary care physicians in other countries. Furthermore, Japanese hospitalists who experienced the COVID-19 pandemic expressed the need for personnel development and education to prepare for future emerging infectious disease pandemics.Keywords: COVID-19 pandemic, hospitalist, hospital management

Kazuhiro Shimizu,1 Tsuyoshi Tabata,2 Masahiro Iwakawa,1 Shuji Sato,1 Toshio Kinoshita1,2 1Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan; 2Department of Clinical Functional Physiology (Sakura), Toho University Sakura Medical Center, Chiba, JapanCorrespondence: Kazuhiro Shimizu, Department of Internal Medicine, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, 285-8741, Japan, Tel +81-43-462-8811, Fax +81-43-462-8820, Email k432@sakura.med.toho-u.ac.jpAbstract: A 72-year-old man presented to our clinic with hypertension. Arterial stiffness evaluated by cardio ankle vascular index (CAVI) was markedly increased at 13.5. We treated him using 80 mg/day of valsartan for three months. CAVI was decreased from 13.5 to 13.0. However, his BP fluctuations were still high. We changed the treatment to angiotensin receptor-neprilysin inhibitor (ARNI) with increasing doses up to 400 mg. Independent of the change in blood pressure at the time of measurement, CAVI improved with ARNI dose. Hypertension treatment with an awareness of the cardio-vascular interaction might be a possibility prevents future heart failure development effectively.Keywords: hypertension, angiotensin receptor-neprilysin inhibitor, arterial stiffness, cardio ankle vascular index

Ariesanti Tri Handayani,1 Clara Valentina,1 I Gusti Ayu Ratna Suryaningrum,1 Putu Dian Megasafitri,1 I Gusti Ayu Made Juliari,1 Ida Ayu Ary Pramita,1 Shintaro Nakayama,2,3 Eisuke Shimizu,2,3 Anak Agung Mas Putrawati Triningrat1 1Ophthalmology Study Program Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia; 2Department of Ophthalmology, Keio University School of Medicine, Shinjuku, Tokyo, Japan; 3OUI Inc ., Minato, Tokyo, JapanCorrespondence: Ariesanti Tri Handayani, Ophthalmology Study Program Faculty of Medicine, Udayana University, Jl. Diponegoro, Dauh Puri Klod, Kec, West Denpasar, Denpasar City, Bali, 80113, Indonesia, Tel +62818-375611, Email ariesanti@unud.ac.idIntroduction: Dry eye disease (DED) is a multifactorial disease of tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability leading to decrease of vision, productivity and quality of life, and blindness. DED diagnosis remains difficult and underdiagnosed regarding inconsistency between subjective symptoms and clinical findings. Tear break-up time (TBUT) is an objective indicator of tear film stability in diagnostic DED. A novel smartphone attachment, namely SEC (smart eye camera), could mimic conventional slit lamp to assess TBUT and beneficial in facilitating DED diagnosis. Reliability between a non and an ophthalmologist in TBUT assessment and DED diagnosis is observed in this study.Purpose: To determine interobserver reliability of TBUT measurement for diagnosing DED using SEC.Design: This a cross-sectional analytic study involving 99 participants (198 eyes) aged 40 years who visited Pratama Gema Santi Hospital, Nusa Penida, from September 2nd to 4th, 2022, with consecutive sampling technique.Methods: Fluoresceined eyes were filmed using the SEC device and apps, continued by masked ophthalmologist and resident assessing TBUT based on the video. The primary outcome is interobserver reliability for TBUT measurement and DED diagnosis.Results: The mean age of participants was 55.22± 9.78 years, 48.5% male and 51.5% female. The reliability of interobserver in assessing DED based on TBUT test is 0.78 (95% CI=0.31– 1.26, P-value=0.001), and interobserver reliability in diagnosing DED based on OSDI and TBUT showed good agreement (weighted kappa=0.71). Good interobserver reliability underscores that non-ophthalmologists can diagnose DED based on TBUT video using SEC.Conclusion: SEC video has good interobserver reliability to assess TBUT for DED diagnosis. SEC can be used as one of the methods in assessing DED in limited health care facilities. The high reliability of interobserver assessment indicates that DED diagnosis using video taken with SEC may be useful for telemedicine evaluation in remote areas.Graphical Abstract: Keywords: dry eye disease, smart eye camera, telemedicine

Masaki Tago,1 Risa Hirata,1 Kiyoshi Shikino,2 Takashi Watari,3 Yosuke Sasaki,4 Hiromizu Takahashi,5 Taro Shimizu6 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Chiba University Hospital, Chiba, Japan; 3General Medicine Center, Shimane University Hospital, Shimane, Japan; 4Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan; 5Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 6Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpAbstract: Clinical physicians have the potential to contribute to the progress of medicine and healthcare through research based on their diagnostic and treatment practices and supported by their educational background. However, in the field of general medicine in Japan, publication of such research in international journals may be limited by challenges in English proficiency and the lack of opportunities to focus on specific research themes amidst the diverse range of diseases treated in clinical practice. Furthermore, novice researchers without prior research experience may lack a comprehensive understanding of the overall research process, including study design and article publication. To address these challenges, we developed a set of 22 milestones that highlight the necessary skills required to conduct and successfully publish clinical research. This guideline will enable novice researchers to identify and address individual barriers to undertaking a research project. These milestones are categorized into five parts: 1) preparing to undertake research; 2) conducting clinical research; 3) writing the article; 4) submitting and achieving acceptance for publication; and 5) advanced skills. For each part, we provide detailed recommendations on the specific steps and methods involved. By working through these 22 milestones, novice researchers can objectively assess their own level of achievement as researchers and continuously clarify the next step of each round of research. Through this set of milestones, we aim to increase the quality and quantity of research publications in general medicine in academic journals, ideally enhancing the overall research process and advancing the field of medicine and healthcare overall.Keywords: clinical research, original research, young physicians

Takanobu Hirosawa,1 Tetsu Sakamoto,1 Shogo Hanai,2 Yukinori Harada,1 Taro Shimizu1 1Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Shimotsuga, Tochigi, Japan; 2Departments of Microbiology and Infectious Diseases, Fujita Health University School of Medicine, Aichi, JapanCorrespondence: Takanobu Hirosawa, Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu-cho, Shimotsuga, Tochigi, 321-0293, Japan, Tel +81 282 87 2498, Fax +81 282 87 2502, Email hirosawa@dokkyomed.ac.jpPurpose: The effect of antibiotics administered before blood cultures performed in general internal medicine outpatient settings is not well known.Patients and Methods: We conducted a retrospective case–control study including adult patients who underwent blood cultures in the general internal medicine outpatient department of a Japanese university hospital between 2016 and 2022. Patients with positive blood cultures were included as cases and matched patients with negative blood cultures were included as controls. Univariable and multivariable logistic regression analyses were performed.Results: A total of 200 patients and 200 controls were included. Antibiotics were administered prior to blood culture in 20% of patients (79/400). Oral antibiotics were prescribed to 69.6% of the prior antibiotics (55/79). Prior antibiotic use was significantly lower among patients with positive than negative blood cultures (13.5% vs 26.0%, p = 0.002) and was an independent predictive factor in univariable (odds ratio, 0.44; 95% confidence interval, 0.26– 0.73; p = 0.002) and multivariable (adjusted odds ratio, 0.31; 95% confidence interval, 0.15– 0.63; p = 0.002) logistic regression models for positive blood culture. The area under the receiver operating characteristic (AUROC) curve of the multivariable model for predicting positive blood cultures was 0.86.Conclusion: There was a negative correlation between prior antibiotic use and positive blood cultures in the general internal medicine outpatient department. Therefore, physicians should interpret the negative results of blood cultures performed after the administration of antibiotics with care.Keywords: bacteremia, fever, infection, antibacterial agent, antimicrobial, sepsis

Takahira Kuno,1,2 Kenji Tamura,1,3 Nobutaka Shimizu,1 Hideo Fukuhara,1 Satoshi Fukata,1 Shingo Ashida,1 Takashi Karashima,1 Hirofumi Satake,3 Kohji Sawada,4 Ichiro Yamasaki,5 Fumito Komatsu,2 Hajime Kuroiwa,6 Motoaki Saito,7 Keiji Inoue1 1Department of Urology, Kochi Medical School, Kochi University, Nankoku, Japan; 2Department of Urology, Tosa Municipal Hospital, Tosa, Japan; 3Department of Urology, Chikamori Hospital, Kochi, Japan; 4Department of Urology, Kochi Prefectural Hata Kenmin Hospital, Sukumo, Japan; 5Department of Urology, Kubokawa Hospital, Takaoka-gun, Japan; 6Integrated Center for Advanced Medical Technologies (ICAM-Tech), Kochi Medical School, Nankoku, Japan; 7Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, JapanCorrespondence: Kenji Tamura, Email tamurak@kochi-u.ac.jpObjective: The treatment effects of vibegron have not previously been evaluated in a prospective, non-interventional observational study of elderly Japanese patients, particularly those ≥ 80 years old. In addition, no reports have referred to residual urine volume in switching cases. We therefore grouped patients by condition and investigated the treatment effects of vibegron on Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Short Form (OAB-q SF), and residual urine volume in each group.Methods: This multicenter, prospective, non-interventional, observational study consecutively enrolled OAB patients with total OABSS score ≥ 3 and OABSS question 3 score ≥ 2. Sixty-three patients from six centers were recruited. Vibegron 50 mg once daily was administered for 12 weeks as first-line monotherapy (first-line group), monotherapy switching from antimuscarinics or mirabegron due to failure of prior therapy (no washout period), or combination therapy with antimuscarinics (second-line group). OABSS, OAB-q SF, and residual urine volume were collected after 4 and 12 weeks. Adverse events were also recorded at each visit.Results: Of the 63 patients registered, 61 were eligible for analysis (first line, n=36; second line, n=25). The OABSS, excluding daytime frequency scores, and OAB-q SF scale showed significant improvement in all conditions. Switching from mirabegron to vibegron significantly reduced residual urine volume. No serious treatment-related adverse events were encountered.Conclusion: Vibegron 50 mg once daily significantly improved OABSS and OAB-q SF even in patients ≥ 80 years old. Notably, switching from mirabegron to vibegron resulted in significant improvements to residual urine volume.Keywords: selective β 3-adrenoreceptor agonist, overactive bladder, residual urine volume, vibegron, mirabegron

Ren Kawamura, Yukinori Harada, Masashi Yokose, Shogo Hanai, Yudai Suzuki, Taro Shimizu Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Mibu, Tochigi, JapanCorrespondence: Taro Shimizu, Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, 880 Kitakobayashi, Shimotsuga, Mibu, Tochigi, 321-0293, Japan, Tel +8128286-1111, Email shimizutaro7@gmail.comPurpose: The general internal medicine (GIM) department can be an effective diagnostic coordinator for undiagnosed outpatients. We investigated the contribution of GIM consultations to the diagnosis of patients admitted to specialty departments in hospitals in Japan that have not yet adopted a hospitalist system.Patients and Methods: This single-center, retrospective observational study was conducted at a university hospital in Japan. GIM consultations from other departments on inpatients aged ≥ 20 years, from April 2016 to March 2021, were included. Data were extracted from electronic medical records, and consultation purposes were categorized into diagnosis, treatment, and diagnosis and treatment. The primary outcome was new diagnosis during hospitalization for patients with consultation purpose of diagnosis or diagnosis and treatment. The secondary outcomes were the purposes of consultation with the Diagnostic and Generalist Medicine department.Results: In total, 342 patients were included in the analysis. The purpose of the consultations was diagnosis for 253 patients (74%), treatment for 60 (17.5%), and diagnosis and treatment for 29 patients (8.5%). In 282 consultations for diagnosis and diagnosis and treatment, 179 new diagnoses were established for 162 patients (57.5%, 95% confidence interval [CI], 51.5– 63.3).Conclusion: The GIM department can function as a diagnostic consultant for inpatients with diagnostic problems admitted to other specialty departments in hospitals where hospitalist or other similar systems are not adopted.Keywords: diagnosis, diagnostic excellence, consultation, consultative medicine, hospital admission

Shunsuke Sakakura,1,&ast; Fumihiro Yamaguchi,1,&ast; Takashi Abe,1 Hidekazu Cho,1 Shohei Shimizu,1 Ayaka Mase,1 Yusuke Shikama,1 Haruhiko Maruyama2 1Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan; 2Division of Parasitology, Department of Infectious Diseases, Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki, Japan&ast;These authors contributed equally to this workCorrespondence: Fumihiro Yamaguchi, Department of Respiratory Medicine, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, 227-8501, Japan, Tel +81-45-971-1151, Email f_y@med.showa-u.ac.jpAbstract: The Paragonimus westermani infection is a parasitic foodborne infection that induces systemic symptoms with eosinophilia in humans. Here, we described pneumothorax in addition to pulmonary opacities with eosinophilia in a man with a positive P. westermani serology. He was misdiagnosed with chronic eosinophilic pneumonia (CEP) during the initial phase. Paragonimiasis can share similar clinical findings with CEP in cases where the worm is confined to the lungs. The findings of the current study suggest that paragonimiasis and CEP can be distinguished from each other by the presence of various symptoms. Notably, eosinophilia with pneumothorax should be an important diagnostic factor for paragonimiasis.Keywords: Paragonimus westermani, chronic eosinophilic pneumonia, paragonimiasis, pneumothorax

Taro Shimizu Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Mibu, Tochigi, JapanCorrespondence: Taro Shimizu, Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Dokkyo Medical University, Graduate School of Medicine, Kitakobayashi 880, Mibu, Tochigi, 321-0293, Japan, Email shimizutaro7@gmail.comAbstract: Diagnostic excellence is an important goal in medicine. The enhancement of clinical reasoning skills of physicians, which is at the core of this concept, is a significant challenge. To achieve this improvement, it is necessary to enhance the ability to collect patient history information and to integrate the information. Additionally, the complexity of diagnosis is confounded by biases, noise, uncertainty, and contextual factors, and the impact of these factors is particularly prominent in complex cases. In such cases, the dual process theory, which is a classical reasoning measure, alone is insufficient to cope with these challenges, and a multifaceted and comprehensive approach is required to supplement its limitations. Therefore, the author presents six concrete steps, represented by the acronym DECLARE (Decomposition, Extraction, Causation Link, Assessing Accountability, Recomposition, Explanation and Exploration), that implement the concept of cognitive forcing strategy that has been shown to be effective in bias control, and include reflection, meta-cognition, and the recently popularized decision hygiene procedure. DECLARE is a strategy that should be deployed when faced with more complex diagnostic scenarios. By examining each of the six steps that comprise DECLARE individually, cognitive load can be reduced. Furthermore, by verifying causation and accountability when constructing diagnostic hypotheses, biases can be mitigated, which can also help to address noise and uncertainty, leading to an improvement in the quality of diagnosis and effectiveness in medical education.Keywords: diagnostic excellence, diagnostic strategy, meta-cognition, reflection, causal inference, decision hygiene

Masahisa Arahata,1,2 Hidesaku Asakura,3 Eriko Morishita,4 Shinji Minami,2 Yukihiro Shimizu2 1Department of General Medicine, Nanto Municipal Hospital, Nanto, Toyama, Japan; 2Department of Internal Medicine, Nanto Municipal Hospital, Nanto, Toyama, Japan; 3Department of Hematology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan; 4Department of Clinical Laboratory Science, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, JapanCorrespondence: Masahisa Arahata, Department of Internal Medicine, Nanto Municipal Hospital, 938 Inami, Nanto, Toyama, 932-0211, Japan, Tel +81 763 82 1475, Fax +81 763 82 1853, Email rqxhf297@yahoo.co.jpPurpose: Prognostic uncertainty can be a barrier to providing palliative care. Accurate prognostic estimation for patients at the end of life is challenging. This study aimed to evaluate the accuracy of end-of-life diagnosis using our unique diagnostic method.Patients and Methods: A retrospective longitudinal observational study was conducted through collaboration among three medical facilities in a rural super-aged community in Japan. In 2007, we established a unique end-of-life diagnostic process comprising (1) physicians’ judgement, (2) disclosure to patients, and (3) discussion at an end-of-life case conference (EOL-CC), based on Japanese end-of-life-related guidelines. Research subjects were consecutive patients discussed in EOL-CC between January 1, 2010, and September 30, 2017. The primary outcome was mortality within 6 months after the initial EOL-CC decision. Sensitivity, specificity, and diagnostic odds ratio were calculated using EOL-CC diagnosis (end-of-life or non-end-of-life) as an index test and overall survival (< 6 months or ≥ 6 months) as a reference standard.Results: In total, 315 patients were eligible for survival analysis (median age 89, range 54– 107). The study population was limited to patients with severe conditions such as advanced cancer, organ failures, advanced dementia with severe deterioration in functioning. EOL-diagnosis by our methods was associated with much lower survival rate at 6 months after EOL-CC than non-EOL-diagnosis (6.9% vs 43.5%; P < 0.001). Of the patients, 297 were eligible for diagnostic accuracy analysis (median age 89, range 54– 107). The EOL-diagnosis showed high sensitivity (0.95; 95% confidence interval [CI] 0.92– 0.97) but low specificity (0.35; 95% CI 0.20– 0.53) against the outcomes. It also showed a high diagnostic odds ratio (10.32; 95% CI 4.08– 26.13).Conclusion: The diagnostic process using the Japanese end-of-life guidelines had tolerable accuracy in identification and prognostication of end of life.Keywords: diagnostic accuracy, end-of-life, prognostication, overall survival, diagnostic odds ratio

The loss of resistance (LOR) method has been used exclusively to identify epidural space. It is difficult to find the epidural space without the risk of dural puncture. Various devices have been developed to improve the accuracy of the LOR method; however, no method has overcome the problems completely. Therefore, we devised a ligamentum flavum rupture method (LFRM) in which the needle tip is placed only on the ligamentum flavum during the epidural injection, and the injection pressure is used to rupture the ligamentum flavum and spread the drug into the epidural space. We confirmed the accuracy of this method using ultrasound with superb microvascular imaging (SMI) to visualize the epidural space. Here, we report two cases of 63-year-old and 90-year-old males. The 63-year-old patient presented with severe pain in his right buttock that extended to the posterior lower leg. The 90-year-old patient presented with intermittent claudication every 10 min. LFRM was performed, and SMI was used to confirm that the parenteral solution had spread into the epidural space. Our results indicate that LFRM can be used for interlaminar lumbar epidural steroid injections.

Study aim: To determine the difference in joint angles of the shoulder, hip, and trunk (angle of the upper torso and lower torso) during vaulting between male pole vaulters with and without chronic low back pain (LBP) and to examine the relationship between the range of motion (ROM) and maximum angle of the same joint during vaulting in all participants.

Abstract Introduction Glucose transporter 1 (GLUT1) deficiency is a rare cerebral metabolic disorder caused by the shortage of glucose supply to the brain. For this disease, ketogenic diet therapy is essential. In addition, perioperative management requires not only the continuation of ketogenic diet therapy but also the management of nausea/vomiting, diarrhea, seizures, and infection. However, there have been few reports regarding oral and maxillofacial surgery. Case presentation We describe a patient with GLUT1 deficiency who underwent orthognathic surgery. An 18-year-old man was referred to our hospital with the chief complaint of mandibular regression. Surgical tolerance was assessed by a fasting test and tooth extraction under general anesthesia, and orthognathic surgery was then performed. For orthognathic surgery, the mandibular dentition had scissor-like occlusion, and it was difficult to arrange the mandible. Therefore, we decided to perform maxillary osteotomy first. After the mandibular dentition was arranged by maxillary osteotomy, sagittal split ramus osteotomy (SSRO) was performed. Intermaxillary fixation (IMF) was necessary for SSRO, and caution was needed to prevent suffocation. The orthognathic surgery was successful, although complications, such as vomiting, diarrhea, and seizures, developed. Conclusion Surgical orthodontic treatment in GLUT1 deficiency can be performed relatively safely by maintaining the diet, taking measures against epilepsy and vomiting, and using antimicrobial agents in close collaboration with pediatricians, anesthesiologists, pharmacists, and nutritionists.

Kazuhiro Shimizu,1 Mao Takahashi,1 Shuji Sato,1 Atsuhito Saiki,1 Daiji Nagayama,1,2 Takashi Hitsumoto,3 Akira Takahara,4 Kohji Shirai1,5 1Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Chiba, Japan; 2Department of Internal Medicine, Nagayama Clinic, Oyama, Tochigi, Japan; 3Hitsumoto Medical Clinic, Shimonoseki, Yamaguchi, Japan; 4Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, Japan; 5Department of Internal Medicine, Seijinkai Mihama Hospital, Chiba, Chiba, JapanCorrespondence: Kazuhiro Shimizu, Department of Internal Medicine, Toho University Sakura Medical Center, 561-4 Shimoshizu, Sakura, Chiba, 285-8741, Japan, Tel +81-43-462-8811, Fax +81-43-462-8820, Email k432@sakura.med.toho-u.ac.jpAbstract: Predictive factors for vascular events have not been established. The vasculature of the atheroma is supplied by penetration of the vasa vasorum through the smooth muscle cell layer from the adventitia. Smooth muscle cell contraction induces compression of the vasa vasorum, resulting in ischemia in intimal atheromatous lesions. Cardio-ankle vascular index (CAVI) has become known as an index of arterial stiffness of the arterial tree from the origin of the aorta to the ankle. CAVI reflects the progress of arteriosclerosis, and a rapid rise in CAVI indicates arterial smooth muscle cell contraction. We hypothesized that rapidly increased arterial stiffness evaluated by CAVI may be a predictor of impending cardiovascular events.Keywords: arterial stiffness, stress, plaque rupture, CAVI

Masayuki Amano,1,2 Yukinori Harada,2 Taro Shimizu2 1Department of Generalist Medicine, Minaminara General Medical Center, Oyodo, Nara, Japan; 2Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Mibu, Tochigi, JapanCorrespondence: Taro Shimizu, Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, 880, Kitakobayashi, Shimotsuga, Mibu, 321-0923, Japan, Tel +81-282-86-1111, Fax +81-282-86-4775, Email shimizutaro7@gmail.comAbstract: The accumulation of optimal decision-making is vital to achieving diagnostic excellence and preventing diagnostic errors. Diagnostic uncertainty (DU) determines the difficulty of each team member’s decision-making process, including the patient, care partners, physicians, and healthcare professionals. The diagnostic approach in the low DU is already available, while the one in the high DU still needs to be clarified. In cognitive science, Sarasvathy et al established “effectuation”, a theory of decision-making under the high-uncertainty condition, by analyzing how outstanding entrepreneurs make decisions when the future is unpredictable. Based on this theory, we developed the “effectual diagnostic approach (EDA).” This simple approach allows patients and physicians to “set” problems co-creatively, emerging the outlines of the clusters of health issues under high DU conditions. After DU declines enough, the traditional problem-solving approach will help the diagnostic team achieve the patient’s well-being. EDA will offer us a guiding principle for action in the high DU. The co-creation of the “patient as an entrepreneur” with the “physician as a co-founder” will contribute to achieving diagnostic excellence.Keywords: diagnostic excellence, diagnostic uncertainty, diagnostic error, effectuation, co-creation

Carnot batteries, a type of power-to-heat-to-power energy storage, are in high demand as they can provide a stable supply of renewable energy. Latent heat storage (LHS) using alloy-based phase change materials (PCMs), which have high heat storage density and thermal conductivity, is a promising method. However, LHS requires the development of a PCM with a melting point suitable for its application. For the Carnot battery, the reuse of a conventional ultra-supercritical coal-fired power plant with a maximum operating temperature of approximately 650°C is considered. Therefore, developing a 600°C-class alloy-based PCM is crucial for realizing a highly efficient and environmentally friendly Carnot battery. Using thermodynamic calculation software (FactSage), we found that Al-5.9 mass% Si-1.6 mass% Fe undergoes a phase transformation at 576–619°C, a potential 600°C-class PCM. In this study, we investigated the practicality of an Al–Si–Fe PCM as an LHS material based on its heat storage and release properties and form stability. The examined Al–Si–Fe PCM melted until approximately 620°C with a latent heat capacity of 375–394 J·g−1. Furthermore, the PCM was found to have a thermal conductivity of approximately 160 W·m−1·K−1 in the temperature range of 100–500°C, which is significantly better than that of conventional sensible heat storage materials in terms of heat storage capacity and thermal conductivity.

Masashi Yokose, Yukinori Harada, Shogo Hanai, Shusaku Tomiyama, Taro Shimizu Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Mibu, Tochigi, 321-0293, JapanCorrespondence: Taro Shimizu, Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Kitakobayashi 880, Shimotsuga, Mibu, Tochigi, 321-0293, Japan, Tel +81 282 86-1111, Email shimizutaro7@gmail.comPurpose: The data on the diagnostic contribution of general internal medicine (GIM) consultations for undiagnosed health problems from specialists are scarce. This study aims to explore the role of generalists as diagnostic medicine consultants in tertiary care settings.Patients and Methods: We conducted a retrospective observational study at a Japanese university hospital. GIM consultations for diagnosis from other departments on outpatients aged ≧ 20 years from January 2018 to December 2020 were included. Data were extracted from electronic medical records. The primary outcome was new diagnosis rates. The secondary outcomes were new diagnosis rates with clinical significance and clinical outcomes at 90 days from the index visit.Results: A total of 328 patients were included. The top five consulting departments were orthopedics (17.0%), cardiovascular (10.3%), otorhinolaryngology (8.8%), neurology (8.8%), and gastroenterology (7.9%). GIM identified 456 chief complaints (CCs), and the top five were fever (10.9%), abnormal laboratory results (8.3%), fatigue (5.9%), and pain (7.4%) or numbness (4.6%) in the extremities. There were 139 (104/328 patients: 31.8%) specialty consultations from GIM, and the top five departments were rheumatology (21.1%), gastroenterology (19.2%), orthopedics (9.6%), psychiatry (9.6%), and neurology (9.6%). In total, 277 new diagnoses were established in 232 patients (70.7%), and 203 patients had new diagnoses with clinical significance (61.8%). Clinical outcomes at 90 days from the time of the index visit were resolution/improvement (60.7%), unchanged/worsened (22.3%), and unknown (17.0%).Conclusion: Over 70% of GIM consultations from other departments established new diagnoses with favorable outcomes in > 60% of the patients.Keywords: consultation, specialists, diagnostic error, diagnostic excellence, diagnostic uncertainty

Masahide Higo,1 Yoshio Shimizu,2,3 Keiichi Wakabayashi,2 Takehiko Nakano,1 Yasuhiko Tomino,4 Yusuke Suzuki5 1Department of Clinical Engineering, Juntendo University Shizuoka Hospital, Izunokuni, Shizuoka, Japan; 2Division of Nephrology, Department of Internal Medicine, Juntendo University Shizuoka Hospital, Izunokuni, Shizuoka, Japan; 3Shizuoka Medical Research Center for Disaster, Juntendo University, Izunokuni, Shizuoka, Japan; 4Asian Pacific Renal Research Promotion Office, Medical Corporation SHOWAKAI, Shinjuku-ku, Tokyo, Japan; 5Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, JapanCorrespondence: Yoshio Shimizu, Division of Nephrology, Department of Internal Medicine, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka, 410-2211, Japan, Tel +81-55-948-3111, Fax +81-55-946-0858, Email yosimizu@juntendo.ac.jpBackground: Although deep hypothermic circulatory arrest (DHCA) is a useful option to protect the central nervous system during aortic arch operations, the influence of simultaneous renal ischemia remains controversial.Patients and Methods: This is a retrospective observational study. Sixty-three patients who underwent thoracic aortic surgery with DHCA and 24 patients who underwent cardiac surgery without DHCA were included in this study. The mean age, preoperative serum creatinine (Cr) level, preoperative estimated glomerular filtration rate (eGFR), peak serum Cr level up to 48 hrs post-operative, elevation rate of Cr compared to the preoperative serum Cr, urine volume rate up to 48 hrs post-operative and AKI staging using the KDIGO criteria were estimated for each patient. Clinical parameters for 3 months after the operation and the 3-month post-operative mortality rate were assessed. Mean values indicating kidney function or distribution of the AKI stages were compared between patients with and without DHCA. Patients with DHCA were further divided according to the duration of ischemia to compare the values for the kidney function of each group, distribution of AKI stages and mortality.Results: The parameters indicating AKI of the patients with DHCA were significantly more severe than those without DHCA. Patients who had undergone an ischemic state for more than 40 min revealed significantly higher peak serum Cr, elevation rate of serum Cr, less urine volume up to 48 hrs post-operative compared with those without DHCA. Distribution of the AKI stages was related to the duration of ischemia. The 3-month post-operative mortality of the patients with DHCA was significantly higher than those without DHCA.Limitations: This study had limitations such as its retrospective design and small number patients, and the data will be required confirmation with other prospective studies.Conclusion: DHCA is closely related to AKI up to 48 hrs post-operative and death during the 3 months following surgery.Keywords: deep hypothermic circulatory arrest, DHCA, ischemia, acute kidney injury, AKI, KDIGO criteria

Takanobu Hirosawa, Arisa Hayashi, Yukinori Harada, Taro Shimizu Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, JapanCorrespondence: Taro Shimizu, Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu-cho, Shimotsuga, Tochigi, 321-0293, Japan, Tel + 81 282 87 2498, Fax + 81-282-87-2502, Email shimizu7@dokkyomed.ac.jpPurpose: The clinical presentation of iron deficiency is not well understood. We aimed to identify the clinical manifestations of iron deficiency without anemia in women.Patients and Methods: We conducted a retrospective cohort study of women who visited the general internal medicine outpatient department of a university hospital in Japan between 2016 and 2022. Women who were prescribed iron supplements were included in the study. Anemia was defined as hemoglobin levels below 12 g/dl. Iron deficiency was defined as serum ferritin levels < 30.0 μg/l. The primary outcome was the difference in symptoms between patients with iron deficiency with and without anemia. The secondary outcome was the ratio of symptom, hemoglobin, and serum ferritin improvement (levels > 30.0 μg/l after treatment), comparing the measurements at the beginning and after supplementation.Results: A total of 147 women were included in the final analysis. There were no significant differences in the initial symptoms and the ratio of symptom improvement between the groups. Compared to patients with iron deficiency anemia, patients with iron deficiency without anemia had high initial serum ferritin levels (14.8 vs 7.1 μg/l, p< 0.001), and hemoglobin (13.2 vs 9.9 g/dl, p< 0.001). Iron supplements significantly improved the serum ferritin level in two groups and the hemoglobin in iron deficiency anemia. After treatment, iron deficiency without anemia still had high serum ferritin levels (37.7 vs 28.2 μg/l, p=0.017) and hemoglobin (13.3 vs 12.3 g/dl, p < 0.001).Conclusion: There were no differences in any of the investigated symptoms and the ratio of the symptom improvement depending on the anemic state in iron deficiency. After iron supplementation, the serum ferritin levels in the iron deficiency without anemia group improved. Hemoglobin and serum ferritin in iron deficiency without anemia were still highly comparable to that of iron deficiency anemia.Keywords: women, hemoglobin, iron deficiency without anemia, serum ferritin

Masaki Tago,1 Risa Hirata,1 Takashi Watari,2 Kiyoshi Shikino,3 Yosuke Sasaki,4 Hiromizu Takahashi,5 Taro Shimizu6 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2General Medicine Center, Shimane University Hospital, Shimane, Japan; 3Department of General Medicine, Chiba University Hospital, Chiba, Japan; 4Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan; 5Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan; 6Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpAbstract: In Japan, general medicine is still relatively new as a specialty, having been established in 2018 as the 19th primary specialty. The relevant research field has therefore not been fully established yet, and the detailed research areas in this field have not been identified. We conducted a descriptive questionnaire-based web survey of members of the Japanese Society of Hospital General Medicine. Respondents were asked to highlight their research topics from the following categories: diagnostic excellence, design (problem-solving and thinking methodology), symptomatology, physical examination, clinical epidemiology, home and community medicine, general medicine education, organizational management, hospital administration, and “none of the above (add description of your work if desired)”. The respondents could choose multiple topics. There were 276 respondents (14% response rate), of whom 240 (86.9%) were male, 103 (37.3%) worked at universities, and 232 (84.1%) had previous research experience. Diagnostic excellence was the most common research topic category among generalists (n=87, 21.3%), followed by clinical epidemiology (n=83, 20.3%), symptomatology (n=41, 10.0%), home and community medicine (n=39, 9.6%), and general medicine education (n=36, 8.8%). Seventy-eight respondents (19.1%) chose “none of the above (add description of your work if desired)”. The main research topics were in areas fundamental to diagnostic excellence, ie, diagnostics, diagnostic error, clinical epidemiology, and symptomatology. Home and community medicine and general medicine education were also included as research topics because of their diverse roles. The research interests of generalists are therefore diverse, and new areas and frameworks are likely to be created in the future.Keywords: clinical research, diagnostic excellence, general medicine, medical education, research topic

Megumi Takahashi,1 Hiroshi Okudera,2 Masahiro Wakasugi,2 Mie Sakamoto,2 Hiromi Shimizu,3 Tokie Wakabayashi,3 Tsuneaki Yamanouchi,3 Hisashi Nagashima2 1Department of Quality and Patient Safety, Tokyo Medical University, Tokyo, Japan; 2Department of Crisis Medicine and Clinical Safety, University of Toyama, Toyama, Japan; 3Department of Medical Management Office, Toyama University Hospital, Toyama, JapanCorrespondence: Megumi Takahashi, Department of Quality and Patient Safety, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku, Tokyo, Japan, Tel +81 3 3342 6111 Ext 3939, Fax +81 3 5339 3791, Email megu3@tokyo-med.ac.jpPurpose: Our aim was to inform a new definition of wrong-patient errors, obtained through an analysis of incident reports related to medication errors.Methods: We investigated wrong-patient medication errors in incident reports voluntarily reported by medical staff using a web-based incident reporting system from 2015 to 2016 at a university hospital in Japan. Incident report content was separately evaluated by four evaluators using investigational methods for clinical incidents from the Clinical Risk Unit and the Association of Litigation and Risk Management. They investigated whether it was the patient or drug that was incorrectly chosen during wrong-patient errors in drug administration in incident reports and assessed contributory factors which affected the error occurrence. The evaluators integrated the results and interpreted them together.Results: Out of a total 4337 IRs, only 30 cases (2%) contained wrong-patient errors in medication administration. The cases where the intended drugs were administered to incorrect patients occurred less frequently than cases where the wrong drugs were administered to the intended patients through the investigation of wrong targets. After a discussion, the evaluators concluded that the patient - drug/CPOE screen mismatch, caused by choosing the wrong patient, drug, or CPOE screen (mix-ups), occurred in the wrong-patient medication errors. These errors were caused by three conditions: (1) where two patients/drugs were listed next to one another, (2) where two patients’ last names/drugs’ names were the same, and (3) where the patient/drug/CPOE screen in front of the staff involved was believed to be the correct one. Additionally, these errors also involved insufficient confirmation, which led to failure to detect and correct the mismatch occurrences.Conclusion: Based on our study, we propose a new definition of wrong-patient medication errors: they consisted of choosing a wrong target and insufficient confirmation. We will investigate other types of wrong-patient errors to apply this definition.Keywords: wrong-patient error, medication error, web-based incident reporting system, computerized physician order entry, human error

Yoshihisa Ishiura,1 Masaki Fujimura,2 Noriyuki Ohkura,3 Johsuke Hara,3 Kahori Nakahama,1 Yusuke Sawai,1 Takeshi Tamaki,1 Ryuta Murai,1 Toshiki Shimizu,1 Naoyuki Miyashita,1 Shosaku Nomura1 1First Department of Internal Medicine, Kansai Medical University, Osaka, Japan; 2Respiratory Medicine, National Hospital Organization Nanao Hospital, Nanao, Japan; 3Respiratory Medicine, Kanazawa University Hospital, Kanazawa, JapanCorrespondence: Yoshihisa Ishiura, First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan, Tel +81-6-6992-1001, Fax +81-6-6993-9837, Email ishiura-@p2322.nsk.ne.jp; ishiuray@takii.kmu.ac.jpPurpose: The ‘treatable traits’ strategy for patients with chronic inflammatory airway diseases, especially asthma and chronic obstructive pulmonary disease (COPD), is a focus of interest, because it implements precision and personalized medicine. Asthma-COPD overlap (ACO), a phenotype involving both asthma and COPD, is an important disease entity because patients with ACO have significantly worse outcomes, conferring greater economical and social burdens. Some guidelines for ACO recommend add-on therapy of long-acting muscarinic antagonists to inhaled corticosteroids and long-acting β2 agonists. However, this approach is based on extrapolation from patients with asthma or COPD alone. Consequently, a ‘treatable traits’ approach suitable for ACO remains obscure.Methods: A 12-week open-label cross-over pilot study was conducted in patients with ACO to investigate the effect of tiotropium bromide (TIO) 5 μg/day add-on therapy to fluticasone propionate/formoterol fumarate (FP/FM) 500/20 μg/day compared with FP/FM 500/20 μg/day alone. A 4-week run-in period and two 4-week treatment periods were included.Results: A total of 18 male patients with stable ACO participated in this pilot study. All patients were ex-smokers. Mean values ± standard deviation (SD) for forced expiratory volume in 1 second (FEV1) were 1.21 ± 0.49 L after the run-in period, 1.20 ± 0.51 L after the FP/FM combination therapy period, and 1.30 ± 0.48 L after the TIO add-on therapy to FP/FM period. FEV1 values after the TIO add-on therapy FP/FM period were significantly higher than those after the run-in period (p < 0.01).Conclusion: TIO add-on therapy to FP/FM in patients with ACO, considered difficult to treat because of the presence of both asthma and COPD, resulted in improvements in lung function parameters in this real-world pilot study, indicating the potential value of TIO add-on therapy as a “treatable traits” option for standard treatment for ACO.Keywords: treatable trait, asthma-COPD overlap, tiotropium, fluticasone, formoterol, triple therapy

Keita Suzuki,1 Hiromasa Tsujiguchi,1– 3 Akinori Hara,1– 3 Oanh Kim Pham,1 Sakae Miyagi,3,4 Thao Thi Thu Nguyen,5 Haruki Nakamura,1 Fumihiko Suzuki,2,6 Tomoko Kasahara,2 Yukari Shimizu,7 Yohei Yamada,2 Yasuhiro Kambayashi,8 Hirohito Tsuboi,9 Takehiro Sato,3,10 Takayuki Kannon,3,10 Kazuyoshi Hosomichi,3,10 Atsushi Tajima,3,10 Toshinari Takamura,11 Hiroyuki Nakamura1– 3 1Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 2Department of Public Health, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 3Kanazawa University Advanced Preventive Medical Sciences Research Center, Kanazawa, Ishikawa, Japan; 4Innovative Clinical Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan; 5Department of Epidemiology, Faculty of Public Health, Haiphong University of Medicine and Pharmacy, Hai Phong, Vietnam; 6Community Medicine Support Dentistry, Ohu University Hospital, Koriyama, Fukushima, Japan; 7Department of Nursing, Faculty of Health Sciences, Komatsu University, Komatsu, Ishikawa, Japan; 8Department of Public Health, Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan; 9Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 10Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 11Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, JapanCorrespondence: Keita Suzuki, Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan, Tel +81 76 265 2218, Fax +81 76 234 4233, Email ksuzuk@staff.kanazawa-u.ac.jpBackground: Previous studies examined the association between chronic pain (CP) and serum 25-hydroxyvitamin D (25(OH)D) concentrations; however, the findings obtained were inconsistent. Single nucleotide polymorphisms (SNP) associated with the transcriptional activity of the vitamin D receptor (VDR) gene may influence the association of 25(OH)D levels with CP. We aimed to clarify the association between CP, serum 25(OH)D concentration, and SNPs.Methods: In the Shika study, we performed a cross-sectional analysis of 551 participants older than 40 years who were asked whether they had been having persistent pain lasting for at least 3 months in any part of the body on a self-administered questionnaire. Serum 25(OH)D concentrations were assessed as a biomarker of the vitamin D status using a radioimmunoassay. rs731236, rs7975232, rs1544410, rs2228570, and rs11568820 were identified using peripheral blood samples, and participants were assigned to those with or without the minor allele for each SNP.Results: The prevalence of CP was 37.2%. We observed a tendency for lower 25(OH)D levels in participants with CP than in those without CP in the hetero/minor group of rs11568820, which is a polymorphism within the CDX2-binding site in the 1e promoter region of the VDR gene. Furthermore, a logistic regression analysis revealed that lower serum 25(OH)D concentrations were significantly associated with CP in the hetero/minor group, but not in the major group.Conclusion: These results suggest that sufficient serum 25(OH)D concentration reduces the risk of CP in individuals with the minor allele of the CDX2 polymorphism.Keywords: chronic pain, 25-hydroxyvitamin D, vitamin D receptor gene, promoter, polymorphism, epidemiology

"ILC Technology Network" (ITN) is an international framework for the technological development outlined in the time-critical Work Package (WP). The focus of WP1 and 2 are cavity production and cryomodule design, respectively. The High Energy Accelerator Research Organization known as KEK plans to produce one cryomodule equipped with eight superconducting 9-cell cavities for WP1 and 2 from FY2023 and conduct measurements by FY2027. To do that, a test facility will be required to perform the measurements. This test facility was named "Cryomodule Test Bunker" (CTB). The refrigerator (Linde LR280) currently operating at KEK will be used for CTB. The helium transfer line has been designed based on KEKB’s transport line design; however, it was slightly modified because the International Linear Collider (ILC) does not use liquefied nitrogen for the thermal radiation shield. It is planned to install a 2K refrigerator, a purification filter, etc. The construction of the CTB will enable us to measure the performance of the cryomodules which are the main components of the ILC. This indicates that it will be possible to verify various aspects of the fabrication and inspection of cryomodules for the ILC, and is a very important technological step towards the construction of the ILC. It can also be used as a general-purpose test stand for superconducting accelerators, which will be useful in developing future superconducting accelerators.

Eccentrically Braced Frames (EBFs) are the structural systems that are recommended to be constructed in Earthquake Hazard Areas. This system combines good characteristics in withstanding the seismic load, i.e., stiffness, ductility, and dissipation energy. Link is a component in EBFs that play the role of the seismic energy dissipator. As far, several studies have been conducted to enhance the link performance, but the information is still limited. This study observed the structural performance of the IWF flexural link, where this link will experience failure at the flange due to seismic energy dissipation. The investigation was conducted by establishing three Finite Element (FE) models of flexural link. Each link was designed with the same length, i.e. 1000 mm. Three-link models were distinguished by the differences in web stiffener configuration, i.e., non-stiffener link, 250 mmstiffener spacing link, and 100 mm-stiffener spacing link, respectively. All models were examined under cyclic loading with yield displacement controlled. The research discovered that adding the web stiffener on the IWF flexural link significantly escalated the EBFs’ seismic performance, i.e., strength, stiffness, ductility, and dissipation energy. The best seismic performance was presented by a 100 mm-stiffener spacing link. Accordingly, it is indicated that arranging the web stiffeners at the narrow space in the IWF link can be suggested to improve the seismic performance of EBFs.

Resistant structures, such as Eccentrically Braced Frames (EBFs), are required to be established in earthquake-hazard areas. In EBFs, an essential beam component, known as link, plays a crucial role in determining the performance of these structures. As the seismic energy dissipator, link experiences failure to prevent heavy damage to other EBFs members, such as beams and columns. Although several studies have been carried out to enhance the seismic performance of link, there is still limited regarding these elements. Therefore, this study aimed to investigate several IWF flexural links constructed in FE models of Inverted-V EBFs. A total of three flexural links with different stiffener spaces were considered namely non-spacing, 250 mm, and 100 mm stiffener spacing links. To assess their performance, cyclic loading with yield displacement control was used in EBFs models. Observations were mainly conducted on EBFs performances consisting of strength, stiffness, and dissipation energy. The results showed that the best seismic performance was specified on a 100 mm-stiffener spacing link by presenting the largest and most stable hysteresis curve. Based on these results, the configuration of the narrow space stiffener in the link element was recommended to improve the seismic performance of EBFs.

Astrophysical reactions involving radioactive isotopes (RI) often play an important role in high-temperature stellar environments. The experimental information on those reactions is still limited mainly due to the technical difficulties in producing high-quality and intense RI beams. Although a direct measurement of those reactions at astrophysical energy would be still challenging, we may take several alternative approaches to determine the reaction rates, by applying other mesurement methods or improving the target and detectors. Here we mainly discuss the thick-target method in inverse kinematics (TTIK) based on the successful examples of experimental studies performed at Center for Nuclear Study, the University of Tokyo, using the low-energy RI beam separator CRIB.