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.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.
3.The Association of Family and Friend Networks with Appetite: Structural Equation Modeling of the Indirect Effects of Depression among Community-Dwelling Older Adults
Kento NORITAKE ; Keisuke FUJII ; Daiki NAKASHIMA ; Yuta KUBO ; Kyosuke YOROZUYA ; Naoki TOMIYAMA ; Takahiro HAYASHI ; Fumihiko GOTO ; Hidehiro WATANABE ; Akihiro YOSHIDA
Annals of Geriatric Medicine and Research 2025;29(1):131-137
Background:
Appetite loss in older adults raises the risk of malnutrition and frailty. The recent emphasis on psychological and social support for appetite loss reveals the importance of robust social networks. Depression is linked to a decline in appetite and social networks. Social networks may influence appetite directly and indirectly through depression. This exploratory cross-sectional study categorizes social networks into family and friend networks to elucidate their direct and indirect effects.
Methods:
The study analyzed 193 community-dwelling older adults (women 78.2%; mean age 77.1±5.3 years) who participated in health-checkup events in two cities in Japan. Appetite was assessed using the Japanese version of the Simplified Nutritional Appetite Questionnaire, and family and friend networks were assessed using the Lubben Social Network Scale-6. Depression was assessed using the Geriatric Depression Scale-15. Based on previous research, we constructed a causal model examining the impacts of family and friend social networks and depression on appetite and calculated the direct and indirect effects through structural equation modeling.
Results:
The family network had a direct effect on appetite (path coefficient=0.18) and an indirect effect via depression (path coefficient=0.0608). Conversely, the friend network was not directly associated with appetite but had an indirect effect through depression (path coefficient=0.095). The model exhibited a good fit. The mechanism of influence on appetite varied between the networks.
Conclusion
To prevent appetite loss, social networks with family and friends should be assessed separately, and tailored support should be provided for each.
4.Two-year follow-up of unilateral biportal endoscopy assisted extraforaminal lumbar interbody fusion: how to perform indirect decompression and fusion under endoscopy: a retrospective study in Japan
Takaki YOSHIMIZU ; Sanshiro SAITO ; Teruaki MIYAKE ; Tetsutaro MIZUNO ; Ushio NOSAKA ; Keisuke ISHII ; Mizuki WATANABE ; Kanji SASAKI
Asian Spine Journal 2025;19(2):217-227
Methods:
Forty-nine adults who underwent single-level L4/5 interbody fusion for degenerative spondylolisthesis were divided into BE-ELIF (n=27) and OLIF (n=22) groups based on the surgical approach used. Clinical outcomes were assessed using the Visual Analog Scale and the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ). Radiographic parameters, including distance of spondylolisthesis, disc height, segmental lordosis, lumbar lordosis, pelvic tilt, and sagittal vertical axis, were evaluated preoperatively and at final follow-up.
Results:
OLIF provided significantly better relief of pain in lower limbs and buttocks at 1-year follow-up. No significant between-group differences were observed in JOABPEQ domains. BE-ELIF resulted in greater improvements in spondylolisthesis distance and disc height, while other parameters did not differ significantly between the two groups.
Conclusions
For L4/5 degenerative spondylolisthesis, BE-ELIF demonstrated superior spondylolisthesis reduction and disc height improvement than OLIF. Although BE-ELIF was associated with some inferior clinical outcomes, it provided satisfactory results, effective realignment, and a low complication risk.
5.Two-year follow-up of unilateral biportal endoscopy assisted extraforaminal lumbar interbody fusion: how to perform indirect decompression and fusion under endoscopy: a retrospective study in Japan
Takaki YOSHIMIZU ; Sanshiro SAITO ; Teruaki MIYAKE ; Tetsutaro MIZUNO ; Ushio NOSAKA ; Keisuke ISHII ; Mizuki WATANABE ; Kanji SASAKI
Asian Spine Journal 2025;19(2):217-227
Methods:
Forty-nine adults who underwent single-level L4/5 interbody fusion for degenerative spondylolisthesis were divided into BE-ELIF (n=27) and OLIF (n=22) groups based on the surgical approach used. Clinical outcomes were assessed using the Visual Analog Scale and the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ). Radiographic parameters, including distance of spondylolisthesis, disc height, segmental lordosis, lumbar lordosis, pelvic tilt, and sagittal vertical axis, were evaluated preoperatively and at final follow-up.
Results:
OLIF provided significantly better relief of pain in lower limbs and buttocks at 1-year follow-up. No significant between-group differences were observed in JOABPEQ domains. BE-ELIF resulted in greater improvements in spondylolisthesis distance and disc height, while other parameters did not differ significantly between the two groups.
Conclusions
For L4/5 degenerative spondylolisthesis, BE-ELIF demonstrated superior spondylolisthesis reduction and disc height improvement than OLIF. Although BE-ELIF was associated with some inferior clinical outcomes, it provided satisfactory results, effective realignment, and a low complication risk.
6.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.
7.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.
8.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.
9.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


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