Papers - Mikami, Yohei

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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Myeloid TLR4 signaling promotes post-injury withdrawal resolution of murine liver fibrosis

Takimoto Y., Chu P.s., Nakamoto N., Hagihara Y., Mikami Y., Miyamoto K., Morikawa R., Teratani T., Taniki N., Fujimori S., Suzuki T., Koda Y., Ishihara R., Ichikawa M., Honda A., Kanai T.

iScience (iScience)  26 ( 3 ) 106220 2023.03

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The fate of resolution of liver fibrosis after withdrawal of liver injury is still incompletely elucidated. Toll-like receptor 4 (TLR4) in tissue fibroblasts is pro-fibrogenic. After withdrawal of liver injury, we unexpectedly observed a significant delay of fibrosis resolution as TLR4 signaling was pharmacologically inhibited in vivo in two murine models. Single-cell transcriptome analysis of hepatic CD11b+ cells, main producers of matrix metalloproteinases (MMPs), revealed a prominent cluster of restorative Tlr4-expressing Ly6c2-low myeloid cells. Delayed resolution after gut sterilization suggested its microbiome-dependent nature. Enrichment of a metabolic pathway linking to a significant increase of bile salt hydrolase-possessing family Erysipelotrichaceae during resolution. Farnesoid X receptor-stimulating secondary bile acids including 7-oxo-lithocholic acids upregulated MMP12 and TLR4 in myeloid cells in vitro. Fecal material transplant in germ-free mice confirmed phenotypical correlations in vivo. These findings highlight a pro-fibrolytic role of myeloid TLR4 signaling after injury withdrawal and may provide targets for anti-fibrotic therapy.

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Network Approaches to Uncover Pathogenesis and Therapeutic Targets of Inflammatory Bowel Diseases.

Mikami Y, Kanai T

The Keio journal of medicine (Keio Journal of Medicine)  72 ( 2 ) 29 - 43 2023.03

ISSN  0022-9717

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Inflammatory bowel diseases (IBD) are currently recognized to involve chronic intestinal inflammation in genetically susceptible individuals. Patients with IBD mainly develop gastrointestinal inflammation, but it is sometimes accompanied by extraintestinal manifestations such as arthritis, erythema nodo-sum, episcleritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis. These clinical aspects imply the importance of interorgan networks in IBD. In the gastrointestinal tract, immune cells are influenced by multiple local environmental factors including microbiota, dietary environment, and intercellular networks, which further alter molecular networks in immune cells. Therefore, decipher-ing networks at interorgan, intercellular, and intracellular levels should help to obtain a comprehensive understanding of IBD. This review focuses on the intestinal immune system, which governs the physiological and pathological functions of the digestive system in harmony with the other organs. (DOI: 10.2302/kjm.2022-0015-IR; Keio J Med 72 (2): 29–43, June 2023).

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Diagnosis and Clinical Features of Perianal Lesions in Newly Diagnosed Crohn's Disease: Subgroup Analysis from Inception Cohort Registry Study of Patients with Crohn's Disease (iCREST-CD).

Yamamoto T, Nakase H, Watanabe K, Shinzaki S, Takatsu N, 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, Murata Y, Yoshigoe S, Nagasaka S, Yajima T, Hisamatsu T, iCREST-CD Study Group

Journal of Crohn's & colitis (Journal of Crohn's and Colitis)  17 ( 8 ) 1193 - 1206 2023.03

ISSN  1873-9946

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Background and Aims: Perianal lesion is a refractory phenotype of Crohn's disease [CD] with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD. Methods: Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD [iCREST-CD]. Results: Perianal lesions were present in 324 [48.2%] of 672 patients with newly diagnosed CD; 71.9% [233/324] were male. The prevalence of perianal lesions was higher in patients aged <40 years vs ≥40 years, and it decreased with age. Perianal fistula [59.9%] and abscess [30.6%] were the most common perianal lesions. In multivariate analyses, male sex, age <40 years and ileocolonic disease location were significantly associated with a high prevalence of perianal lesions, whereas stricturing behaviour and alcohol intake were associated with low prevalence. Fatigue was more frequent [33.3% vs 21.6%] while work productivity and activity impairment-work time missed [36.3% vs 29.5%] and activity impairment [51.9% vs 41.1%] were numerically higher in patients with than those without perianal lesions. Conclusions: At the time of CD diagnosis, approximately half of the patients had perianal lesions; perianal abscesses and perianal fistulas were the most common. Young age, male sex, disease location and behaviour were significantly associated with the presence of perianal lesions. The presence of perianal lesion was associated with fatigue and impairment of daily activities. Clinical trials registry: University Hospital Medical Information Network Clinical Trials Registry System [UMIN-CTR, UMIN000032237].

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Risk of venous thromboembolism with a central venous catheter in hospitalized Japanese patients with inflammatory bowel disease: a propensity score-matched cohort study

Aoki Yasuhiro, Kiyohara Hiroki, Mikami Yohei, Nanki Kosaku, Kawaguchi Takaaki, Yoshimatsu Yusuke, Sugimoto Shinya, Sujino Tomohisa, Takabayashi Kaoru, Hosoe Naoki, Ogata Haruhiko, Iwao Yasushi, Kanai Takanori

INTESTINAL RESEARCH (Intestinal Research)  21 ( 3 ) 318 - 327 2023.02

ISSN  1598-9100

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Background/Aims: Thromboprophylaxis is recommended for hospitalized patients with inflammatory bowel disease (IBD) in Western countries, although it is selectively administered to high-risk patients in East Asia. A central venous catheter (CVC) is commonly placed in patients with IBD. Although CVC placement is considered a risk factor for venous thromboembolism (VTE), the degree of increased risk in patients with IBD is uncertain. This study aimed to identify the risk of VTE with CVC placement in hospitalized Japanese patients with IBD without thromboprophylaxis. Methods: This retrospective cohort study included patients with ulcerative colitis or Crohn’s disease who were admitted for disease flares at Keio University Hospital between January 2016 and December 2020. Patients who already had thrombosis or were administered any antithrombotic treatment on admission were excluded. VTE development during the hospitalization was surveyed, and VTE risk associated with CVC indwelling was estimated using propensity score matching and inverse probability of treatment weighting analyses. Results: Altogether, 497 hospitalized patients with IBD (ulcerative colitis, 327; Crohn’s disease, 170) were enrolled. VTE developed in 9.30% (12/129) of catheterized patients and in 0.82% (3/368) of non-catheterized patients. The propensity score matching yielded 127 matched pairs of patients. The catheterized group demonstrated higher odds for VTE than the non-catheterized group (odds ratio, 13.15; 95% confidence interval, 1.68–102.70). A similar result was obtained in the inverse probability of treatment weighting analysis (odds ratio, 11.02; 95% confidence interval, 2.64–46.10). Conclusions: CVC placement is a major risk factor for VTE among hospitalized Japanese patients with IBD without thromboprophylaxis.

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Expert consensus on vaccination in patients with inflammatory bowel disease in Japan

Ishige T., Shimizu T., Watanabe K., Arai K., Kamei K., Kudo T., Kunisaki R., Tokuhara D., Naganuma M., Mizuochi T., Murashima A., Inoki Y., Iwata N., Iwama I., Koinuma S., Shimizu H., Jimbo K., Takaki Y., Takahashi S., Cho Y., Nambu R., Nishida D., Hagiwara S.i., Hikita N., Fujikawa H., Hosoi K., Hosomi S., Mikami Y., Miyoshi J., Yagi R., Yokoyama Y., Hisamatsu T.

Journal of Gastroenterology (Journal of Gastroenterology)  58 ( 2 ) 135 - 157 2023.02

ISSN  09441174

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Immunosuppressive therapies can affect the immune response to or safety of vaccination in patients with inflammatory bowel disease (IBD). The appropriateness of vaccination should be assessed prior to the initiation of IBD treatment because patients with IBD frequently undergo continuous treatment with immunosuppressive drugs. This consensus was developed to support the decision-making process regarding appropriate vaccination for pediatric and adult patients with IBD and physicians by providing critical information according to the published literature and expert consensus about vaccine-preventable diseases (VPDs) [excluding cervical cancer and coronavirus disease 2019 (COVID-19)] in Japan. This consensus includes 19 important clinical questions (CQs) on the following 4 topics: VPDs (6 CQs), live attenuated vaccines (2 CQs), inactivated vaccines (6 CQs), and vaccination for pregnancy, childbirth, and breastfeeding (5 CQs). These topics and CQs were selected under unified consensus by the members of a committee on intractable diseases with support by a Health and Labour Sciences Research Grant. Physicians should provide necessary information on VPDs to their patients with IBD and carefully manage these patients’ IBD if various risk factors for the development or worsening of VPDs are present. This consensus will facilitate informed and shared decision-making in daily IBD clinical practice.

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Non-cystic fibrosis bronchiectasis (NCFB) is a bronchiolectatic disease characterized by MUC5B-dominated mucus hyperproduction

Asakura, T; Okuda, K; Chen, G; Kato, T; Mikami, Y; Gilmore, R; Cardenas, SMB; Chua, M; Masugi, Y; Noone, P; Ribeiro, CMP; Olivier, K; Hasegawa, N; Randell, S; O'Neal, W; Boucher, R

RESPIROLOGY 28   6 - 7 2023.02

ISSN  1323-7799

Disease activity and treatment patterns of newly diagnosed adult patients with Crohn's disease in Japan: Interim analysis of inception cohort registry study of patients with Crohn's disease (iCREST-CD)

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

JOURNAL OF CROHNS & COLITIS 17   905 - 907 2023.02

ISSN  1873-9946

Dose escalation of oral 5-aminosalicylic acid for ulcerative colitis with Mayo endoscopic subscore of one improves long-term prognosis: a one-year multicentre, open-label, randomized controlled trial.

Aoki, Y; Fukuda, T; 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

JOURNAL OF CROHNS & COLITIS 17   548 - 548 2023.02

ISSN  1873-9946

Significance of 5-Aminosalicylic Acid Intolerance in the Clinical Management of Ulcerative Colitis

Mikami Y., Tsunoda J., Suzuki S., Mizushima I., Kiyohara H., Kanai T.

Digestion (Digestion)  104 ( 1 ) 58 - 65 2023.01

ISSN  00122823

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Background: Two major types of 5-aminosalicylic acid (5-ASA)-containing preparations, namely, mesalazine/5-ASA and sulfasalazine (SASP), are currently used as first-line therapy for ulcerative colitis. Recent reports show that optimization of 5-ASA therapy is beneficial for both patient outcomes and healthcare costs. Although 5-ASA and SASP have good efficacy and safety profiles, clinicians occasionally encounter patients who develop 5-ASA intolerance. Summary: The most common symptoms of acute 5-ASA intolerance syndrome are exacerbation of diarrhea, fever, and abdominal pain. Patients who discontinue 5-ASA therapy because of intolerance have a higher risk of adverse clinical outcomes, such as hospital admission, colectomy, need for advanced therapies, and loss of response to anti-tumor necrosis factor (TNF) biologics. When patients develop symptoms of 5-ASA intolerance, the clinician should consider changing the type of 5-ASA preparation. Recent genome-wide association studies and meta-analyses have shown that 5-ASA allergy is associated with certain single-nucleotide polymorphisms. Although there are no modalities or biomarkers for diagnosing 5-ASA intolerance, the drug-induced lymphocyte stimulation test can be used to assist in the diagnosis of acute 5-ASA intolerance syndrome with high specificity and low sensitivity. This review presents a general overview of 5-ASA and SASP in the treatment of inflammatory bowel disease and discusses the latest insights into 5-ASA intolerance. Key Messages: 5-ASA is used as first-line therapy for ulcerative colitis. Optimization of 5-ASA may be beneficial for patient outcomes and healthcare systems. Acute 5-ASA intolerance syndrome is characterized by diarrhea, fever, and abdominal pain. Periodic renal function monitoring is recommended for patients receiving 5-ASA.

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