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• 富山大学大学院   博士（医学）

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• ライフサイエンス   消化器内科学  

• ライフサイエンス   内科学一般  

• 人文・社会   教育学  

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• 富山大学附属病院第三内科  

• 札幌医科大学   総合診療医学講座   准教授  

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• Feasibility and reliability of the pandemic-adapted online-onsite hybrid graduation OSCE in Japan.

  Satoshi Hara, Kunio Ohta, Daisuke Aono, Toshikatsu Tamai, Makoto Kurachi, Kimikazu Sugimori, Hiroshi Mihara, Hiroshi Ichimura, Yasuhiko Yamamoto, Hideki Nomura

  Advances in health sciences education : theory and practice   29 ( 3 ) 949 - 965  2024年07月  [国際誌]

  　概要を見る

  Objective structured clinical examination (OSCE) is widely used to assess medical students' clinical skills. Virtual OSCEs were used in place of in-person OSCEs during the COVID-19 pandemic; however, their reliability is yet to be robustly analyzed. By applying generalizability (G) theory, this study aimed to evaluate the reliability of a hybrid OSCE, which admixed in-person and online methods, and gain insights into improving OSCEs' reliability. During the 2020-2021 hybrid OSCEs, one examinee, one rater, and a vinyl mannequin for physical examination participated onsite, and a standardized simulated patient (SP) for medical interviewing and another rater joined online in one virtual breakout room on an audiovisual conferencing system. G-coefficients and 95% confidence intervals of the borderline score, namely border zone (BZ), under the standard 6-station, 2-rater, and 6-item setting were calculated. G-coefficients of in-person (2017-2019) and hybrid OSCEs (2020-2021) under the standard setting were estimated to be 0.624, 0.770, 0.782, 0.759, and 0.823, respectively. The BZ scores were estimated to be 2.43-3.57, 2.55-3.45, 2.59-3.41, 2.59-3.41, and 2.51-3.49, respectively, in the score range from 1 to 6. Although hybrid OSCEs showed reliability comparable to in-person OSCEs, they need further improvement as a very high-stakes examination. In addition to increasing clinical vignettes, having more proficient online/on-demand raters and/or online SPs for medical interviews could improve the reliability of OSCEs. Reliability can also be ensured through supplementary examination and by increasing the number of online raters for a small number of students within the BZs.

  DOI PubMed

• Artificial intelligence model for analyzing colonic endoscopy images to detect changes associated with irritable bowel syndrome.

  Kazuhisa Tabata, Hiroshi Mihara, Sohachi Nanjo, Iori Motoo, Takayuki Ando, Akira Teramoto, Haruka Fujinami, Ichiro Yasuda

  PLOS digital health   2 ( 2 ) e0000058  2023年02月  [国際誌]

  　概要を見る

  IBS is not considered to be an organic disease and usually shows no abnormality on lower gastrointestinal endoscopy, although biofilm formation, dysbiosis, and histological microinflammation have recently been reported in patients with IBS. In this study, we investigated whether an artificial intelligence (AI) colorectal image model can identify minute endoscopic changes, which cannot typically be detected by human investigators, that are associated with IBS. Study subjects were identified based on electronic medical records and categorized as IBS (Group I; n = 11), IBS with predominant constipation (IBS-C; Group C; n = 12), and IBS with predominant diarrhea (IBS-D; Group D; n = 12). The study subjects had no other diseases. Colonoscopy images from IBS patients and from asymptomatic healthy subjects (Group N; n = 88) were obtained. Google Cloud Platform AutoML Vision (single-label classification) was used to construct AI image models to calculate sensitivity, specificity, predictive value, and AUC. A total of 2479, 382, 538, and 484 images were randomly selected for Groups N, I, C and D, respectively. The AUC of the model discriminating between Group N and I was 0.95. Sensitivity, specificity, positive predictive value, and negative predictive value of Group I detection were 30.8%, 97.6%, 66.7%, and 90.2%, respectively. The overall AUC of the model discriminating between Groups N, C, and D was 0.83; sensitivity, specificity, and positive predictive value of Group N were 87.5%, 46.2%, and 79.9%, respectively. Using the image AI model, colonoscopy images of IBS could be discriminated from healthy subjects at AUC 0.95. Prospective studies are needed to further validate whether this externally validated model has similar diagnostic capabilities at other facilities and whether it can be used to determine treatment efficacy.

  DOI PubMed

• Colonic TRPV4 overexpression is related to constipation severity.

  Hiroshi Mihara, Kunitoshi Uchida, Yoshiyuki Watanabe, Sohachi Nanjo, Miho Sakumura, Iori Motoo, Takayuki Ando, Masami Minemura, Jibran Sualeh Muhammad, Hiroyuki Yamamoto, Fumio Itoh, Ichiro Yasuda

  BMC gastroenterology   23 ( 1 ) 13 - 13  2023年01月  [国際誌]

  　概要を見る

  BACKGROUND: Chronic constipation is prevalent and involves both colon sensitivity and various changes in intestinal bacteria, particularly mucosa-associated microflora. Here we examined regulatory mechanisms of TRPV4 expression by co-culturing colon epithelial cell lines with intestinal bacteria and their derivatives. We also investigated TRPV4 expression in colon epithelium from patients with constipation. METHODS: Colon epithelial cell lines were co-cultured with various enterobacteria (bacterial components and supernatant), folate, LPS, or short chain fatty acids. TRPV4 expression levels and promoter DNA methylation were assessed using pyrosequencing, and microarray network analysis. For human samples, correlation coefficients were calculated and multiple regression analyses were used to examine the association between clinical background, rectal TRPV4 expression level and mucosa-associated microbiota. RESULTS: Co-culture of CCD841 cells with P. acnes, C. perfringens, or S. aureus transiently decreased TRPV4 expression but did not induce methylation. Co-culture with clinical isolates and standard strains of K. oxytoca, E. faecalis, or E. coli increased TRPV4 expression in CCD841 cells, and TRPV4 and TNF-alpha expression were increased by E. coli culture supernatants but not bacterial components. Although folate, LPS, IL-6, TNF-alpha, or SCFAs alone did not alter TRPV4 expression, TRPV4 expression following exposure to E. coli culture supernatants was inhibited by butyrate or TNF-alphaR1 inhibitor and increased by p38 inhibitor. Microarray network analysis showed activation of TNF-alpha, cytokines, and NOD signaling. TRPV4 expression was higher in constipated patients from the terminal ileum to the colorectum, and multiple regression analyses showed that low stool frequency, frequency of defecation aids, and duration were associated with TRPV4 expression. Meanwhile, incomplete defecation, time required to defecate, and number of defecation failures per 24 h were associated with increased E. faecalis frequency. CONCLUSIONS: Colon epithelium cells had increased TRPV4 expression upon co-culture with K. oxytoca, E. faecalis, or E. coli supernatants, as well as TNFα-stimulated TNFαR1 expression via a pathway other than p38. Butyrate treatment suppressed this increase. Epithelial TRPV4 expression was increased in constipated patients, suggesting that TRPV4 together with increased frequency of E. faecalis may be involved in the pathogenesis of various constipation symptoms.

  DOI PubMed

• Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer

  Takayuki Ando, Ayumu Hosokawa, Miho Sakumura, Iori Motoo, Shinya Kajiura, Katsuhisa Hirano, Takeshi Miwa, Tomotaka Yokota, Naokatsu Nakada, Yuko Ueda, Akira Ueda, Kenichiro Tsukada, Kohei Ogawa, Atsuko Nakaya, Akira Teramoto, Sohachi Nanjo, Hiroshi Mihara, Haruka Fujinami, Tsutomu Fujii, Ichiro Yasuda

  Oncology (Switzerland)   101 ( 1 ) 59 - 68  2023年01月

  　概要を見る

  Introduction: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. Methods: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. Results: The overall survival (OS) was 16.8 months (95% CI: 14.0-19.6) and 9.3 months (95% CI: 7.8-11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15-3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23-3.22), low albumin concentration (OR 2.24; 95% CI: 1.14-4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05-3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6-27.9), respectively. Conclusions: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials.

  DOI PubMed

• Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer.

  Takayuki Ando, Ayumu Hosokawa, Miho Sakumura, Iori Motoo, Shinya Kajiura, Katsuhisa Hirano, Takeshi Miwa, Tomotaka Yokota, Naokatsu Nakada, Yuko Ueda, Akira Ueda, Kenichiro Tsukada, Kohei Ogawa, Atsuko Nakaya, Akira Teramoto, Sohachi Nanjo, Hiroshi Mihara, Haruka Fujinami, Tsutomu Fujii, Ichiro Yasuda

  Oncology   101 ( 1 ) 59 - 68  2023年  [国際誌]

  　概要を見る

  INTRODUCTION: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. METHODS: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. RESULTS: The overall survival (OS) was 16.8 months (95% CI: 14.0-19.6) and 9.3 months (95% CI: 7.8-11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15-3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23-3.22), low albumin concentration (OR 2.24; 95% CI: 1.14-4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05-3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6-27.9), respectively. CONCLUSIONS: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials.

  DOI PubMed

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• うんこのつまらない話

  三原, 弘

  中外医学社  2020年01月 ISBN: 9784498140509

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• 【内科医のための臨床問題集】症例問題 消化管(Question74) 35歳女性 主訴「心窩部痛と満腹感」

  三原 弘

  Medicina ( (株)医学書院 )  61 ( 4 ) 167,176 - 167,176  2024年04月

• 【内科医のための臨床問題集】症例問題 消化管(Question73) 70歳女性 主訴「黒色便」

  三原 弘

  Medicina ( (株)医学書院 )  61 ( 4 ) 166,175 - 166,175  2024年04月

• 【患者さんからよく尋ねられる内科診療のQuestion】(第7章)消化管 [38歳女性,機能性ディスペプシア]胃もたれが続いています.内視鏡は苦手なので,薬だけ処方してもらうことはできないでしょうか?

  三原 弘

  内科 ( (株)南江堂 )  133 ( 4 ) 834 - 836  2024年04月

• 【急性腹症診療ガイドライン】急性腹症診療ガイドライン初版発刊が診療内容と被引用論文に与えた影響

  三原 弘, 前田 重信, 佐藤 格夫, 小豆畑 丈夫, 西舘 敏彦, 辻川 知之, 高山 祐一, 山田 岳史, 山岸 俊介, 佐藤 雄, 貝田 佐知子, 亀井 誠二, 関根 慎一, 井上 明星, 播摩 裕, 狩野 謙一, 和田 慎司, 近藤 浩史, 神野 敦, 井上 祐真, 藤野 紘貴, 真弓 俊彦, 吉田 雅博

  日本腹部救急医学会雑誌 ( (一社)日本腹部救急医学会 )  44 ( 3 ) 489 - 500  2024年03月

  　概要を見る

  【背景】急性腹症診療ガイドライン(以下,GL2015)評価のため普及度を調査した。【方法】(1)2014年と2022年に日本腹部救急医学会と日本プライマリ・ケア連合学会を対象にアンケート調査を実施した。(2)書籍販売数とMindsアクセス数を解析した。(3)被引用文献のレビューを行った。【結果】(1)回答者の60.9%がGL2015を認識し,64%の診療内容が変化し,周知群でより変化した。2-step methodの実践は乏しく,教育機会は不十分と回答された。2014年に比べ1ヶ所での腹部聴診,打診痛,腹壁圧痛試験,血中プロカルシトニン測定,疼痛管理,腹部大動脈破裂の転院調整が増加し,超音波検査の実施は減じた。(2)書籍は発刊月にもっとも販売され,Mindsは安定してアクセスされていた。(3)GL2015は105編で引用された。【結論】GL2015は普及し,診療行動を変化させたが,改善の必要性も示された。(著者抄録)

• 急性腹症診療ガイドライン改訂の検討 初期治療、アルゴリズム

  前田 重信, 狩野 謙一, 小豆畑 丈夫, 三原 弘, 真弓 俊彦, 吉田 雅博

  日本腹部救急医学会雑誌 ( (一社)日本腹部救急医学会 )  44 ( 2 ) 327 - 327  2024年02月

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• 便秘症根治を目指したTRPV4チャネルのメチル化異常の誘発と正常化因子の探索

  基盤研究(C)

  研究期間:

  2019年04月

  -

  2022年03月

   

  三原 弘, 内田 邦敏, 南條 宗八

  　研究概要を見る

  便秘患者では小腸から直腸にかけて伸展や微小炎症を受容するTRPV4イオンチャネルが上皮に多く発現し、便回数減少や罹患期間に関連していた。結腸上皮細胞株と細菌を培養すると、TRPV4の発現が一過性に減少するもの、不変なもの、増加するものに分けられた。発現を増加する細菌として、クレブシエラ菌、腸球菌、大腸菌が見出させ、菌体ではなく、培養成分が増加させた。短鎖脂肪酸である酪酸や、TNF-α阻害剤で発現増加が抑制された、便秘症状と便秘患者の大腸粘膜の腸球菌比率とが関連しており、酪酸産生菌を維持し、TNFα経路の抑制が慢性便秘症の予防や治療につながりうることが示唆された。

• NSAIDｓ小腸潰瘍の初期病変に関連する標的分子TRPイオンチャネル

  基盤研究(C)

  研究期間:

  2015年04月

  -

  2019年03月

   

  杉山 敏郎, 三原 弘

  　研究概要を見る

  NSAIDｓ使用の増加により、小腸潰瘍が増加している。小腸潰瘍は抗生剤投与によって抑制でき、腸内細菌あるいは代謝産物による局所炎症が重要であるが、炎症惹起因子の組織内透過に関与する分子機序は不明である。 小腸上皮細胞株を用いた研究から、NSAIDs添加後にアラキドン酸カスケード代謝産物である８，９EETが細胞内に蓄積、TRPV4の活性化を介して細胞膜透過性亢進を惹起することが判明した。NSAIDs小腸潰瘍予防にTRPV4活性化阻害効果を有する薬剤が有望であり、TRPV4活性化阻害効果を有する薬剤が選び出され、ある種の既存薬がTRPV4活性化阻害効果を有することが判明、臨床試験が計画中にある。

• 消化管上皮の内腔圧受容とATP放出機構の解明

  若手研究(B)

  研究期間:

  2014年04月

  -

  2018年03月

   

  三原 弘, 西園 啓文, 杉山 敏郎, 富永 真琴, 田渕 圭章, 渡辺 志朗, 内田 邦敏, 小泉 修一, 山脇 秀元, 鈴木 庸弘, 小澤 豊美, 藤浪 斗, 安藤 孝将, 南條 宗八

  　研究概要を見る

  国民の約15%が原因不明の慢性の腹痛を自覚し、胃腸内圧への過敏が原因の1つとされます。食道はTRPV4イオンチャネルで引っ張りを感じ、アデノシン三リン酸（ATP）輸送体（VNUT）で袋状になったATPを放出します。研究の結果、食道のみならず胃から直腸にTRPV4とVNUTがあり、引っ張りを含めたTRPV4刺激でVNUTを介してATPが放出されました。TRPV4を全身から除いたマウスは胃の動きが異常となり、ピロリ菌感染により、TRPV4が減少しました（遺伝子メチル化）。胃腸内で合成されるTRPV4活性化成分の定量化にも成功し、目に見えない腹痛を定量化できる可能性が出てきました。