1.Gut Microbiota Involved in the Immunopathogenesis of Autoimmune Pancreatitis
Kosuke MINAGA ; Tomohiro WATANABE ; Akane HARA ; Tomoe YOSHIKAWA ; Ken KAMATA ; Masatoshi KUDO
Gut and Liver 2025;19(2):171-176
Autoimmune pancreatitis (AIP), which is considered the pancreatic expression of a systemic immunoglobulin G4-related disease, is characterized by excessive infiltration of plasmacytes bearing immunoglobulin G4 and a unique form of fibrosis in multiple organs. This relatively new disease entity has garnered great attention from clinicians, but its pathophysiology remains poorly understood. Recent discoveries indicate that plasmacytoid dendritic cell activation followed by robust production of type I interferon and interleukin-33 plays a key role in driving chronic fibro-inflammatory responses in both murine and human AIP. Furthermore, the compositional alterations in the gut microbiota, known as intestinal dysbiosis, triggered plasmacytoid dendritic cell-driven pathogenic type I interferon responses. Intestinal dysbiosis is associated with a breakdown in intestinal barrier function; thus, we examined whether the latter condition affects the development of experimental AIP. Our recent research has revealed that intestinal barrier disruption worsens experimental AIP by facilitating the translocation of pathogenic bacteria, such as Staphylococcus sciuri, to the pancreas from the gut. These results indicate the “gut-pancreas axis” underlies the immunopathogenesis of AIP, and the maintenance of intestinal barrier integrity can prevent the worsening of AIP by inhibiting pancreatic colonization by harmful gut bacteria. In this mini review, the interactions between AIP development and gut microbiota are discussed with the aim of providing useful information not only for researchers but also for clinicians.
2.Revision surgery for malocclusion after open reduction of mandibular fracture: a case report
Takuma WATANABE ; Makoto HIROTA
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2025;51(1):54-58
Insufficient treatment of mandibular fractures can result in malocclusion, often necessitating revision surgery. Therefore, appropriate surgical treatment by oral and maxillofacial surgeons with adequate consideration of the occlusion is crucial. Moreover, in patients with bone defects between the fractured ends, bone grafting may be required. A 48-year-old man was referred to our department with malocclusion after initial surgery for mandibular fracture performed by plastic surgeons at another hospital. We performed revision surgery with bone grafting for a bone defect, and favorable postoperative occlusion and bone healing were achieved. Occlusal reconstruction is paramount, and bone grafting may be required if the procedure creates a bone defect. The skills and technique of oral and maxillofacial surgeons are critical, although collaboration with plastic surgeons may be necessary.
3.Gut Microbiota Involved in the Immunopathogenesis of Autoimmune Pancreatitis
Kosuke MINAGA ; Tomohiro WATANABE ; Akane HARA ; Tomoe YOSHIKAWA ; Ken KAMATA ; Masatoshi KUDO
Gut and Liver 2025;19(2):171-176
Autoimmune pancreatitis (AIP), which is considered the pancreatic expression of a systemic immunoglobulin G4-related disease, is characterized by excessive infiltration of plasmacytes bearing immunoglobulin G4 and a unique form of fibrosis in multiple organs. This relatively new disease entity has garnered great attention from clinicians, but its pathophysiology remains poorly understood. Recent discoveries indicate that plasmacytoid dendritic cell activation followed by robust production of type I interferon and interleukin-33 plays a key role in driving chronic fibro-inflammatory responses in both murine and human AIP. Furthermore, the compositional alterations in the gut microbiota, known as intestinal dysbiosis, triggered plasmacytoid dendritic cell-driven pathogenic type I interferon responses. Intestinal dysbiosis is associated with a breakdown in intestinal barrier function; thus, we examined whether the latter condition affects the development of experimental AIP. Our recent research has revealed that intestinal barrier disruption worsens experimental AIP by facilitating the translocation of pathogenic bacteria, such as Staphylococcus sciuri, to the pancreas from the gut. These results indicate the “gut-pancreas axis” underlies the immunopathogenesis of AIP, and the maintenance of intestinal barrier integrity can prevent the worsening of AIP by inhibiting pancreatic colonization by harmful gut bacteria. In this mini review, the interactions between AIP development and gut microbiota are discussed with the aim of providing useful information not only for researchers but also for clinicians.
4.Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya NISHIOKA ; Tae HATA ; Tadaaki YAMADA ; Yasuhiro GOTO ; Akihiko AMANO ; Yoshiki NEGI ; Satoshi WATANABE ; Naoki FURUYA ; Tomohiro OBA ; Tatsuki IKOMA ; Akira NAKAO ; Keiko TANIMURA ; Hirokazu TANIGUCHI ; Akihiro YOSHIMURA ; Tomoya FUKUI ; Daiki MURATA ; Kyoichi KAIRA ; Shinsuke SHIOTSU ; Makoto HIBINO ; Asuka OKADA ; Yusuke CHIHARA ; Hayato KAWACHI ; Takashi KIJIMA ; Koichi TAKAYAMA
Cancer Research and Treatment 2025;57(2):412-421
Purpose:
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods:
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results:
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
5.Daily quercetin supplementation alters motor unit behavior and enhances muscle strength adaptation in response to resistance training in older adults
Taichi NISHIKAWA ; Ryosuke TAKEDA ; Saeko UEDA ; Kaito IGAWA ; Tetsuya HIRONO ; Masamichi OKUDAIRA ; Yukiko MITA ; Toshiyuki OHYA ; Kohei WATANABE
Japanese Journal of Physical Fitness and Sports Medicine 2025;74(1):101-101
7.A Case of Afebrile Incomplete Kawasaki Disease With Coronary Artery Dilatation
Yohei SHIMOTSU ; Yuko NAKAMURA ; Tomohiro WATANABE ; Seiichi WATANABE
Journal of the Japanese Association of Rural Medicine 2025;73(5):461-466
Fever is a major symptom of Kawasaki disease, occurring in 99.5% of patients. We report a case of coronary artery aneurysms without fever in an 8-month-old male infant, who was referred to our department on the 8th day of illness for evaluation of red eyes and erythema at the BCG vaccination site. On the 16th day of illness, he was referred again to our department with membranous debris on his fingers. Cardiac ultrasonography revealed coronary artery aneurysms (#1, 3.9mm [Z=6.68]; #5, 3.3mm [Z=4.96]), and we diagnosed incomplete Kawasaki disease. Coronary angiography performed at the age of 1 year (3 months after disease onset) showed regression of coronary artery aneurysms #1 and #5 to 2.1mm (Z=2.12) and 2.1mm (Z=1.33), respectively; therefore, administration of anticoagulants and antiplatelet agents was discontinued. Considering the possibility of incomplete Kawasaki disease, comprehensive evaluation of coronary artery lesions is warranted even in afebrile patients who present with red eyes and erythema at the site of the BCG inoculation.
8.Towards the Integration of Positive Deviance Approach and Logical Framework Approach in the Field of International Development
Keiko KITA ; Kenzo TAKAHASHI ; Koichiro WATANABE
Journal of International Health 2025;40(1):29-39
Positive Deviance (PD) is based on the observation that in every community there are certain individuals or groups whose uncommon behaviors and strategies enable them to find better solutions to problems than their peers, while having access to the same resources and facing similar or worse challenges. Developed in 1990 by Save the Children to improve child nutrition in Vietnam, the PD approach has gained traction among development partners for various international development projects. This paper discusses how the PD approach and the Logical Framework Approach can be integrated in global health projects. The PD approach is effective for projects targeting behavior change, such as those aiming to improve nutrition, reduce infant mortality, promote reproductive health, and prevent non-communicable diseases. To integrate PD with the Logical Framework Approach, projects should create a logic model outlining inputs, activities, outputs, outcomes, and impacts. The PD approach should then be incorporated into each stage of this model. An objective that should be achieved through behavior change is defined as Outcome (Project Purpose), and Outputs need to be considered with the governance and the structure of the target societies and organizations as determinant factors for the dissemination of PD practices. Five steps of the PD implementation process, i.e., defining problems, identifying positive deviants, specifying and extracting PD practices, planning and implementing activities, and monitoring and evaluating, can be incorporated in the project as activities. Inputs should emphasize local initiatives, with experts playing supportive roles. While an increasing number of development partners for low- and middle-income countries have adopted the PD approach, such initiatives are still rare among Japanese organizations. The case presented demonstrates that even small-scale projects can yield significant results, encouraging Japanese colleagues to learn from this experience and consider how to initiate the challenge of applying the PD approach in future projects.
10.Progress of Core Flexibility and Core Muscle Strength in Fresh Lumbar Spondylolysis
Ryo HIMI ; Tetsuya ISHIKAWA ; Takaya SUGIYAMA ; Hidetoshi MIYAKE ; Kazuma WATANABE
The Japanese Journal of Rehabilitation Medicine 2025;():23047-
Objective: To clarify the progression of core flexibility and core muscle strength in fresh lumbar spondylolysis before and after the introduction of rehabilitation treatment. Methods: We enrolled 160 patients diagnosed with fresh lumbar spondylolysis based on magnetic resonance imaging findings from September 2019 to December 2022. Posterior Lumbar Flexibility test and Lumbar Locked Rotation test were performed to assess core flexibility. The Kraus-Weber test and Sahrmann Core Stability test were performed to assess core muscle strength. The initial and final evaluations of all tests were compared.Results: All tests showed significant improvement at the final evaluation compared to the initial evaluation.Conclusion: Patients with lumbar spondylolysis often had decreased core flexibility and core muscle strength at the initial evaluation; these parameters improved at the final evaluation owing to rehabilitation treatment.


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