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NUDT15 gene variants and thiopurine-induced leukopenia in patients with inflammatory bowel disease
( Katsuyoshi Matsuoka ) 대한장연구학회 2020 Intestinal Research Vol.18 No.3
Thiopurine has been used to maintain remission and to reduce antidrug antibody formation in monoclonal antibody therapy in patients with inflammatory bowel disease (IBD). The use of thiopurine is limited by side effects such as leukopenia. Thiopurine S-methyltransferase (TPMT) variants are associated with thiopurine-induced leukopenia in Westerners, but the frequency of the risk alleles is low in Asians. Recently, a variant in the nudix hydrolase 15 (NUDT15) gene (R139C, c.415C>T) was reported to be associated with early severe leukopenia in Asians. NUDT15 is an enzyme that converts 6-thio-(deoxy)guanosine triphosphate (6-T(d)GTP) to 6-thio-(deoxy)guanosine monophosphate (6-T(d)GMTP). The R139C variant impairs the stability of the protein and increases incorporation of 6-TGTP and 6-TdGTP into RNA and DNA, respectively, resulting in leukopenia. The frequency of C/C, C/T, and T/T are approximately 80%, 20%, and 1%, respectively in East Asians. Early leukopenia occurred in less than 3% of patients with C/C and in around 20% of those with C/T, whereas it occurred in almost all patients with T/T. Patients homozygous for this variant also develop severe hair loss. The measurement of NUDT15 R139C can increase the safety of thiopurine dramatically and is a successful example of personalized medicine in the field of IBD. (Intest Res 2020;18:275-281)
Katsuyoshi Matsuoka,Kanae Togo,Noritoshi Yoshii,Masato Hoshi,Shoko Arai 대한장연구학회 2023 Intestinal Research Vol.21 No.1
Background/Aims: Patients with ulcerative colitis (UC) are at an increased risk of certain infections and malignancies compared with the general population. Incidence rates (IRs) of hospitalized infections, herpes zoster (HZ), and malignancies in patients with UC, stratified by treatment, in Japan were estimated. Methods: This retrospective study identified patients with UC treated with corticosteroids, immunosuppressants, or tumor necrosis factor inhibitors (TNFi) from 2 administrative databases (Japan Medical Data Center [JMDC] and Medical Data Vision [MDV]). IRs (unique patients with events per 100 patient‐years) were estimated for hospitalized infections, HZ, and malignancies, between June 2010 and May 2018. Results: Among 6,033 MDV patients with UC receiving corticosteroids, immunosuppressants, or TNFi, IRs (95% confidence intervals) were: hospitalized infections, 1.73 (1.52–1.93); HZ, 1.00 (0.85–1.16), and malignancies, 1.48 (1.29–1.66). Among 958 JMDC patients with UC receiving corticosteroids, immunosuppressants, or TNFi, IRs (95% confidence intervals) were: HZ, 1.82 (1.27–2.37) and malignancies, 1.35 (0.87–1.82). In both cohorts, IRs of malignancies were generally similar among patients receiving immunosuppressants, TNFi, or combination therapy (immunosuppressants and TNFi); this was also true for IRs of hospitalized infections and HZ in the MDV cohort. IRs of hospitalized infections, HZ, and malignancies were higher in patients receiving calcineurin inhibitors compared with immunosuppressants or TNFi, in both cohorts. Conclusions: IRs of hospitalized infections, HZ, and malignancies among patients with UC were generally similar regardless of UC treatment, except for calcineurin inhibitors.
Katsuyoshi Ando,Mikihiro Fujiya,Yoshiki Nomura,Yuhei Inaba,Yuuya Sugiyama,Takuya Iwama,Masami Ijiri,Keitaro Takahashi,Kazuyuki Tanaka,Aki Sakatani,Nobuhiro Ueno,Shin Kashima,Kentaro Moriichi,Yusuke Mi 대한장연구학회 2018 Intestinal Research Vol.16 No.3
Background/Aims: Venous thromboembolism (VTE) is a major extraintestinal manifestation in inflammatory bowel disease (IBD), regarded as an independent risk factor for VTE according to reports from Western countries. However, the incidence and risk factors of VTE in Asian IBD patients are not fully understood. We aimed to reveal the incidence and risk factors of VTE in Japanese IBD inpatients. Methods: The incidence of VTE in inpatients with IBD (n=340), gastrointestinal cancers (n=557), and other gastrointestinal diseases (n=569) treated at our hospital from 2009 to 2013 was retrospectively investigated. The characteristics and laboratory data of IBD inpatients with and without VTE were compared in univariate and multivariate analyses. Clinical courses of VTE in IBD were surveyed. Results: VTE was detected in 7.1% of IBD inpatients, significantly higher than in gastrointestinal cancer inpatients (2.5%) and inpatients with other gastrointestinal diseases (0.88%). The incidence of VTE in ulcerative colitis (UC) patients (16.7%) was much higher than that in those with Crohn’s disease (3.6%). In the univariate analysis, the risk factors were an older age, central venous catheter, prednisolone, surgery, low serum albumin, high serum C-reactive protein and D-dimer. According to a multivariate analysis, >50 years of age and surgery were the only risk factors. The in-hospital mortality rate of IBD inpatients with VTE was 4.2%. Conclusions: The incidence of VTE with IBD, especially UC, was found to be high compared with other digestive disease, which was almost equivalent to that of Western countries. The efficacy of prophylaxis needs to be investigated in Asian IBD patients.
Suppression of Pressure Oscillation in Supersonic Parachute Model Using a Ring
Katsuyoshi Fukiba,Yuma Ueno,Yusuke Maru 한국항공우주학회 2024 International Journal of Aeronautical and Space Sc Vol.25 No.1
A method for suppressing the pressure oscillation of supersonic parachutes is proposed in this study. This method placed a ring with a triangular or circular cross section in front of the canopy of a parachute. A rigid metal canopy was used in supersonic wind tunnel tests. Hard piano wires with a diameter of 0.8 mm were used as suspension lines and a riser to connect a fore body and the canopy. In the wind tunnel test without a ring, pressure oscillation with the accompanying time variation of the shock wave structure was observed at Mach 3.0. A detached shock wave oscillated back and forth because it interfered with the boundary layer developed on the suspension lines. A large-amplitude pressure oscillation was observed with the pressure sensor placed at the center of the canopy. The large pressure oscillation was suppressed using a ring. The time variation of the shockwave structure suppressed. The amplitude of the pressure with the sensor reduced to 1/2 of that without a ring. We also found that the location and cross-sectional shape of the ring affects the flow around the canopy.