Papers - Mikami, Yohei

Clinical outcomes of patients with remitting ulcerative colitis after discontinuation of indigo naturalis

Shimada F., Yoshimatsu Y., Sujino T., Fukuda T., Aoki Y., Hayashi Y., Tojo A., Kawaguchi T., Kiyohara H., Sugimoto S., Nanki K., Mikami Y., Miyamoto K., Takabayashi K., Hosoe N., Kato M., Ogata H., Naganuma M., Kanai T.

Scientific Reports (Scientific Reports)  14 ( 1 ) 5778 2024.12

ISSN  2045-2322

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Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.

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A CTCF-binding site in the Mdm1-Il22-Ifng locus shapes cytokine expression profiles and plays a critical role in early Th1 cell fate specification

Liu C., Nagashima H., Fernando N., Bass V., Gopalakrishnan J., Signorella S., Montgomery W., Lim A.I., Harrison O., Reich L., Yao C., Sun H.W., Brooks S.R., Jiang K., Nagarajan V., Zhao Y., Jung S., Phillips R., Mikami Y., Lareau C.A., Kanno Y., Jankovic D., Aryee M.J., Pękowska A., Belkaid Y., O'Shea J., Shih H.Y.

Immunity (Immunity)  57 ( 5 ) 1005 - 1018.e7 2024.05

ISSN  10747613

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Cytokine expression during T cell differentiation is a highly regulated process that involves long-range promoter-enhancer and CTCF-CTCF contacts at cytokine loci. Here, we investigated the impact of dynamic chromatin loop formation within the topologically associating domain (TAD) in regulating the expression of interferon gamma (IFN-γ) and interleukin-22 (IL-22); these cytokine loci are closely located in the genome and are associated with complex enhancer landscapes, which are selectively active in type 1 and type 3 lymphocytes. In situ Hi-C analyses revealed inducible TADs that insulated Ifng and Il22 enhancers during Th1 cell differentiation. Targeted deletion of a 17 bp boundary motif of these TADs imbalanced Th1- and Th17-associated immunity, both in vitro and in vivo, upon Toxoplasma gondii infection. In contrast, this boundary element was dispensable for cytokine regulation in natural killer cells. Our findings suggest that precise cytokine regulation relies on lineage- and developmental stage-specific interactions of 3D chromatin architectures and enhancer landscapes.

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Ulcerative colitis-associated neoplasms often harbor poor prognostic histologic components with low detection by biopsy

Sakakibara, R; Sugimoto, S; Takabayashi, K; Kiyohara, H; Wakisaka, Y; Kaieda, Y; Kawaida, M; Yoshimatsu, Y; Sujino, T; Hosoe, N; Kato, M; Shimoda, M; Mikami, Y; Iwao, Y; Kanai, T

INTESTINAL RESEARCH  2024.05

ISSN  1598-9100

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Efficacy of Dose Escalation of Oral 5-Aminosalicylic Acid for Ulcerative Colitis With a Mayo Endoscopic Subscore of 1: An Open Label Randomized Controlled Trial

Fukuda, T; Aoki, Y; Kiyohara, H; Yokoyama, A; Nakazawa, A; Yoshimatsu, Y; Sugimoto, S; Nanki, K; Mikami, Y; Fukuhara, K; Mizuno, S; Sujino, T; Mutaguchi, M; Takabayashi, K; Morohoshi, Y; Hosoda, Y; Ogata, H; Iwao, Y; Naganuma, M; Kanai, T

INFLAMMATORY BOWEL DISEASES  2024.04

ISSN  1078-0998

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Characteristics of flat-type ulcerative colitis-associated neoplasia on chromoendoscopic imaging with indigo carmine dye spraying

Takabayashi K., Sugimoto S., Nanki K., Yoshimatsu Y., Kiyohara H., Mikami Y., Sujino T., Kato M., Hosoe N., Shimoda M., Yahagi N., Ogata H., Iwao Y., Kanai T.

Digestive Endoscopy (Digestive Endoscopy)  36 ( 4 ) 446 - 454 2024.04

ISSN  09155635

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Objectives: Despite recent advances in endoscopic equipment and diagnostic techniques, early detection of ulcerative colitis-associated neoplasia (UCAN) remains difficult because of the complex background of the inflamed mucosa of ulcerative colitis and the morphologic diversity of the lesions. We aimed to describe the main diagnostic patterns for UCAN in our cohort, including lateral extension surrounding flat lesions. Methods: Sixty-three lesions in 61 patients with flat-type dysplasia that were imaged with dye chromoendoscopy (DCE) were included in this analysis. These DCE images were analyzed to clarify the dye-chromoendoscopic imaging characteristics of flat dysplasia, and the lesions were broadly classified into dysplastic and nondysplastic mucosal patterns. Results: Dysplastic mucosal patterns were classified into two types: small round patterns with round to roundish structures, and mesh patterns with intricate mesh-like structures. Lesions with a nondysplastic mucosal pattern were divided into two major types: a ripple-like type and a gyrus-like type. Of note, 35 lesions (55.6%) had a small round pattern, and 51 lesions (80.9%) had some type of mesh pattern. About 70% of lesions with small round patterns and 49% of lesions with mesh patterns were diagnosed as high-grade dysplasia or carcinoma, while about 30% of lesions with small round patterns and 51% of lesions with mesh patterns were diagnosed as low-grade dysplasia. Conclusion: When a characteristic mucosal pattern, such as a small round or mesh pattern, is found by DCE, the possibility of UCAN should be considered.

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Video capsule endoscopy in overt and occult obscure gastrointestinal bleeding: Insights from a single-center, observational study in Japan

Tojo A., Sujino T., Hayashi Y., Kamiya K.J.L.L., Sato M., Hinako S., Yoshimatsu Y., Kinoshita S., Kiyohara H., Mikami Y., Takabayashi K., Kato M., Ogata H., Kanai T., Hosoe N.

DEN Open (DEN Open)  4 ( 1 ) e354 2024.04

ISSN  2692-4609

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Objective: This study aimed to evaluate the use of video capsule endoscopy (VCE) in patients with obscure gastrointestinal bleeding (OGIB), compare cases of overt and occult OGIB, assess the rates of balloon-assisted enteroscopy (BAE) interventions and rebleeding, and identify predictive markers of positive VCE findings. Methods: Medical records of 430 patients who underwent VCE for OGIB between 2004 and 2022 were analyzed. Occult OGIB was defined as IDA or positive fecal occult blood, whereas overt OGIB was defined as clinically imperceptible bleeding. We retrospectively analyzed demographics, VCE findings based on Saurin classification (P0, P1, and P2), outcome of BAE interventions, and rebleeding rates. Results: A total of 253 patients with overt OGIB and 177 with occult OGIB were included. P1 findings were predominant in both groups, with a similar distribution. The percentage of patients receiving conservative therapy was higher in P1 than in P2 for both overt and occult OGIB. BAE was more frequently performed in P2 than in P1 VCE (83.0% vs. 35.3% in overt OGIB, 84.4% vs. 24.4% in occult OGIB). The percentage of positive findings and intervention in total BAE performed patients were comparable in P1 and P2 of overt OGIB, whereas these percentages in P2 were more than P1 of occult OGIB. Conclusion: VCE effectively identified OGIB lesions requiring intervention, particularly occult OGIB lesions, potentially reducing unnecessary BAE. Rebleeding rates varied according to the VCE findings, emphasizing the importance of follow-up in high-risk patients.

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Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study

Matsubara Y., Kiyohara H., Mikami Y., Nanki K., Namkoong H., Chubachi S., Tanaka H., Azekawa S., Sugimoto S., Yoshimatsu Y., Sujino T., Takabayashi K., Hosoe N., Sato T., Ishii M., Hasegawa N., Okada Y., Koike R., Kitagawa Y., Kimura A., Imoto S., Miyano S., Ogawa S., Fukunaga K., Kanai T.

Journal of gastroenterology (Journal of gastroenterology)  59 ( 3 ) 195 - 208 2024.03

ISSN  0944-1174

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BACKGROUND: Research on whether gastrointestinal symptoms correlate with the severity of Coronavirus Disease 2019 (COVID-19) has been inconclusive. This study aimed to clarify any associations between gastrointestinal symptoms and the prognosis of COVID-19. METHODS: We collected data from the Japanese nationwide registry for COVID-19 to conduct a retrospective cohort study. Data from 3498 Japanese COVID-19 patients, diagnosed at 74 facilities between February 2020 and August 2022, were analyzed in this study. Hospitalized patients were followed up until discharge or transfer to another hospital. Outpatients were observed until the end of treatment. Associations between gastrointestinal symptoms and clinical outcomes were investigated using multivariable-adjusted logistic regression models. RESULTS: The prevalence of diarrhea, nausea/vomiting, abdominal pain, and melena were 16.6% (581/3498), 8.9% (311/3498), 3.5% (121/3498), and 0.7% (23/3498), respectively. In the univariable analysis, admission to intensive care unit (ICU) and requirement for mechanical ventilation were less common in patients with diarrhea than those without (ICU, 15.7% vs. 20.6% (p = 0.006); mechanical ventilation, 7.9% vs. 11.4% (p = 0.013)). In the multivariable-adjusted analysis, diarrhea was associated with lower likelihood of ICU admission (adjusted odds ratio (aOR), 0.70; 95% confidence interval (CI), 0.53-0.92) and mechanical ventilation (aOR, 0.61; 95% CI, 0.42-0.89). Similar results were obtained in a sensitivity analysis with another logistic regression model that adjusted for 14 possible covariates with diarrhea (ICU; aOR, 0.70; 95% CI, 0.53-0.93; mechanical ventilation; aOR 0.62; 95% CI, 0.42-0.92). CONCLUSIONS: Diarrhea was associated with better clinical outcomes in COVID-19 patients.

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Proximal and Distal Bronchioles Contribute to the Pathogenesis of Non-Cystic Fibrosis Bronchiectasis

Asakura, T; Okuda, K; Chen, G; Dang, H; Kato, T; Mikami, Y; Schworer, SA; Gilmore, RC; Radicioni, G; Hawkins, P; Cardenas, SMB; Saito, M; Cawley, AM; De la Cruz, G; Chua, M; Alexis, NE; Masugi, Y; Noone, PG; Ribeiro, CMP; Kesimer, M; Olivier, KN; Hasegawa, N; Randell, SH; O'Neal, WK; Boucher, RC

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 209 ( 4 ) 374 - 389 2024.02

ISSN  1073-449X

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Post-marketing surveillance of tofacitinib in patients with ulcerative colitis in Japan: A final report of effectiveness and safety data

Matsuoka, K; Motoya, S; Yamamoto, T; Matsuura, M; Fujii, T; Shinzaki, S; Mikami, Y; Arai, S; Oshima, J; Endo, Y; Yuasa, H; Hoshi, M; Sato, K; Hisamatsu, T

JOURNAL OF CROHNS & COLITIS 18   I1407 - I1409 2024.01

ISSN  1873-9946

Clinical features and surgical necessity rate of fistulising perianal disease in newly diagnosed patients with Crohn's disease: Interim analysis of inception cohort registry study of patients with Crohn's disease (iCREST-CD)

Takatsu, N; Yamamoto, T; Nakase, H; Shinzaki, S; Watanabe, K; Fujii, T; Okamoto, R; Matsuoka, K; Yamada, A; Kunisaki, R; Matsuura, M; Shiga, H; Bamba, S; Mikami, Y; Shimoyama, T; Motoya, S; Torisu, T; Kobayashi, T; Ohmiya, N; Saruta, M; Matsuda, K; Matsumoto, T; Maemoto, A; Yoshigoe, S; Tsuchiya, H; Nishimura, R; Murata, Y; Hisamatsu, T

JOURNAL OF CROHNS & COLITIS 18   I2104 - I2106 2024.01

ISSN  1873-9946

Microbial ligand-independent regulation of lymphopoiesis by NOD1

Iwamura C., Ohnuki H., Flomerfelt F.A., Zheng L., Carletti A., Wakashin H., Mikami Y., Brooks S.R., Kanno Y., Gress R.E., Tosato G., Nakayama T., O’Shea J.J., Sher A., Jankovic D.

Nature Immunology (Nature Immunology)  24 ( 12 ) 2080 - 2090 2023.12

ISSN  15292908

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Aberrant differentiation of progenitor cells in the hematopoietic system is known to severely impact host immune responsiveness. Here we demonstrate that NOD1, a cytosolic innate sensor of bacterial peptidoglycan, also functions in murine hematopoietic cells as a major regulator of both the generation and differentiation of lymphoid progenitors as well as peripheral T lymphocyte homeostasis. We further show that NOD1 mediates these functions by facilitating STAT5 signaling downstream of hematopoietic cytokines. In steady-state, loss of NOD1 resulted in a modest but significant decrease in numbers of mature T, B and natural killer cells. During systemic protozoan infection this defect was markedly enhanced, leading to host mortality. Lack of functional NOD1 also impaired T cell-dependent anti-tumor immunity while preventing colitis. These findings reveal that, in addition to its classical role as a bacterial ligand receptor, NOD1 plays an important function in regulating adaptive immunity through interaction with a major host cytokine signaling pathway.

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Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis

Ichikawa M., Nakamoto N., Kredo-Russo S., Weinstock E., Weiner I.N., Khabra E., Ben-Ishai N., Inbar D., Kowalsman N., Mordoch R., Nicenboim J., Golembo M., Zak N., Jablonska J., Sberro-Livnat H., Navok S., Buchshtab N., Suzuki T., Miyamoto K., Teratani T., Fujimori S., Aoto Y., Konda M., Hayashi N., Chu P.S., Taniki N., Morikawa R., Kasuga R., Tabuchi T., Sugimoto S., Mikami Y., Shiota A., Bassan M., Kanai T.

Nature Communications (Nature Communications)  14 ( 1 ) 3261 2023.12

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Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles and therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers of both pathogens exhibit high disease activity and poor clinical outcomes. Colonization of PSC-derived Kp in specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses and exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets PSC-derived Kp with a sustained suppressive effect in vitro. Oral administration of the phage cocktail lowers Kp levels in Kp-colonized germ-free mice and SPF mice, without off-target dysbiosis. Furthermore, we demonstrate that oral and intravenous phage administration successfully suppresses Kp levels and attenuates liver inflammation and disease severity in hepatobiliary injury-prone SPF mice. These results collectively suggest that using a lytic phage cocktail shows promise for targeting Kp in PSC.

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Downregulation of chemokine receptor 9 facilitates CD4⁺CD8αα⁺ intraepithelial lymphocyte development

Ono K., Sujino T., Miyamoto K., Harada Y., Kojo S., Yoshimatsu Y., Tanemoto S., Koda Y., Zheng J., Sayama K., Koide T., Teratani T., Mikami Y., Takabayashi K., Nakamoto N., Hosoe N., London M., Ogata H., Mucida D., Taniuchi I., Kanai T.

Nature Communications (Nature Communications)  14 ( 1 ) 5152 2023.12

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Intestinal intraepithelial lymphocytes (IELs) reside in the gut epithelial layer, where they help in maintaining intestinal homeostasis. Peripheral CD4+ T cells can develop into CD4+CD8αα+ IELs upon arrival at the gut epithelium via the lamina propria (LP). Although this specific differentiation of T cells is well established, the mechanisms preventing it from occurring in the LP remain unclear. Here, we show that chemokine receptor 9 (CCR9) expression is low in epithelial CD4+CD8αα+ IELs, but CCR9 deficiency results in CD4+CD8αα+ over-differentiation in both the epithelium and the LP. Single-cell RNA sequencing shows an enriched precursor cell cluster for CD4+CD8αα+ IELs in Ccr9 −/− mice. CD4+ T cells isolated from the epithelium of Ccr9 −/− mice also display increased expression of Cbfβ2, and the genomic occupancy modification of Cbfβ2 expression reveals its important function in CD4+CD8αα+ differentiation. These results implicate a link between CCR9 downregulation and Cbfb2 splicing upregulation to enhance CD4+CD8αα+ IEL differentiation.

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The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis

Miyamoto K., Sujino T., Harada Y., Ashida H., Yoshimatsu Y., Yonemoto Y., Nemoto Y., Tomura M., Melhem H., Niess J.H., Suzuki T., Suzuki T., Suzuki S., Koda Y., Okamoto R., Mikami Y., Teratani T., Tanaka K., Yoshimura A., Sato T., Kanai T.

Cell Reports (Cell Reports)  42 ( 8 ) 113005 2023.08

ISSN  2211-1247

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The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities between CD4+ T cells in the spinal cord and their counterparts in the small intestine. Furthermore, we unveil a synergistic relationship between the microbiota, particularly enriched with the tryptophan metabolism gene EC:1.13.11.11, and intestinal cells. This symbiotic collaboration results in the biosynthesis of kynurenic acid (KYNA), which modulates the recruitment and aggregation of GPR35-positive macrophages. Subsequently, a robust T helper 17 (Th17) immune response is activated, ultimately triggering the onset of EAE. Conversely, modulating the KYNA-mediated GPR35 signaling in Cx3cr1+ macrophages leads to a remarkable amelioration of EAE. These findings shed light on the crucial role of microbial-derived tryptophan metabolites in regulating immune responses within extraintestinal tissues.

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Association of ulcerative colitis symptom severity and proctocolectomy with multidimensional patient-reported outcomes: a cross-sectional study

Matsuoka K., Yamazaki H., Nagahori M., Kobayashi T., Omori T., Mikami Y., Fujii T., Shinzaki S., Saruta M., Matsuura M., Yamamoto T., Motoya S., Hibi T., Watanabe M., Fernandez J., Fukuhara S., Hisamatsu T.

Journal of Gastroenterology (Journal of Gastroenterology)  58 ( 8 ) 751 - 765 2023.08

ISSN  09441174

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Background: The YOu and Ulcerative colitis: Registry and Social network (YOURS) is a large-scale, multicenter, patient-focused registry investigating the effects of lifestyle, psychological factors, and clinical practice patterns on patient-reported outcomes in patients with ulcerative colitis in Japan. In this initial cross-sectional baseline analysis, we comprehensively explored impacts of symptom severity or proctocolectomy on nine patient-reported outcomes. Methods: Patients receiving tertiary care at medical institutions were consecutively enrolled in the YOURS registry. The patients completed validated questionnaires on lifestyle, psychosocial factors, and disease-related symptoms. Severity of symptoms was classified with self-graded stool frequency and rectal bleeding scores (categories: remission, active disease [mild, moderate, severe]). The effects of symptom severity or proctocolectomy on nine scales for quality of life, fatigue, anxiety/depression, work productivity, and sleep were assessed by comparing standardized mean differences of the patient-reported outcome scores. Results: Of the 1971 survey responses analyzed, 1346 (68.3%) patients were in remission, 583 (29.6%) had active disease, and 42 (2.1%) had undergone proctocolectomy. A linear relationship between increasing symptom severity and worsening quality of life, fatigue, anxiety, depression, and work productivity was observed. Patients with even mild symptoms had worse scores than patients in remission. Patients who had undergone proctocolectomy also had worse scores than patients in remission. Conclusions: Ulcerative colitis was associated with reduced mood, quality of life, fatigue, and work productivity even in patients with mild symptoms, suggesting that management of active ulcerative colitis may improve patient-reported outcomes irrespective of disease severity. (UMIN Clinical Trials Registry: UMIN000031995, https://www.umin.ac.jp/ctr/index-j.htm).

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IL-15-producing splenic B cells play pathogenic roles in the development of autoimmune hepatitis

Fujimori S., Chu P.S., Teratani T., Harada Y., Suzuki T., Amiya T., Taniki N., Kasuga R., Mikami Y., Koda Y., Ichikawa M., Tabuchi T., Morikawa R., Yamataka K., Noguchi F., Tsujikawa H., Kurebayashi Y., Sakamoto M., Kanai T., Nakamoto N.

JHEP Reports (JHEP Reports)  5 ( 7 ) 100757 2023.07

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Background & Aims: B-cell depletion therapy with an anti-CD20 is an effective treatment strategy for patients with refractory autoimmune hepatitis (AIH). However, the mechanisms underlying B-cell action are unclear. Methods: Herein, we used the adeno-associated virus IL-12 model, in which hepatic IL-12 expression triggers liver injuries characteristic of AIH. We also analysed the clinical samples of patients with AIH. Results: B-cell depletion using anti-CD20 or splenectomy was found to improve liver functions and decrease the cytotoxic CD8+ T-cell (cytotoxic T lymphocyte [CTL]) count in the liver. This improvement was reversed by the adoptive transfer of splenic B cells derived from AAV IL-12-treated mice to splenectomised mice as it caused the hepatic CTL count to increase. RNA-sequencing analysis identified IL-15 as a key factor in pathogenic B cells, which promotes CTL expansion and subsequent migration to the liver via the CXCL9/CXCR3 axis. Indeed, IL-15 neutralisation ameliorated hepatitis by suppressing splenic and hepatic CTLs in vivo. The close distribution of B220+ B cells and CD8+ T cells in the spleen of AIH mice suggested mutual interactions. Mechanistically, IFNγ and CD40L/CD40 signalling were indispensable for the expression of IL-15 in B cells, and in vitro co-culture experiments revealed that splenic CD40L+CD8+ T cells promoted IL-15 production in B cells, which led to CTL expansion. In patients with AIH, high serum IL-15 concentration and IL-15+ B-cell counts, positively correlating with serum alanine aminotransferase levels, support translation and potential therapeutic targeting in human AIH. Conclusions: This investigation elucidated the roles of IL-15-producing splenic B cells that occur in concert with pathogenic CD8+ T cells during the development of AIH. Impact and Implications: IL-15-producing B cells were shown to exacerbate experimental AIH via cytotoxic T lymphocyte expansion. CD40L+CD8+ T cells promoted IL-15 expression in B cells, indicating the mutual interaction of both cells. High serum IL-15 concentrations, IL-15+ B-cell counts, and CD40L+IL-15Rα+CD8+ T-cell counts were confirmed in the blood of patients with AIH.

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Safety and Effectiveness of Vedolizumab in Patients with Moderate-to-Severe Ulcerative Colitis: An Interim Analysis of a Japanese Post-Marketing Surveillance Study

Matsuoka K., Hisamatsu T., Mikami Y., Yamamoto T., Motoya S., Shinzaki S., Iwakiri R., Sugiura K., Nishimura K., Kajita M., Fernandez J.L.

Advances in Therapy (Advances in Therapy)  40 ( 6 ) 2902 - 2914 2023.06

ISSN  0741238X

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Introduction: This ongoing post-marketing surveillance monitors the long-term safety and effectiveness of vedolizumab in routine clinical practice in patients with moderate-to-severe ulcerative colitis (UC) in Japan. This interim analysis assessed induction-phase data, covering the initial three doses of vedolizumab. Methods: Patients were enrolled via a web-based electronic data capture system from approximately 250 institutions. Incidence of adverse events and treatment responses were assessed by the physicians after the patient had received three doses of vedolizumab or when the drug was discontinued, whichever occurred first. Therapeutic response was defined as any treatment response, including remission or improvement of complete or partial Mayo score, and was assessed in the total and stratified patient populations according to prior tumor necrosis factor alpha (TNFα) inhibitor treatments and/or baseline partial Mayo score. Results: The total incidence of adverse drug reactions (ADRs) was 4.10% (11/268). Common ADRs were dizziness, nausea, and arthralgia, each reported in 0.75% of patients (2/268). Serious ADRs were herpes zoster oticus and UC, each reported in 0.37% of patients (1/268). Therapeutic response was reported in 84.5% (218/258) of all patients, 85.8% (127/148) of TNFα inhibitor-naïve patients, and 82.7% (91/110) of TNFα inhibitor-experienced patients. Among patients with partial Mayo score of ≥ 4 at baseline, partial Mayo score remission in patients without or with prior TNFα inhibitor treatment was 62.5% (60/96) and 45.6% (36/79), respectively. Conclusion: The results confirm a safety and effectiveness profile of vedolizumab consistent with that observed in previous trials. Clinical Trial Registration: JapicCTI-194603, NCT03824561.

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Bacteriophage therapy against pathological Klebsiella pneumoniae that determine the clinical course of primary sclerosing cholangitis

Ichikawa, M; Nakamoto, N; Kredo-Russo, S; Weinstock, E; NadavWeiner, I; Khabra, E; Ben-Ishai, N; Inbar, D; Kowalsman, N; Mordoch, R; Nicenboim, J; Golembo, M; Zak, N; Suzuki, T; Miyamoto, K; Teratani, T; Fujimori, S; Aoto, Y; Konda, M; Hayashi, N; Chu, PS; Taniki, N; Morikawa, R; Kasuga, R; Tabuchi, T; Sugimoto, S; Mikami, Y; Shiota, A; Bassan, M; Kanai, T

JOURNAL OF HEPATOLOGY 78   S409 - S409 2023.06

ISSN  0168-8278

Spatial Transcriptional Profiling of the Bronchiolectatic Lungs With Non-cystic Fibrosis Bronchiectasis (NCFB)

Asakura, T; Dang, H; Okuda, K; Chen, G; Kato, T; Mikami, Y; Gilmore, RC; Hawkins, P; Schworer, SA; Masugi, Y; Hasegawa, N; Randell, SH; O'Neal, WK; Boucher, RC

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 207 2023.05

ISSN  1073-449X

Enrichement of type I interferon signalling in the colonic ILC2 under inflammatory condition

Mikami, Y; Emi, I; Rino, I; Ichiro, M; Kanai, T

JOURNAL OF IMMUNOLOGY 210 ( 1 )  2023.05

ISSN  0022-1767

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