Faculty Profiles - TAKAHASHI, Yoshiyuki

Papers - TAKAHASHI, Yoshiyuki

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愛知県におけるチャイルド・デス・レビュー調査から検証へ

沼口敦, 夏目淳, 齋藤伸治, 吉川哲史, 奥村彰久, 高橋義行

日本小児救急医学会雑誌 Vol. 18 ( 2 ) page： 262 - 262 2019.6

厳しい予後の告知を受け、子ども自身が終末期の意思決定を行った高校生の一例

佐々木美和, 滝良梨子, 梶山早苗, 野田弘実, 谷口理恵子, 上田一仁, 村松秀城, 高橋義行

Palliative Care Research Vol. 14 ( Suppl. ) page： S346 - S346 2019.6

Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children. Reviewed International journal Open Access

Toshihiko Okumura, Jun-Ichi Kawada, Masaharu Tanaka, Kotaro Narita, Tomonori Ishiguro, Yuji Hirayama, Sho Narahara, Genki Tsuji, Yuichiro Sugiyama, Michio Suzuki, Takeshi Tsuji, Shin Hoshino, Masahiro Nakatochi, Hideki Muramatsu, Hiroyuki Kidokoro, Yoshiyuki Takahashi, Yoshiaki Sato

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Vol. 25 ( 5 ) page： 346 - 350 2019.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) is generally a self-limiting disease, but it may become refractory. It is thought that refractory MPP is linked to the excessive immunologic responses of the host. Consequently, the use of adjunctive systemic corticosteroids may have beneficial effects. In this study, we compared the effects of high- and low-dose corticosteroid therapy in a pediatric population with refractory MPP. METHODS: We retrospectively collected data from 91 pediatric MPP patients treated with adjunctive systemic corticosteroids between April 2014 and October 2016. The patients were divided into the following two groups: high-dose corticosteroid group (2 mg/kg/day or more of prednisolone equivalents; n = 38) and low-dose corticosteroid group (<2 mg/kg/day; n = 53). Additionally, we compared the number of febrile days post-corticosteroid administration. We used 25 paired patients in a propensity score matching analysis to correct for confounding factors both by age and by days (from onset till corticosteroid therapy initiation). RESULTS: We observed that in the high-dose corticosteroid group defervescence following corticosteroid therapy initiation was achieved significantly earlier and length of hospitalization was significantly shorter (0.8 ± 1.0 vs. 1.5 ± 1.4 days and 8.2 ± 2.4 vs. 10.7 ± 2.7 days, respectively). In the propensity score matching, we observed that significant differences in the length of fever following corticosteroid therapy initiation and hospitalization were still present. Further, neither of the groups developed corticosteroid-related adverse events. CONCLUSION: Our results suggest that patients with refractory MPP treated with high-dose corticosteroid could achieve defervescence earlier and have a shorter hospitalization.

DOI： 10.1016/j.jiac.2019.01.003

Open Access

Web of Science

PubMed

High rates of ovarian function preservation after hematopoietic cell transplantation with melphalan-based reduced intensity conditioning for pediatric acute leukemia: an analysis from the Japan Association of Childhood Leukemia Study (JACLS). Reviewed

Hisanori Fujino, Hiroyuki Ishida, Akihiro Iguchi, Masaei Onuma, Koji Kato, Mariko Shimizu, Masahiro Yasui, Hiroyuki Fujisaki, Kazuko Hamamoto, Kana Washio, Hirotoshi Sakaguchi, Emiko Miyashita, Yuko Osugi, Etsuko Nakagami-Yamaguchi, Akira Hayakawa, Atsushi Sato, Yoshiyuki Takahashi, Keizo Horibe

International journal of hematology Vol. 109 ( 5 ) page： 578 - 583 2019.5

Language：English Publishing type：Research paper (scientific journal)

Women are at high risk of hypergonadotropic hypogonadism after hematopoietic cell transplantation (HCT). Hypogonadism is universal after irradiation or busulfan. We hypothesized that reduced intensity conditioning (RIC) might protect ovarian function after HCT. We retrospectively reviewed data from patients with acute leukemia treated according to the Japan Association of Childhood Leukemia Study and nationwide multicenter study protocol. We selected 11 female patients with acute leukemia who received first HCT with RIC, had survived for three or more years after HCT, and were aged ≥ 12 years at the last follow-up visit. Median age at diagnosis, HCT, and last visit were 8, 10, and 17 years. Six patients received HLA-matched bone marrow (BM), two HLA-mismatched BM, and three cord blood. Melphalan was used as conditioning regimen in all patients. At the last visit, six of seven post-pubertal patients at transplantation recovered menstruation, and four of four patients who underwent transplantation at the pre-pubertal began menstruation. Height z scores showed no significant reduction between pre-transplant and post-transplant. No patients received growth hormone treatment. Only one recipient displayed subclinical hypothyroidism. Melphalan-based RIC may be an encouraging option for patients with acute leukemia to avoid ovarian and endocrine dysfunction after HCT.

DOI： 10.1007/s12185-019-02627-9

Web of Science

PubMed

Design of a prospective multicenter randomized controlled trial evaluating the effects of gastric lavage on coffee-ground emesis in neonates: study protocol. Reviewed Open Access

Takashi Maeda, Yoshiaki Sato, Akihiro Hirakawa, Masahiro Nakatochi, Fumie Kinoshita, Takeshi Suzuki, Shintaro Ichimura, Ryoichi Ito, Ryuji Kudo, Michio Suzuki, Shin Hoshino, Yuichiro Sugiyama, Hideki Muramatsu, Hiroyuki Kidokoro, Jun-Ichi Kawada, Yoshiyuki Takahashi

Nagoya journal of medical science Vol. 81 ( 2 ) page： 227 - 232 2019.5

Language：English Publishing type：Research paper (scientific journal)

Neonates who swallow a considerable amount of maternal blood may exhibit vomiting and suckling disorder during the first few days of the postnatal period. Some clinicians treat these neonates with gastric lavage (GL) to prevent vomiting and the establishment of enteral feeding empirically, but there was no study assessing the effect of GL for neonates with coffee-ground emesis. We designed a multicenter randomized controlled trial to evaluate the efficacy and safety of GL in neonates with coffee-ground emesis. Vigorous neonates with birth weight ranging from 2500 g to 3999 g and gestational age between 37w0d and 41w6d who presented with coffee-ground emesis on more than twice and diagnosed as false melena, were divided into two groups using computerized randomization. We defined feeding intolerance (FI) as (1) ≥2 vomiting episodes in 4h or ≥3 episodes in 24h and/or (2) feeding failure on at least two occasions because of retching or poor sucking. Primary outcome is percentage of infants who present FI within 24 hours from admission. We also assessed the residual volumes, number of vomiting episodes, percentage of weight reduction at postnatal day 4, rates of body weight gain at 1 month of age, and peak serum total bilirubin value before discharge. To our knowledge, this is the first study to evaluate the safety and efficacy of GL for neonates with coffee-ground emesis. This trial is registered at UMIN Clinical Trials Registry as UMIN000026483.

DOI： 10.18999/nagjms.81.2.227

Open Access

Web of Science

PubMed

Successful hematopoietic stem cell transplantation from an HLA-mismatched parent for engraftment failure after unrelated cord blood transplantation in patients with juvenile myelomonocytic leukemia: Report of two cases. Reviewed International journal

Koshi Akahane, Atsushi Watanabe, Yoshiyuki Furuichi, Shinpei Somazu, Hiroko Oshiro, Kumiko Goi, Kazuo Sakashita, Hideki Muramatsu, Asahito Hama, Yoshiyuki Takahashi, Kenichi Koike, Seiji Kojima, Kanji Sugita, Takeshi Inukai

Pediatric transplantation Vol. 23 ( 3 ) page： e13378 2019.5

Language：English Publishing type：Research paper (scientific journal)

JMML is an aggressive hematopoietic malignancy of early childhood, and allogeneic HSCT is the only curative treatment for this disease. Umbilical cord blood is one of donor sources for HSCT in JMML patients who do not have an HLA-compatible relative, but engraftment failure remains a major problem. Here, we report two cases of JMML who were successfully rescued by HSCT from an HLA-mismatched parent after development of primary engraftment failure following unrelated CBT. Both patients had severe splenomegaly and underwent unrelated CBT from an HLA-mismatched donor. Immediately after diagnosis of engraftment failure, both patients underwent HSCT from their parent. For the second HSCT, we used RIC regimens consisting of FLU, CY, and a low dose of rabbit ATG with or without TBI and additionally administered ETP considering their persistent severe splenomegaly. Both patients achieved engraftment without severe treatment-related adverse effects. After engraftment of second HSCT, their splenomegaly was rapidly regressed, and both patients showed no sign of relapse for over 4 years. These observations demonstrate that HSCT from an HLA-mismatched parent could be a feasible salvage treatment for primary engraftment failure in JMML patients.

DOI： 10.1111/petr.13378

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PubMed

難治性マイコプラズマ肺炎に対するステロイド療法の検討

奥村俊彦, 川田潤一, 田中雅大, 成田幸太郎, 石黒智紀, 平山祐司, 楢原翔, 辻元基, 松村秀城, 城所博之, 佐藤義朗, 高橋義行, 杉山裕一朗, 鈴木道雄, 辻健史, 星野伸

日本小児科学会雑誌 Vol. 123 ( 5 ) page： 912 - 913 2019.5

左頸部の軟属腫様皮疹から診断した多臓器型Langerhans cell histiocytosis(LCH)の1例

太田早紀, 桃原真理子, 河野通浩, 秋山真志, 北澤宏展, 高橋義行

日本皮膚科学会雑誌 Vol. 129 ( 6 ) page： 1360 - 1360 2019.5

小児血液・腫瘍医からみた血液・がん疾患に関連する皮膚病変

川島希, 高橋義行

日本皮膚科学会雑誌 Vol. 129 ( 5 ) page： 1069 - 1069 2019.5

非ウイルスベクター法を用いたキメラ抗原受容体遺伝子導入T細胞(CAR-T細胞)療法の現状と展望

高橋義行

日本医学会総会会誌 Vol. 30回 page： LS - 1 2019.4

可能な限り鎮静を減らすために 4歳児が鎮静なく放射線治療ができた関わり

村嶋一歩, 佐々木美和, 野田弘実, 高橋義行

日本小児血液・がん学会雑誌 Vol. 56 ( 1 ) page： 74 - 74 2019.4

友達の死を他の患児へ伝え、グリーフケアにつなげる取り組み

牧田夏美, 佐々木美和, 萩原沙織, 和田拓哉, 森本綾, 西川英里, 高橋義行, 柴田有理, 河野智子

日本小児血液・がん学会雑誌 Vol. 56 ( 1 ) page： 74 - 75 2019.4

Discontinuation of L-asparaginase and poor response to prednisolone are associated with poor outcome of ETV6-RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia. Reviewed

Usami I, Imamura T, Takahashi Y, Suenobu SI, Hasegawa D, Hashii Y, Deguchi T, Hori T, Shimada A, Kato K, Ito E, Moriya-Saito A, Kawasaki H, Hori H, Yumura-Yagi K, Hara J, Sato A, Horibe K, Japan, Association of Childhood Leukemia Study Group (JACLS

International journal of hematology Vol. 109 ( 4 ) page： 477 - 482 2019.4

Language：English Publishing type：Research paper (scientific journal)

ETV6-RUNX1-positive B precursor acute lymphoblastic leukemia (B-ALL) is a common subtype of pediatric B-ALL that has shown excellent outcomes in contemporary clinical trials for pediatric B-ALL. Examinations of the possibility of reducing therapeutic intensity may thus be explored. This prospective study examined outcomes in 205 pediatric patients with ETV6-RUNX1-positive B-ALL uniformly treated following the Japan Association of Childhood Leukemia Study Group (JACLS) ALL-02 protocol. The JACLS ALL-02 protocol does not employ minimal residual disease detected by polymerase chain reaction (PCR-MRD)-based risk stratification; however, 4-year event-free survival (EFS) and overall survival (OS) were 94.4 ± 1.6 and 97.5 ± 1.1%, respectively. In particular, 92 of 205 (44.9%) patients were successfully treated with a less intensive regimen involving only two cycles of high dose methotrexate and one course of re-induction therapy comprising vincristine, L-asparaginase (L-asp), pirarubicin, and prednisolone. Multivariate analysis revealed that discontinuation of L-asp and poor response to prednisolone was, respectively, associated with poor EFS (HR 6.3; 95% CI 1.3-27.0) and OS (HR 17.5; 95% CI 2.3-130), suggesting that the majority of ETV6-RUNX1-positive B-ALL cases may be cured by a less-intensive chemotherapy regimen if the risk stratification system including PCR-MRD monitoring and insufficient use of L-asp is avoided.

DOI： 10.1007/s12185-019-02599-w

PubMed

AYA世代を迎えた小児血液疾患・腫瘍疾患経験者の患者会の発足と活動報告

太田晃嗣, 佐々木美和, 清水直子, 秋田麻衣, 谷口理恵子, 西川英里, 高橋義行

日本小児血液・がん学会雑誌 Vol. 56 ( 1 ) page： 73 - 73 2019.4

A combination of serum anti-<i>Helicobacter pylori</i> antibody titer and Kyoto classification score could provide a more accurate diagnosis of <i>H pylori</i>. Reviewed International journal Open Access

Nishizawa T, Sakitani K, Suzuki H, Yamakawa T, Takahashi Y, Yamamichi N, Watanabe H, Seto Y, Koike K, Toyoshima O

United European gastroenterology journal Vol. 7 ( 3 ) page： 343 - 348 2019.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: We previously showed that the endoscopic Kyoto classification for gastritis could predict Helicobacter pylori infection in individuals with a high negative titer of serum anti-H pylori antibodies. This study evaluated H pylori infection and the Kyoto classification score in patients with a low negative titer (<3 U/ml), high negative titer (3-9.9 U/ml), low positive titer (10-49.9 U/ml), and high positive titer (≥50 U/ml). METHODS: Serum antibody levels, Kyoto classification score and histology were investigated in 870 individuals with no history of H pylori-eradication therapy. Urea breath tests (UBTs) were additionally conducted for patients with a low negative titer and a Kyoto score ≥1 or an antibody titer ≥10 U/ml and a Kyoto score of 0 or 1. UBTs and/or histological studies were conducted for participants with a high negative titer. RESULTS: False diagnoses based on anti-H pylori antibody titers were observed in 0.3% of the low-negative-titer group, 11.7% of the high-negative-titer group, 18.9% of the low-positive-titer group and 2.2% of the high-positive-titer group. Surprisingly, false diagnoses based on antibody titers were noted in 63.2% of patients with a low positive titer and a Kyoto score of 0 and in 62.5% of patients with a high negative titer and a Kyoto score ≥2, respectively. CONCLUSIONS: Endoscopic findings could predict false diagnoses determined using serum antibody titers.

DOI： 10.1177/2050640619825947

Open Access

PubMed

Defective Epstein-Barr virus in chronic active infection and haematological malignancy. Reviewed International journal

Yusuke Okuno, Takayuki Murata, Yoshitaka Sato, Hideki Muramatsu, Yoshinori Ito, Takahiro Watanabe, Tatsuya Okuno, Norihiro Murakami, Kenichi Yoshida, Akihisa Sawada, Masami Inoue, Keisei Kawa, Masao Seto, Koichi Ohshima, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Yohei Narita, Masahiro Yoshida, Fumi Goshima, Jun-Ichi Kawada, Tetsuya Nishida, Hitoshi Kiyoi, Seiichi Kato, Shigeo Nakamura, Satoko Morishima, Tetsushi Yoshikawa, Shigeyoshi Fujiwara, Norio Shimizu, Yasushi Isobe, Masaaki Noguchi, Atsushi Kikuta, Keiji Iwatsuki, Yoshiyuki Takahashi, Seiji Kojima, Seishi Ogawa, Hiroshi Kimura

Nature microbiology Vol. 4 ( 3 ) page： 404 - 413 2019.3

Language：English Publishing type：Research paper (scientific journal)

Epstein-Barr virus (EBV) infection is highly prevalent in humans and is implicated in various diseases, including cancer1,2. Chronic active EBV infection (CAEBV) is an intractable disease classified as a lymphoproliferative disorder in the 2016 World Health Organization lymphoma classification1,2. CAEBV is characterized by EBV-infected T/natural killer (NK) cells and recurrent/persistent infectious mononucleosis-like symptoms3. Here, we show that CAEBV originates from an EBV-infected lymphoid progenitor that acquires DDX3X and other mutations, causing clonal evolution comprising multiple cell lineages. Conspicuously, the EBV genome in CAEBV patients harboured frequent intragenic deletions (27/77) that were also common in various EBV-associated neoplastic disorders (28/61), including extranodal NK/T-cell lymphoma and EBV-positive diffuse large B-cell lymphoma, but were not detected in infectious mononucleosis or post-transplant lymphoproliferative disorders (0/47), which suggests a unique role of these mutations in neoplastic proliferation of EBV-infected cells. These deletions frequently affected BamHI A rightward transcript microRNA clusters (31 cases) and several genes that are essential for producing viral particles (20 cases). The deletions observed in our study are thought to reactivate the lytic cycle by upregulating the expression of two immediate early genes, BZLF1 and BRLF14-7, while averting viral production and subsequent cell lysis. In fact, the deletion of one of the essential genes, BALF5, resulted in upregulation of the lytic cycle and the promotion of lymphomagenesis in a xenograft model. Our findings highlight a pathogenic link between intragenic EBV deletions and EBV-associated neoplastic proliferations.

DOI： 10.1038/s41564-018-0334-0

Web of Science

PubMed

Publisher Correction: Defective Epstein-Barr virus in chronic active infection and haematological malignancy. Reviewed International journal Open Access

Nature microbiology Vol. 4 ( 3 ) page： 544 - 544 2019.3

Language：English Publishing type：Research paper (scientific journal)

In the version of this Letter originally published, in the sentence beginning "The major driver role of DDX3X mutations...", the citation "Fig. 2a-f" should have been "Fig. 2". In addition, in the sentence beginning "Another finding of interest was the presence of identical driver mutations...", the citation "Fig. 3a,b and Fig. 4" should have been "Fig. 3". This has now been amended in all versions of the Letter.

DOI： 10.1038/s41564-019-0387-8

PubMed

次世代シークエンス解析による発熱性好中球減少症の網羅的病原微生物検出

堀場千尋, 鳥居ゆか, 鈴木高子, 武内俊, 奥村俊彦, 川田潤一, 伊藤嘉規, 高橋義行, 嶋田繭子, 荻朋男

感染症学雑誌 Vol. 93 ( 臨増 ) page： 325 - 325 2019.3

がん診療拠点病院における整形外科 -その現状と課題- 小児がん拠点病院における整形外科診療小児がん治療後の整形外科的問題点と小児期の骨・軟部肉腫

西田佳弘, 内田広夫, 高橋義行, 石黒直樹

日本整形外科学会雑誌 Vol. 93 ( 2 ) page： S371 - S371 2019.3

Frequent intragenic microdeletions of elastin in familial supravalvular aortic stenosis. Reviewed International journal

Satoshi Hayano, Yusuke Okuno, Makiko Tsutsumi, Hidehito Inagaki, Yoshie Fukasawa, Hiroki Kurahashi, Seiji Kojima, Yoshiyuki Takahashi, Taichi Kato

International journal of cardiology Vol. 274 page： 290 - 295 2019.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Supravalvular aortic stenosis (SVAS) is a congenital heart disease affecting approximately 1:25,000 live births. SVAS may occur sporadically, be inherited in an autosomal dominant manner, or be associated with Williams-Beuren syndrome, a complex developmental disorder caused by a microdeletion of chromosome 7q11.23. ELN on 7q11.23, which encodes elastin, is the only known gene to be recurrently mutated in less than half of SVAS patients. METHODS: Whole-exome sequencing (WES) was performed for seven familial SVAS families to identify other causative gene mutations of SVAS. RESULTS: Three truncating mutations and three intragenic deletions affecting ELN were identified, yielding a diagnostic efficiency of 6/7 (85%). The deletions, which explained 3/7 of the present cohort, spanned 1-29 exons, which might be missed in the course of mutational analysis targeting point mutations. The presence of such deletions was validated by both WES-based copy number estimation and multiplex ligation-dependent probe amplification analyses, and their pathogenicity was reinforced by co-segregation with clinical presentations. CONCLUSIONS: The majority of familial SVAS patients appear to carry ELN mutations, which strongly indicates that elastin is the most important causative gene for SVAS. The frequency of intragenic deletions highlights the need for quantitative tests to analyze ELN for efficient genetic diagnosis of SVAS.

DOI： 10.1016/j.ijcard.2018.09.032

Web of Science

PubMed

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Papers - TAKAHASHI, Yoshiyuki