Faculty Profiles - TAKAHASHI, Yoshiyuki

Novel mutation in KIF23 causing congenital dyserythropoietic anemia type III in patients who underwent allogeneic hematopoietic stem cell transplantation

Increased response to granulocyte-macrophage colony-stimulating factor in peripheral blood cells and transient manifestations mimicking juvenile myelomonocytic leukemia in a male patient with NEMO deficiency caused by a deep intronic pathogenic variant of IKBKG. Open Access

Ueki M, Hirabayashi S, Honda Y, Takezaki S, Ohata H, Abdrabou SSMA, Sawai S, Terashita Y, Cho Y, Muramatsu H, Izawa K, Yasumi T, Takahashi Y, Yamada M, Manabe A

Immunological medicine Vol. 48 ( 1 ) page： 94 - 101 2025.3

Successful Treatment with Sirolimus of a Patient with a Novel CARD11 Germline Mutation in B-Cell Expansion with Nuclear Factor Kappa B and T-Cell Anergy: Case Report and Literature Review. Open Access

Nishinosono T, Muramatsu H, Wakamatsu M, Yamashita D, Fukasawa T, Shirakawa Y, Sajiki D, Maemura R, Tsumura Y, Yamamori A, Narita K, Kataoka S, Narita A, Nishio N, Miyajima Y, Takahashi Y

Journal of clinical immunology Vol. 45 ( 1 ) page： 78 2025.2

Application of simple preparation for pediatric magnetic resonance imaging: a multicenter study in Japan.

Sawada N, Kawada JI, Kito S, Takeo T, Narita H, Fukushima M, Masuda Y, Mitsumatsu T, Kawano Y, Sakaguchi Y, Nishio N, Kidokoro H, Sato Y, Takahashi Y, Nagoya Collaborative Clinical Research Team

Pediatric radiology 2025.2

Nanoscale visualization of the anti-tumor effect of a plasma-activated Ringer's lactate solution. Open Access

Usuda J, Yagyu K, Tanaka H, Hori M, Ishikawa K, Takahashi Y

Faraday discussions Vol. 257 ( 0 ) page： 212 - 223 2025.2

Motor and functional characteristics in school-age survivors of congenital diaphragmatic hernia: a cross-sectional observational study.

Mitsumatsu T, Ito Y, Muramatsu Y, Sato Y, Ito T, Narahara S, Miura R, Yamamoto H, Ito M, Shiraki A, Nakata T, Kotani T, Natsume J, Hayakawa M, Takahashi Y, Kidokoro H

Archives of disease in childhood. Fetal and neonatal edition 2025.2

Surgical strategy for metastatic spinal tumors based on Spine Instability Neoplastic Score and patient-reported outcomes: JASA multicenter prospective study. Open Access

Nakajima H, Watanabe S, Honjoh K, Kubota A, Shiratani Y, Suzuki A, Terai H, Shimizu T, Kakutani K, Kanda Y, Tominaga H, Kawamura I, Ishihara M, Paku M, Takahashi Y, Funayama T, Miura K, Shirasawa E, Inoue H, Kimura A, Iimura T, Moridaira H, Akeda K, Takegami N, Nakanishi K, Sawada H, Matsumoto K, Funaba M, Suzuki H, Funao H, Oshigiri T, Hirai T, Otsuki B, Kobayakawa K, Uotani K, Manabe H, Tanishima S, Hashimoto K, Iwai C, Yamabe D, Hiyama A, Seki S, Goto Y, Miyazaki M, Watanabe K, Nakamae T, Kaito T, Nakashima H, Nagoshi N, Kato S, Imagama S, Watanabe K, Inoue G, Furuya T

Journal of neurosurgery. Spine Vol. 42 ( 2 ) page： 203 - 214 2025.2

Real-world Outcomes of Commercial Tisagenlecleucel for Children, Adolescents, and Young Adults With Acute Lymphoblastic Leukemia in Japan. Open Access

Kato I, Tomizawa D, Kato M, Hirabayashi S, Manabe A, Irie M, Sasahara Y, Arakawa Y, Koh K, Sakaguchi H, Sugiyama M, Ogawa C, Kamiya T, Saito S, Nakazawa Y, Nishio N, Takahashi Y, Iwai N, Adachi S, Takita J, Miyamura T, Yokoyama S, Oba U, Ueda T, Koga Y, Hiramatsu H

Transplantation and cellular therapy Vol. 31 ( 2 ) page： 86 - 96 2025.2

Mechanical signaling through membrane tension induces somal translocation during neuronal migration. Open Access

Minegishi T, Hasebe H, Aoyama T, Naruse K, Takahashi Y, Inagaki N

The EMBO journal Vol. 44 ( 3 ) page： 767 - 780 2025.2

Cord Blood Transplantation Using Myeloablative Conditioning for Pediatric Advanced Myelodysplastic Syndrome in AMeD Syndrome With a Novel ADH5 Variant.

Morishita Y, Hamada M, Uemura S, Kikuchi H, Hisakawa H, Fujikawa T, Tamura A, Okuno Y, Wakamatsu M, Muramatsu H, Takahashi Y, Hasegawa D, Kosaka Y

Pediatric blood & cancer Vol. 72 ( 2 ) page： e31465 2025.2

Identification of a Novel Stomatal Opening Chemical, PP242, That Inhibits Early Abscisic Acid Signal Transduction in Guard Cells.

Oh A, Kimura R, Inoue S, Sato T, Hayashi Y, Sato A, Takahashi Y, Kinoshita T

Plant & cell physiology 2025.1

EMT-Induced Morphological Variations on Living Cell Membrane Surface.

Ida H, Taira N, Nashimoto Y, Kumatani A, Takahashi Y, Shiku H

Analytical chemistry Vol. 97 ( 1 ) page： 312 - 318 2025.1

Lattice-guided growth of dense arrays of aligned transition metal dichalcogenide nanoribbons with high catalytic reactivity. Open Access

Ma Z, Solís-Fernández P, Hirata K, Lin YC, Shinokita K, Maruyama M, Honda K, Kato T, Uchida A, Ogura H, Otsuka T, Hara M, Matsuda K, Suenaga K, Okada S, Kato T, Takahashi Y, Ago H

Science advances Vol. 11 ( 2 ) page： eadr8046 2025.1

Association between adeno-associated virus 2 and severe acute hepatitis of unknown etiology in Japanese children Reviewed

Ken-ichi Iwata, Yuka Torii, Aiko Sakai, Yuto Fukuda, Kazunori Haruta, Makoto Yamaguchi, Takako Suzuki, Yuri Etani, Yoshiyuki Takahashi, Shuichiro Umetsu, Ayano Inui, Ryo Sumazaki, Jun-ichi Kawada

Journal of Infection and Chemotherapy Vol. 31 ( 1 ) page： 102462 2025.1

Corrosion Inspection for Hard Disk Media with Carbon-Based Overcoats by In-Liquid Open-Loop Electric Potential Microscopy.

Hirata K, Omi JI, Taniguchi D, Miyazawa K, Komatsu F, Takahashi Y, Fukuma T

ACS applied materials & interfaces Vol. 16 ( 50 ) page： 70020 - 70027 2024.12

Sleep state-dependent development of resting-state functional connectivity during the preterm period. Open Access

Shiraki A, Kidokoro H, Watanabe H, Taga G, Ushida T, Narita H, Mitsumatsu T, Kumai S, Suzui R, Sawamura F, Ito Y, Yamamoto H, Nakata T, Sato Y, Hayakawa M, Takahashi Y, Natsume J

Sleep Vol. 47 ( 12 ) 2024.12

Prospective Registration Study for Establishing Minimal Clinically Important Differences in Patients Undergoing Surgery for Spinal Metastases.

Hirota R, Oshigiri T, Iesato N, Emori M, Teramoto A, Shiratani Y, Suzuki A, Terai H, Shimizu T, Kakutani K, Kanda Y, Tominaga H, Kawamura I, Ishihara M, Paku M, Takahashi Y, Funayama T, Miura K, Shirasawa E, Inoue H, Kimura A, Iimura T, Moridaira H, Nakajima H, Watanabe S, Akeda K, Takegami N, Nakanishi K, Sawada H, Matsumoto K, Funaba M, Suzuki H, Funao H, Hirai T, Otsuki B, Kobayakawa K, Uotani K, Manabe H, Tanishima S, Hashimoto K, Iwai C, Yamabe D, Hiyama A, Seki S, Goto Y, Miyazaki M, Watanabe K, Nakamae T, Kaito T, Nakashima H, Nagoshi N, Kato S, Imagama S, Watanabe K, Inoue G, Furuya T

Spine Vol. 49 ( 22 ) page： 1539 - 1547 2024.11

Ruxolitinib for pediatric patients with treatment-naïve and steroid-refractory acute graft-versus-host disease: the REACH4 study.

Locatelli F, Kang HJ, Bruno B, Gandemer V, Rialland F, Faraci M, Takahashi Y, Koh K, Bittencourt H, Cleary G, Rosko C, Li X, St Pierre A, Prahallad A, Diaz-de-Heredia C

Blood Vol. 144 ( 20 ) page： 2095 - 2106 2024.11

Effects of Palliative Surgical Treatment for Spinal Metastases on the Patient's Quality of Life With a Focus on the Segment of the Metastasis: A Prospective Multicenter Study. Open Access

Segi N, Nakashima H, Ito S, Ouchida J, Shiratani Y, Shimizu T, Suzuki A, Terai H, Kakutani K, Kanda Y, Tominaga H, Kawamura I, Ishihara M, Paku M, Takahashi Y, Funaba M, Funayama T, Nakajima H, Akeda K, Hirai T, Inoue H, Nakanishi K, Funao H, Oshigiri T, Otsuki B, Kobayakawa K, Tanishima S, Hashimoto K, Iimura T, Sawada H, Uotani K, Manabe H, Iwai C, Yamabe D, Hiyama A, Seki S, Goto Y, Miyazaki M, Watanabe K, Nakamae T, Kaito T, Nagoshi N, Kato S, Watanabe K, Imagama S, Inoue G, Furuya T

Global spine journal page： 21925682241297948 2024.11

Frequent loss of HLA-B*40:02 from leucocytes in male patients with hepatitis-associated aplastic anaemia.

Katagiri T, Takahashi R, Zaimoku Y, Hosokawa K, Ogawa S, Takahashi Y, Miyamura T, Onishi Y, Koike T, Nishida T, Uchida N, Doki N, Tanaka M, Eto T, Itagaki M, Sawa M, Fukuda T, Onizuka M, Atsuta Y, Nakao S

British journal of haematology Vol. 205 ( 5 ) page： 2084 - 2088 2024.11

Association between combined use of epidural analgesia and oxytocin administration during labor and offspring outcomes: a narrative review and proposal. Open Access

Tachi A, Takahashi Y, Kotani T

Nagoya journal of medical science Vol. 86 ( 4 ) page： 549 - 563 2024.11

A Retrospective Study of Pediatric Patients With Low- or Intermediate-Risk Acute Myeloid Leukemia Who Underwent Allogeneic Hematopoietic Cell Transplantation for the AML-05 Study Conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group.

Hashii Y, Kawaguchi K, Kurakami H, Umeda K, Hasegawa D, Taki T, Hyakuna N, Ishida H, Takahashi Y, Nagasawa M, Yabe H, Yano M, Nakazawa Y, Fujisaki H, Matsumoto K, Yanagimachi M, Yoshida N, Kakuda H, Satou A, Tabuchi K, Tomizawa D, Taga T, Adachi S, Koh K, Kato K

Transplantation and cellular therapy Vol. 30 ( 11 ) page： 1102.e1 - 1102.e12 2024.11

The efficacy of wrapping with polyglycolic acid mesh and fibrin glue in preventing clinically relevant pancreatic fistula after minimally invasive distal pancreatectomy (WRAP Study): study protocol for a multicenter randomized controlled trial in Japan. Open Access

Baba H, Oba A, Tanaka K, Miura T, Ban D, Edanami M, Ishikawa Y, Ohgi K, Tanaka H, Shintakuya R, Ikenaga N, Ijichi T, Kiya Y, Muranushi R, Yamaki S, Miyazaki N, Takeuchi S, Aoki S, Mizui T, Tanaka M, Ueda H, Dei H, Takami H, Okada K, Nakata K, Mataki Y, Osakabe H, Shibuya K, Hashimoto D, Inoue Y, Hirano S, Unno M, Esaki M, Kitago M, Akahoshi K, Sugiura T, Ebata T, Uemura K, Nakamura M, Otsuka T, Nagakawa Y, Fujii T, Satoi S, Takahashi Y

BMC surgery Vol. 24 ( 1 ) page： 314 2024.10

Statistically and functionally fine-mapped blood eQTLs and pQTLs from 1,405 humans reveal distinct regulation patterns and disease relevance. Open Access

Wang QS, Hasegawa T, Namkoong H, Saiki R, Edahiro R, Sonehara K, Tanaka H, Azekawa S, Chubachi S, Takahashi Y, Sakaue S, Namba S, Yamamoto K, Shiraishi Y, Chiba K, Tanaka H, Makishima H, Nannya Y, Zhang Z, Tsujikawa R, Koike R, Takano T, Ishii M, Kimura A, Inoue F, Kanai T, Fukunaga K, Ogawa S, Imoto S, Miyano S, Okada Y, Japan COVID-19 Task Force

Nature genetics Vol. 56 ( 10 ) page： 2054 - 2067 2024.10

Publisher Correction: Statistically and functionally fine-mapped blood eQTLs and pQTLs from 1,405 humans reveal distinct regulation patterns and disease relevance. Open Access

Nature genetics Vol. 56 ( 10 ) page： 2281 2024.10

Does an early hands-on breastfeeding intervention by midwives affect nipple pain incidence? An observational pilot study. Open Access

Takahashi Y, Brimdyr K, Cadwell K

Japan journal of nursing science : JJNS Vol. 21 ( 4 ) page： e12613 2024.10

CO2 response screen in grass Brachypodium reveals the key role of a MAP kinase in CO2-triggered stomatal closure. Open Access

Lopez BNK, Ceciliato PHO, Takahashi Y, Rangel FJ, Salem EA, Kernig K, Chow K, Zhang L, Sidhom MA, Seitz CG, Zheng T, Sibout R, Laudencia-Chingcuanco DL, Woods DP, McCammon JA, Vogel JP, Schroeder JI

Plant physiology Vol. 196 ( 1 ) page： 495 - 510 2024.9

A Japanese retrospective study of non-tuberculous mycobacterial infection in children, adolescents, and young adult patients with hematologic-oncologic diseases. Open Access

Tsumura Y, Muramatsu H, Tetsuka N, Imaizumi T, Sato K, Inoue K, Motomura Y, Cho Y, Yamashita D, Sajiki D, Maemura R, Yamamori A, Imaya M, Wakamatsu M, Narita K, Kataoka S, Hamada M, Taniguchi R, Nishikawa E, Narita A, Nishio N, Kojima S, Hoshino Y, Takahashi Y

Haematologica Vol. 109 ( 9 ) page： 2988 - 2997 2024.9

Superatomic Layer of Cubic Mo(4)S(4) Clusters Connected by Cl Cross-Linking. Open Access

Nakanishi Y, Kanda N, Aizaki M, Hirata K, Takahashi Y, Endo T, Lin YC, Senga R, Suenaga K, Aoyagi S, Maruyama M, Gao Y, Okada S, Miyata Y, Liu Z

Advanced materials (Deerfield Beach, Fla.) Vol. 36 ( 39 ) page： e2404249 2024.9

High threshold of total developmental quotient at 3 years for follow-up in extremely preterm infants. Open Access

Maeda T, Tanahashi Y, Asada H, Kidokoro H, Takahashi Y, Sato Y

Early human development Vol. 196 page： 106098 2024.9

Correction: Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the EBMT, ASTCT, CIBMTR, and APBMT. Open Access

Sureda A, Carpenter PA, Bacigalupo A, Bhatt VR, de la Fuente J, Ho A, Kean L, Lee JW, Sánchez-Ortega I, Savani BN, Schetelig J, Stadtmauer EA, Takahashi Y, Atsuta Y, Koreth J, Kröger N, Ljungman P, Okamoto S, Popat U, Soiffer R, Stefanski HE, Kharfan-Dabaja MA

Bone marrow transplantation Vol. 59 ( 9 ) page： 1335 2024.9

Developing competencies relating to information science and technology in Japanese undergraduate medical education. Open Access

Onoue T, Asada Y, Imafuku R, Kou S, Takami H, Takahashi Y, Nomura O, Saiki T

Medical teacher Vol. 46 ( sup1 ) page： S31 - S37 2024.9

Variations of organic functional chemistry in carbonaceous matter from the asteroid 162173 Ryugu. Open Access

De Gregorio B, Cody GD, Stroud RM, David Kilcoyne AL, Sandford S, Le Guillou C, Nittler LR, Barosch J, Yabuta H, Martins Z, Kebukawa Y, Okumura T, Hashiguchi M, Yamashita S, Takeichi Y, Takahashi Y, Wakabayashi D, Engrand C, Bejach L, Bonal L, Quirico E, Remusat L, Duprat J, Verdier-Paoletti M, Mostefaoui S, Komatsu M, Mathurin J, Dazzi A, Deniset-Besseau A, Dartois E, Tamenori Y, Suga H, Montagnac G, Kamide K, Shigenaka M, Matsumoto M, Enokido Y, Yoshikawa M, Saiki T, Tanaka S, Terui F, Nakazawa S, Usui T, Abe M, Okada T, Yada T, Nishimura M, Nakato A, Miyazaki A, Yogata K, Yurimoto H, Nakamura T, Noguchi T, Okazaki R, Naraoka H, Sakamoto K, Tachibana S, Watanabe SI, Tsuda Y

Nature communications Vol. 15 ( 1 ) page： 7488 2024.8

Impact of surgical treatment on patient reported outcome in patients with spinal metastases from prostate cancer.

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2024.8

Ruxolitinib in treatment-naive or corticosteroid-refractory paediatric patients with chronic graft-versus-host disease (REACH5): interim analysis of a single-arm, multicentre, phase 2 study.

Locatelli F, Antmen B, Kang HJ, Koh K, Takahashi Y, Kupesiz A, Dias Matos MGA, Chopra Y, Bhat S, Im HJ, Güngör T, Lu MY, Stefanelli T, Rosko C, St Pierre A, Burock K, Smith Y, Sinclair K, Diaz-de-Heredia C

The Lancet. Haematology Vol. 11 ( 8 ) page： e580 - e592 2024.8

National registry of thoracoamniotic shunting using a double-basket catheter: A post-marketing surveillance registry of 295 patients with fetal hydrothorax.

Takahashi Y, Ishii K, Ishikawa H, Imai K, Baba K, Sago H

Prenatal diagnosis Vol. 44 ( 8 ) page： 971 - 978 2024.7

Does Preoperative Manual Reduction (Omoto Technique) Affect Surgical Outcomes for Calcaneal Fractures? A Multicenter (TRON Group) Retrospective Study.

Takahashi H, Takegami Y, Tokutake K, Takahashi Y, Kato M, Mabuchi M, Imagama S

The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons Vol. 63 ( 4 ) page： 450 - 455 2024.7

Clinical features of immature leukemias in children.

Sajiki D, Yoshida N, Muramatsu H, Sakaguchi K, Maeda N, Yokoyama N, Miyajima Y, Tanaka M, Takahashi Y, Hama A

International journal of hematology Vol. 120 ( 1 ) page： 117 - 127 2024.7

Analysis of Calcaneal Avulsion Fractures Treated Surgically and Nonsurgically: A Retrospective Multicenter Study. Open Access

Takahashi Y, Takegami Y, Tokutake K, Asami Y, Takahashi H, Kato M, Kanemura T, Imagama S

JB & JS open access Vol. 9 ( 3 ) 2024.7

Combination of Measurements of the Top Quark Mass from Data Collected by the ATLAS and CMS Experiments at sqrt[s]=7 and 8 TeV.

Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, Dragicevic M, Hussain PS, Jeitler M, Krammer N, Li A, Liko D, Mikulec I, Schieck J, Schöfbeck R, Schwarz D, Sonawane M, Templ S, Waltenberger W, Wulz CE, Darwish MR, Janssen T, Van Mechelen P, Bols ES, D'Hondt J, Dansana S, De Moor A, Delcourt M, El Faham H, Lowette S, Makarenko I, Müller D, Sahasransu AR, Tavernier S, Tytgat M, Van Putte S, Vannerom D, Clerbaux B, De Lentdecker G, Favart L, Hohov D, Jaramillo J, Khalilzadeh A, Lee K, Mahdavikhorrami M, Malara A, Paredes S, Pétré L, Postiau N, Thomas L, Vanden Bemden M, Vander Velde C, Vanlaer P, De Coen M, Dobur D, Hong Y, Knolle J, Lambrecht L, Mestdach G, Rendón C, Samalan A, Skovpen K, Van Den Bossche N, van der Linden J, Wezenbeek L, Benecke A, Bruno G, Caputo C, Delaere C, Donertas IS, Giammanco A, Jaffel K, Jain S, Lemaitre V, Lidrych J, Mastrapasqua P, Mondal K, Tran TT, Wertz S, Alves GA, Coelho E, Hensel C, Menezes De Oliveira T, Moraes A, Rebello Teles P, Soeiro M, Aldá Júnior WL, Alves Gallo Pereira M, Barroso Ferreira Filho M, Brandao Malbouisson H, Carvalho W, Chinellato J, Da Costa EM, Da Silveira GG, De Jesus Damiao D, Fonseca De Souza S, Gomes De Souza R, Martins J, Mora Herrera C, Mota Amarilo K, Mundim L, Nogima H, Santoro A, Sznajder A, Thiel M, Vilela Pereira A, Bernardes CA, Calligaris L, Tomei TRFP, Gregores EM, Mercadante PG, Novaes SF, Orzari B, Padula SS, Aleksandrov A, Antchev G, Hadjiiska R, Iaydjiev P, Misheva M, Shopova M, Sultanov G, Dimitrov A, Litov L, Pavlov B, Petkov P, Petrov A, Shumka E, Keshri S, Thakur S, Cheng T, Guo Q, Javaid T, Yuan L, Hu Z, Liu J, Yi K, Chen GM, Chen HS, Chen M, Iemmi F, Jiang CH, Kapoor A, Liao H, Liu ZA, Sharma R, Song JN, Tao J, Wang C, Wang J, Wang Z, Zhang H, Agapitos A, Ban Y, Levin A, Li C, Li Q, Mao Y, Qian SJ, Sun X, Wang D, Yang H, Zhang L, Zhou C, You Z, Lu N, Bauer G, Gao X, Leggat D, Okawa H, Zhang Y, Lin Z, Lu C, Xiao M, Avila C, Barbosa Trujillo DA, Cabrera A, Florez C, Fraga J, Reyes Vega JA, Mejia Guisao J, Ramirez F, Rodriguez M, Ruiz Alvarez JD, Giljanovic D, Godinovic N, Lelas D, Sculac A, Kovac M, Sculac T, Bargassa P, Brigljevic V, Chitroda BK, Ferencek D, Mishra S, Starodumov A, Susa T, Attikis A, Christoforou K, Konstantinou S, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Saka H, Stepennov A, Finger M, Finger M, Kveton A, Ayala E, Carrera Jarrin E, Abdalla H, Assran Y, Mahmoud MA, Mohammed Y, Dewanjee RK, Ehataht K, Kadastik M, Lange T, Nandan S, Nielsen C, Pata J, Raidal M, Tani L, Veelken C, Kirschenmann H, Osterberg K, Voutilainen M, Bharthuar S, Brücken E, Garcia F, Havukainen J, Kallonen KTS, Kinnunen R, Lampén T, Lassila-Perini K, Lehti S, Lindén T, Lotti M, Martikainen L, Myllymäki M, Rantanen MM, Siikonen H, Tuominen E, Tuominiemi J, Luukka P, Petrow H, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Faure JL, Ferri F, Ganjour S, Gras P, Hamel de Monchenault G, Lohezic V, Malcles J, Rander J, Rosowsky A, Sahin MÖ, Savoy-Navarro A, Simkina P, Titov M, Tornago M, Baldenegro Barrera C, Beaudette F, Buchot Perraguin A, Busson P, Cappati A, Charlot C, Damas F, Davignon O, De Wit A, Falmagne G, Fontana Santos Alves BA, Ghosh S, Gilbert A, Granier de Cassagnac R, Hakimi A, Harikrishnan B, Kalipoliti L, Liu G, Motta J, Nguyen M, Ochando C, Portales L, Salerno R, Sauvan JB, Sirois Y, Tarabini A, Vernazza E, Zabi A, Zghiche A, Agram JL, Andrea J, Apparu D, Bloch D, Brom JM, Chabert EC, Collard C, Falke S, Goerlach U, Grimault C, Haeberle R, Le Bihan AC, Meena M, Saha G, Sessini MA, Van Hove P, Beauceron S, Blancon B, Boudoul G, Chanon N, Choi J, Contardo D, Depasse P, Dozen C, El Mamouni H, Fay J, Gascon S, Gouzevitch M, Greenberg C, Grenier G, Ille B, Laktineh IB, Lethuillier M, Mirabito L, Perries S, Purohit A, Vander Donckt M, Verdier P, Xiao J, Lomidze D, Lomidze I, Tsamalaidze Z, Botta V, Feld L, Klein K, Lipinski M, Meuser D, Pauls A, Röwert N, Teroerde M, Diekmann S, Dodonova A, Eich N, Eliseev D, Engelke F, Erdmann M, Fackeldey P, Fischer B, Hebbeker T, Hoepfner K, Ivone F, Jung A, Lee MY, Mastrolorenzo L, Mausolf F, Merschmeyer M, Meyer A, Mukherjee S, Noll D, Novak A, Nowotny F, Pozdnyakov A, Rath Y, Redjeb W, Rehm F, Reithler H, Sarkar U, Sarkisovi V, Schmidt A, Sharma A, Spah JL, Stein A, Torres Da Silva De Araujo F, Vigilante L, Wiedenbeck S, Zaleski S, Dziwok C, Flügge G, Haj Ahmad W, Kress T, Nowack A, Pooth O, Stahl A, Ziemons T, Zotz A, Aarup Petersen H, Aldaya Martin M, Alimena J, Amoroso S, An Y, Baxter S, Bayatmakou M, Becerril Gonzalez H, Behnke O, Belvedere A, Bhattacharya S, Blekman F, Borras K, Brunner D, Campbell A, Cardini A, Cheng C, Colombina F, Consuegra Rodríguez S, Correia Silva G, De Silva M, Eckerlin G, Eckstein D, Estevez Banos LI, Filatov O, Gallo E, Geiser A, Giraldi A, Greau G, Guglielmi V, Guthoff M, Hinzmann A, Jafari A, Jeppe L, Jomhari NZ, Kaech B, Kasemann M, Kaveh H, Kleinwort C, Kogler R, Komm M, Krücker D, Lange W, Leyva Pernia D, Lipka K, Lohmann W, Mankel R, Melzer-Pellmann IA, Mendizabal Morentin M, Metwally J, Meyer AB, Milella G, Mussgiller A, Nair LP, Nürnberg A, Otarid Y, Park J, Pérez Adán D, Ranken E, Raspereza A, Ribeiro Lopes B, Rübenach J, Saggio A, Scham M, Schnake S, Schütze P, Schwanenberger C, Selivanova D, Shchedrolosiev M, Sosa Ricardo RE, Stafford D, Vazzoler F, Ventura Barroso A, Walsh R, Wang Q, Wen Y, Wichmann K, Wiens L, Wissing C, Yang Y, Zimermmane Castro Santos A, Albrecht A, Albrecht S, Antonello M, Bein S, Benato L, Bonanomi M, Connor P, Eich M, El Morabit K, Fischer Y, Fröhlich A, Garbers C, Garutti E, Grohsjean A, Hajheidari M, Haller J, Jabusch HR, Kasieczka G, Keicher P, Klanner R, Korcari W, Kramer T, Kutzner V, Labe F, Lange J, Lobanov A, Matthies C, Mehta A, Moureaux L, Mrowietz M, Nigamova A, Nissan Y, Paasch A, Pena Rodriguez KJ, Quadfasel T, Raciti B, Rieger M, Savoiu D, Schindler J, Schleper P, Schröder M, Schwandt J, Sommerhalder M, Stadie H, Steinbrück G, 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JK, Wittgen M, Wobisch M, Wolffs Z, Wollrath J, Wolter MW, Wolters H, Wongel AF, Woodward EL, Worm SD, Wosiek BK, Woźniak KW, Wozniewski S, Wraight K, Wu C, Wu J, Wu M, Wu M, Wu SL, Wu X, Wu Y, Wu Z, Wuerzinger J, Wyatt TR, Wynne BM, Xella S, Xia L, Xia M, Xiang J, Xie M, Xie X, Xin S, Xiong A, Xiong J, Xu D, Xu H, Xu L, Xu R, Xu T, Xu Y, Xu Z, Xu Z, Yabsley B, Yacoob S, Yamaguchi Y, Yamashita E, Yamauchi H, Yamazaki T, Yamazaki Y, Yan J, Yan S, Yan Z, Yang HJ, Yang HT, Yang S, Yang T, Yang X, Yang X, Yang Y, Yang Y, Yang Z, Yao WM, Yap YC, Ye H, Ye H, Ye J, Ye S, Ye X, Yeh Y, Yeletskikh I, Yeo BK, Yexley MR, Yin P, Yorita K, Younas S, Young CJS, Young C, Yu C, Yu Y, Yuan M, Yuan R, Yue L, Zaazoua M, Zabinski B, Zaid E, Zak ZK, Zakareishvili T, Zakharchuk N, Zambito S, Zamora Saa JA, Zang J, Zanzi D, Zaplatilek O, Zeitnitz C, Zeng H, Zeng JC, Zenger DT, Zenin O, Ženiš T, Zenz S, Zerradi S, Zerwas D, Zhai M, Zhang B, Zhang DF, Zhang J, Zhang J, Zhang K, Zhang L, Zhang P, Zhang R, Zhang S, Zhang S, Zhang T, Zhang X, Zhang X, Zhang Y, Zhang Y, Zhang Y, Zhang Z, Zhang Z, Zhao H, Zhao T, Zhao Y, Zhao Z, Zhemchugov A, Zheng J, Zheng K, Zheng X, Zheng Z, Zhong D, Zhou B, Zhou H, Zhou N, Zhou Y, Zhou Y, Zhu CG, Zhu J, Zhu Y, Zhu Y, Zhuang X, Zhukov K, Zhulanov V, Zimine NI, Zinsser J, Ziolkowski M, Živković L, Zoccoli A, Zoch K, Zorbas TG, Zormpa O, Zou W, Zwalinski L, CMS Collaboration†, ATLAS Collaboration‡

Physical review letters Vol. 132 ( 26 ) page： 261902 2024.6

Impact of perineal pain and delivery related factors on interference with activities of daily living until 1 month postpartum: A longitudinal prospective study. Open Access

Yamada A, Takahashi Y, Usami Y, Tamakoshi K

BMC pregnancy and childbirth Vol. 24 ( 1 ) page： 446 2024.6

A novel mechanism of idiopathic orthostatic hypotension and hypocatecholaminemia due to autoimmunity against aromatic l-Amino acid decarboxylase.

Uenishi E, Seino Y, Nakashima A, Kato K, Kato M, Nagasaki H, Ishikawa K, Izumoto T, Yamamoto M, Takahashi Y, Sugimura Y, Oiso Y, Tsunekawa S

Biochemical and biophysical research communications Vol. 714 page： 149940 2024.6

Landscape of driver mutations and their clinical effects on Down syndrome-related myeloid neoplasms.

Sato T, Yoshida K, Toki T, Kanezaki R, Terui K, Saiki R, Ojima M, Ochi Y, Mizuno S, Yoshihara M, Uechi T, Kenmochi N, Tanaka S, Matsubayashi J, Kisai K, Kudo K, Yuzawa K, Takahashi Y, Tanaka T, Yamamoto Y, Kobayashi A, Kamio T, Sasaki S, Shiraishi Y, Chiba K, Tanaka H, Muramatsu H, Hama A, Hasegawa D, Sato A, Koh K, Karakawa S, Kobayashi M, Hara J, Taneyama Y, Imai C, Hasegawa D, Fujita N, Yoshitomi M, Iwamoto S, Yamato G, Saida S, Kiyokawa N, Deguchi T, Ito M, Matsuo H, Adachi S, Hayashi Y, Taga T, Saito AM, Horibe K, Watanabe K, Tomizawa D, Miyano S, Takahashi S, Ogawa S, Ito E

Blood Vol. 143 ( 25 ) page： 2627 - 2643 2024.6

A retrospective analysis of gene fusions and treatment outcomes in pediatric acute megakaryoblastic leukemia without Down syndrome. International journal Open Access

Kyogo Suzuki, Asahito Hama, Yusuke Okuno, Yinyan Xu, Atsushi Narita, Nao Yoshida, Hideki Muramatsu, Nobuhiro Nishio, Koji Kato, Seiji Kojima, Keon Hee Yoo, Yoshiyuki Takahashi

Haematologica Vol. 109 ( 6 ) page： 1936 - 1940 2024.6

Tomoko Fujikawa, Suguru Uemura, Daiichiro Hasegawa, Naoya Morisada, Sayaka Nakamura, Aiko Kozaki, Atsuro Saito, Kenji Kishimoto, Toshiaki Ishida, Takeshi Mori, Kimikazu Yakushijin, Yoshio Katayama, Daiki Yamashita, Manabu Wakamatsu, Motoharu Hamada, Hideki Muramatsu, Yoshiyuki Takahashi, Yoshiyuki Kosaka

Pediatric Blood & Cancer Vol. 71 ( 6 ) page： e30736 2024.6

Integrated proteogenomic analysis for inherited bone marrow failure syndrome. International journal Open Access

Manabu Wakamatsu, Hideki Muramatsu, Hironori Sato, Masaki Ishikawa, Ryo Konno, Daisuke Nakajima, Motoharu Hamada, Yusuke Okuno, Yusuke Kawashima, Asahito Hama, Masafumi Ito, Hideto Iwafuchi, Yoshiyuki Takahashi, Osamu Ohara

Leukemia Vol. 38 ( 6 ) page： 1256 - 1265 2024.6

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

Recent advances in in-depth data-independent acquisition proteomic analysis have enabled comprehensive quantitative analysis of >10,000 proteins. Herein, an integrated proteogenomic analysis for inherited bone marrow failure syndrome (IBMFS) was performed to reveal their biological features and to develop a proteomic-based diagnostic assay in the discovery cohort; dyskeratosis congenita (n = 12), Fanconi anemia (n = 11), Diamond-Blackfan anemia (DBA, n = 9), Shwachman-Diamond syndrome (SDS, n = 6), ADH5/ALDH2 deficiency (n = 4), and other IBMFS (n = 18). Unsupervised proteomic clustering identified eight independent clusters (C1-C8), with the ribosomal pathway specifically downregulated in C1 and C2, enriched for DBA and SDS, respectively. Six patients with SDS had significantly decreased SBDS protein expression, with two of these not diagnosed by DNA sequencing alone. Four patients with ADH5/ALDH2 deficiency showed significantly reduced ADH5 protein expression. To perform a large-scale rapid IBMFS screening, targeted proteomic analysis was performed on 417 samples from patients with IBMFS-related hematological disorders (n = 390) and healthy controls (n = 27). SBDS and ADH5 protein expressions were significantly reduced in SDS and ADH5/ALDH2 deficiency, respectively. The clinical application of this first integrated proteogenomic analysis would be useful for the diagnosis and screening of IBMFS, where appropriate clinical screening tests are lacking.

DOI： 10.1038/s41375-024-02263-1

Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the EBMT, ASTCT, CIBMTR, and APBMT. Open Access

Bone marrow transplantation Vol. 59 ( 6 ) page： 832 - 837 2024.6

Determinants of postpartum depression among women in Kampong Chhnang Province, Cambodia. Open Access

Guechhorng I, Inthaphatha S, Nishino K, Takahashi Y, Hamajima N, Yamamoto E

Archives of psychiatric nursing Vol. 50 page： 60 - 66 2024.6

Novel air-liquid interface culture model to investigate stiffness-dependent behaviors of alveolar epithelial cells. Open Access

Takahashi Y, Ito S, Wang J, Kim J, Matsumoto T, Maeda E

Biochemical and biophysical research communications Vol. 708 page： 149791 2024.5

Scoring system for diagnosis and pretreatment risk assessment of neuroblastoma using urinary biomarker combinations. International journal Open Access

Hizuru Amano, Hiroo Uchida, Kazuharu Harada, Atsushi Narita, Shigehisa Fumino, Yuji Yamada, Shun Kumano, Mayumi Abe, Takashi Ishigaki, Minoru Sakairi, Chiyoe Shirota, Takahisa Tainaka, Wataru Sumida, Kazuki Yokota, Satoshi Makita, Shuhei Karakawa, Yuichi Mitani, Shojiro Matsumoto, Yutaka Tomioka, Hideki Muramatsu, Nobuhiro Nishio, Tsuyoshi Osawa, Masataka Taguri, Katsuyoshi Koh, Tatsuro Tajiri, Motohiro Kato, Kimikazu Matsumoto, Yoshiyuki Takahashi, Akinari Hinoki

Cancer science Vol. 115 ( 5 ) page： 1634 - 1645 2024.5

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

The urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to develop a scoring system for the diagnosis and pretreatment risk assessment of neuroblastoma, incorporating age and other urinary catecholamine metabolite combinations. Urine samples from 227 controls (227 samples) and 68 patients with neuroblastoma (228 samples) were evaluated. First, the catecholamine metabolites vanillactic acid (VLA) and 3-methoxytyramine sulfate (MTS) were identified as urinary marker candidates through comprehensive analysis using liquid chromatography-mass spectrometry. The concentrations of these marker candidates and conventional markers were then compared among controls, patients, and numerous risk groups to develop a scoring system. Participants were classified into four groups: control, low risk, intermediate risk, and high risk, and the proportional odds model was fitted using the L2-penalized maximum likelihood method, incorporating age on a monthly scale for adjustment. This scoring model using the novel urine catecholamine metabolite combinations, VLA and MTS, had greater area under the curve values than the model using HVA and VMA for diagnosis (0.978 vs. 0.964), pretreatment risk assessment (low and intermediate risk vs. high risk: 0.866 vs. 0.724; low risk vs. intermediate and high risk: 0.871 vs. 0.680), and prognostic factors (MYCN status: 0.741 vs. 0.369, histology: 0.932 vs. 0.747). The new system also had greater accuracy in detecting missing high-risk neuroblastomas, and in predicting the pretreatment risk at the time of screening. The new scoring system employing VLA and MTS has the potential to replace the conventional adjunctive diagnostic method using HVA and VMA.

DOI： 10.1111/cas.16116

Single-Cell Transcriptomic Analysis of Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis

Effect of levodopa on pathological gait in Dravet syndrome: A randomized crossover trial using three-dimensional gait analysis. Open Access

Suzuki T, Natsume J, Ito Y, Ito T, Noritake K, Kinoshita F, Fukasawa T, Tsuji T, Itomi K, Kurahashi H, Kubota K, Okanishi T, Saitoh S, Sugiura H, Watanabe H, Takahashi Y, Kidokoro H

Epilepsia Vol. 65 ( 5 ) page： 1304 - 1313 2024.5

Comparison of Whole Blood and Plasma for Monitoring Cytomegalovirus and Epstein-Barr Virus. Open Access

Fukuda Y, Torii Y, Iwata KI, Haruta K, Yamaguchi M, Suzuki T, Narita A, Muramatsu H, Ogura Y, Takahashi Y, Ito Y, Kawada JI

The new microbiologica Vol. 47 ( 1 ) page： 52 - 59 2024.5

Takako Suzuki, Yoshitaka Sato, Yusuke Okuno, Yuka Torii, Yuto Fukuda, Kazunori Haruta, Makoto Yamaguchi, Yoshiki Kawamura, Asahito Hama, Atsushi Narita, Hideki Muramatsu, Tetsushi Yoshikawa, Yoshiyuki Takahashi, Hiroshi Kimura, Yoshinori Ito, Jun-ichi Kawada

Journal of Clinical Immunology Vol. 44 ( 4 ) page： 103 2024.4

Nanopore sequencing in distinguishing between wild-type and vaccine strains of Varicella-Zoster virus. International journal

Yuto Fukuda, Takako Suzuki, Ken-Ichi Iwata, Kazunori Haruta, Makoto Yamaguchi, Yuka Torii, Atsushi Narita, Hideki Muramatsu, Yoshiyuki Takahashi, Jun-Ichi Kawada

Vaccine Vol. 42 ( 11 ) page： 2927 - 2932 2024.4

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

BACKGROUND: The introduction of varicella vaccines into routine pediatric immunization programs has led to a considerable reduction in varicella incidence. However, there have been reports of varicella, herpes zoster, and meningitis caused by the vaccine strain of varicella-zoster virus (VZV), raising concerns. Establishing the relationship between the wild-type and vaccine strains in VZV infections among previously vaccinated individuals is crucial. Differences in the single nucleotide polymorphisms (SNPs) among vaccine strains can be utilized to identify the strain. In this study, we employed nanopore sequencing to identify VZV strains and analyzed clinical samples. METHODS: We retrospectively examined vesicle and cerebrospinal fluid samples from patients with VZV infections. One sample each of the wild-type and vaccine strains, previously identified using allelic discrimination real-time PCR and direct sequencing, served as controls. Ten samples with undetermined VZV strains were included. After DNA extraction, a long PCR targeting the VZV ORF62 region was executed. Nanopore sequencing identified SNPs, allowing discrimination between the vaccine and wild-type strains. RESULTS: Nanopore sequencing confirmed SNPs at previously reported sites (105,705, 106,262, 107,136, and 107,252), aiding in distinguishing between wild-type and vaccine strains. Among the ten unknown samples, nine were characterized as wild strains and one as a vaccine strain. Even in samples with low VZV DNA levels, nanopore sequencing was effective in strain identification. CONCLUSION: This study validates that nanopore sequencing is a reliable method for differentiating between the wild-type and vaccine strains of VZV. Its ability to produce long-read sequences is remarkable, allowing simultaneous confirmation of known SNPs and the detection of new mutations. Nanopore sequencing can serve as a valuable tool for the swift and precise identification of wild-type and vaccine strains and has potential applications in future VZV surveillance.

DOI： 10.1016/j.vaccine.2024.03.046

Nationwide survey of patients with multisystem proteinopathy in Japan. Open Access

Yamashita S, Takahashi Y, Hashimoto J, Murakami A, Nakamura R, Katsuno M, Izumi R, Suzuki N, Warita H, Aoki M, Japan MSP Study Group

Annals of clinical and translational neurology Vol. 11 ( 4 ) page： 938 - 945 2024.4

Multi-color polymer carbon dots synthesized from waste polyolefins through phenylenediamine-assisted hydrothermal processing.

Takahashi Y, Chan K, Zinchenko A

Chemosphere Vol. 354 page： 141685 2024.4

Comparison of the Outcomes of Plating, Screw Fixation, and Pinning in Sanders Type II Fractures: A Multicenter (TRON) Retrospective Study.

Kato M, Takegami Y, Tokutake K, Asami Y, Takahashi Y, Takahashi H, Kumagai H, Imagama S

The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons Vol. 63 ( 2 ) page： 171 - 175 2024.3

Most axonal mitochondria in cortical pyramidal neurons lack mitochondrial DNA and consume ATP.

Hirabayashi Y, Lewis TL Jr, Du Y, Virga DM, Decker AM, Coceano G, Alvelid J, Paul MA, Hamilton S, Kneis P, Takahashi Y, Gaublomme JT, Testa I, Polleux F

bioRxiv : the preprint server for biology 2024.2

IκB kinase phosphorylates cytoplasmic TDP-43 and promotes its proteasome degradation. Open Access

Iguchi Y, Takahashi Y, Li J, Araki K, Amakusa Y, Kawakami Y, Kobayashi K, Yokoi S, Katsuno M

The Journal of cell biology Vol. 223 ( 2 ) 2024.2

Dysbiosis of gut microbiota in patients with protein-losing enteropathy after the Fontan procedure.

Go K, Horiba K, Yamamoto H, Morimoto Y, Fukasawa Y, Ohashi N, Yasuda K, Ishikawa Y, Kuraishi K, Suzuki K, Ito Y, Takahashi Y, Kato T

International journal of cardiology Vol. 396 page： 131554 2024.2

愛知県における副腎白質ジストロフィー新生児マススクリーニングの2年間の実績と課題

中田智彦, 伊藤祐史, 若松学, 村松秀城, 山本啓之, 城所博之, 久保田一生, 山田晋一郎, 勝野雅央, 伊藤哲哉, 下澤伸行, 高橋義行, 夏目淳

日本小児科学会雑誌 Vol. 128 ( 2 ) page： 283 - 283 2024.2

Factors associated with perineal pain on the first postnatal day after vaginal delivery: a cross-sectional study of primiparous women. Open Access

Yamada A, Takahashi Y, Hirose M, Usami Y, Maruya S, Tamakoshi K

Nagoya journal of medical science Vol. 86 ( 1 ) page： 52 - 63 2024.2

Comparison of plasma proteomic profiles of patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and infectious mononucleosis. International journal

Kazunori Haruta, Takako Suzuki, Makoto Yamaguchi, Yuto Fukuda, Yuka Torii, Yoshiyuki Takahashi, Yoshinori Ito, Jun-Ichi Kawada

Journal of medical virology Vol. 96 ( 2 ) page： e29450 2024.2

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

Primary Epstein-Barr virus (EBV) infection occasionally causes EBV-infectious mononucleosis (EBV-IM) and EBV-hemophagocytic lymphohistiocytosis (EBV-HLH). Although EBV-IM is mostly mild and self-limiting, EBV-HLH is a life-threatening disease characterized by excessive immune activation. However, the pathogenesis of EBV-HLH is yet to be fully elucidated. A diagnostic biomarker for EBV-HLH is desirable because early diagnosis and treatment are critical for the effective management of patients. In this study, the proteomic profiling of plasma was performed using liquid chromatography-mass spectrometry to identify proteins specific to EBV-IM and EBV-HLH. Furthermore, pathway analysis was performed for the proteins upregulated in patients with EBV-IM and EBV-HLH. Compared to healthy controls, 63 and 18 proteins were upregulated in patients with EBV-IM and EBV-HLH, respectively. Pathway and process enrichment analyses revealed that the complement system was the most enriched category of upregulated proteins in EBV-IM, whereas proteins related to immune effector processes were the most enriched in EBV-HLH. Among the 18 proteins upregulated in EBV-HLH, seven were exclusive to EBV-HLH. These specific proteins were associated with three pathways, and apolipoprotein E was commonly found in all the pathways. Proteomic analysis may provide new insights into the host response to EBV infection and the pathogenesis of EBV-related diseases.

DOI： 10.1002/jmv.29450

Successful treatment of DOCK8 deficiency by allogeneic hematopoietic cell transplantation from alternative donors

Nanoscrolls of Janus Monolayer Transition Metal Dichalcogenides.

Kaneda M, Zhang W, Liu Z, Gao Y, Maruyama M, Nakanishi Y, Nakajo H, Aoki S, Honda K, Ogawa T, Hashimoto K, Endo T, Aso K, Chen T, Oshima Y, Yamada-Takamura Y, Takahashi Y, Okada S, Kato T, Miyata Y

ACS nano Vol. 18 ( 4 ) page： 2772 - 2781 2024.1

Retinoid Therapy for Neuroblastoma: Historical Overview, Regulatory Challenges, and Prospects. Open Access

Makimoto A, Fujisaki H, Matsumoto K, Takahashi Y, Cho Y, Morikawa Y, Yuza Y, Tajiri T, Iehara T

Cancers Vol. 16 ( 3 ) 2024.1

Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC.

Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, Abramowicz H, Abreu H, Abulaiti Y, Acharya BS, Adam Bourdarios C, Adamczyk L, Adamek L, Addepalli SV, Addison MJ, Adelman J, Adiguzel A, Adye T, Affolder AA, Afik Y, Agaras MN, Agarwala J, Aggarwal A, Agheorghiesei C, Ahmad A, Ahmadov F, Ahmed WS, Ahuja S, Ai X, Aielli G, Aikot A, Ait Tamlihat M, Aitbenchikh B, Aizenberg I, Akbiyik M, Åkesson TPA, Akimov AV, Akiyama D, Akolkar NN, Al Khoury K, Alberghi GL, Albert J, Albicocco P, Albouy GL, Alderweireldt S, Aleksa M, Aleksandrov IN, Alexa C, Alexopoulos T, Alfonsi F, Algren M, Alhroob M, Ali B, Ali HMJ, Ali S, Alibocus SW, Aliev M, Alimonti G, Alkakhi W, Allaire C, Allbrooke BMM, Allen JF, Allendes Flores CA, Allport PP, Aloisio A, Alonso F, Alpigiani C, Alvarez Estevez M, Alvarez Fernandez A, Alves Cardoso M, Alviggi MG, Aly M, Amaral Coutinho Y, Ambler A, Amelung C, Amerl M, Ames CG, Amidei D, Amor Dos Santos SP, Amos KR, Ananiev V, Anastopoulos C, Andeen T, Anders JK, 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Young Adult Secondary Cancer After Proton Beam Therapy: A Case Study. Open Access

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Brain Abnormalities in Becker Muscular Dystrophy: Evaluation by Voxel-Based DTI and Morphometric Analysis. Open Access

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Reassigning CI chondrite parent bodies based on reflectance spectroscopy of samples from carbonaceous asteroid Ryugu and meteorites. Open Access

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T cell receptor-engineered T cells derived from target human leukocyte antigen-DPB1-specific T cell can be a potential tool for therapy against leukemia relapse following allogeneic hematopoietic cell transplantation. Open Access

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Regulation of lipid synthesis in myelin modulates neural activity and is required for motor learning. Open Access

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Vedolizumab for children with intestinal graft-versus-host disease: a case report and literature review

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Nanopipette Fabrication Guidelines for SICM Nanoscale Imaging.

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Generation and purification of ACTH-secreting hPSC-derived pituitary cells for effective transplantation. Open Access

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Development of TCR-T cell therapy targeting mismatched HLA-DPB1 for relapsed leukemia after allogeneic transplantation.

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Skin-to-skin contact after birth: Developing a research and practice guideline. Open Access

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Single-cell sequencing on CD8(+) TILs revealed the nature of exhausted T cells recognizing neoantigen and cancer/testis antigen in non-small cell lung cancer. Open Access

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Human leukocyte antigen 7/8-matched unrelated bone marrow transplantation using anti-thymocyte globulin in children

Motoharu Hamada, Hideki Muramatsu, Yuka Torii, Kyogo Suzuki, Atsushi Narita, Taro Yoshida, Masayuki Imaya, Ayako Yamamori, Manabu Wakamatsu, Shunsuke Miwata, Kotaro Narita, Shinsuke Kataoka, Nozomu Kawashima, Rieko Taniguchi, Eri Nishikawa, Nobuhiro Nishio, Yoshinori Ito, Seiji Kojima, Yoshiyuki Takahashi

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Two Cases of Juvenile Myelomonocytic Leukemia and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Open Access

Yamamoto, H; Natsume, J; Kaneko, K; Takahashi, T; Wakamatsu, M; Ogawa, C; Kumai, S; Suzui, R; Sawamura, F; Shiraki, A; Nakata, T; Kidokoro, H; Muramatsu, H; Takahashi, Y

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1T/1H-SnS(2) Sheets for Electrochemical CO(2) Reduction to Formate.

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Successful living-donor liver transplantation for sustained liver failure even after resolution of infiltrative massive hepatic invasion of stage 4S neuroblastoma: a case report. Open Access

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CLINICAL VALIDATION OF NOVEL URINARY MARKERS FOR NEUROBLASTOMA DIAGNOSIS

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Droplet Digital PCR Development for Adenovirus Load Monitoring in Children after Hematopoietic Stem Cell Transplantation Open Access

Kazunori Haruta, Suguru Takeuchi, Makoto Yamaguchi, Kazuhiro Horiba, Takako Suzuki, Yuka Torii, Atsushi Narita, Hideki Muramatsu, Yoshiyuki Takahashi, Yoshinori Ito, Jun-ichi Kawada

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Germline and somatic RUNX1 variants in a pediatric bone marrow failure cohort. International journal Open Access

Ayako Yamamori, Motoharu Hamada, Hideki Muramatsu, Manabu Wakamatsu, Asahito Hama, Atsushi Narita, Yusuke Tsumura, Taro Yoshida, Takehiko Doi, Kazuki Terada, Takeshi Higa, Nobuyuki Yamamoto, Hiroki Miura, Mitsutaka Shiota, Kenichiro Watanabe, Nao Yoshida, Ryo Maemura, Masayuki Imaya, Shunsuke Miwata, Kotaro Narita, Shinsuke Kataoka, Rieko Taniguchi, Kyogo Suzuki, Nozomu Kawashima, Nobuhiro Nishio, Hideto Iwafuchi, Masafumi Ito, Seiji Kojima, Yusuke Okuno, Yoshiyuki Takahashi

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Hama, A; Taga, T; Tomizawa, D; Muramatsu, H; Hasegawa, D; Adachi, S; Yoshida, N; Noguchi, M; Sato, M; Okada, K; Koh, K; Mitsui, T; Takahashi, Y; Miyamura, T; Hashii, Y; Kato, K; Atsuta, Y; Okamoto, Y

BRITISH JOURNAL OF HAEMATOLOGY Vol. 201 ( 4 ) page： 747 - 756 2023.5

Graft-versus-host disease-free, relapse-free, second transplant-free survival in allogeneic hematopoietic cell transplantation for genetic disorders. International journal

Koji Kawaguchi, Katsutsugu Umeda, Satoshi Miyamoto, Nao Yoshida, Hiromasa Yabe, Takashi Koike, Michiko Kajiwara, Hiroshi Kawaguchi, Yoshiyuki Takahashi, Masataka Ishimura, Hirotoshi Sakaguchi, Asahito Hama, Yuko Cho, Maho Sato, Keisuke Kato, Atsushi Sato, Koji Kato, Ken Tabuchi, Yoshiko Atsuta, Kohsuke Imai

Bone marrow transplantation Vol. 58 ( 5 ) page： 600 - 602 2023.5

High-dose ubiquinol supplementation in multiple-system atrophy: a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial. Open Access

Mitsui J, Matsukawa T, Uemura Y, Kawahara T, Chikada A, Porto KJL, Naruse H, Tanaka M, Ishiura H, Toda T, Kuzuyama H, Hirano M, Wada I, Ga T, Moritoyo T, Takahashi Y, Mizusawa H, Ishikawa K, Yokota T, Kuwabara S, Sawamoto N, Takahashi R, Abe K, Ishihara T, Onodera O, Matsuse D, Yamasaki R, Kira JI, Katsuno M, Hanajima R, Ogata K, Takashima H, Matsushima M, Yabe I, Sasaki H, Tsuji S

EClinicalMedicine Vol. 59 page： 101920 2023.5

Safety and efficacy of post-haematopoietic cell transplantation maintenance therapy with blinatumomab for relapsed/refractory CD19-positive B-cell acute lymphoblastic leukaemia: protocol for a phase I-II, multicentre, non-blinded, non-controlled trial (JPLSG SCT-ALL-BLIN21). Open Access

Sakaguchi H, Umeda K, Kato I, Sakaguchi K, Hiramatsu H, Ishida H, Yabe H, Goto H, Kawahara Y, Yamashita YI, Sanada M, Deguchi T, Takahashi Y, Saito A, Noma H, Horibe K, Taga T, Adachi S, Transplantation and Cellular Therapy Committee of Japanese Childhood Cancer Group

BMJ open Vol. 13 ( 4 ) page： e070051 2023.4

Novel xeno-free and serum-free culturing condition to improve piggyBac transposon-based CD19 chimeric antigen receptor T-cell production and characteristics

Sanyanusin, M; Tudsamran, S; Thaiwong, R; Tawinwung, S; Nishio, N; Takahashi, Y; Hirankarn, N; Suppipat, K

CYTOTHERAPY Vol. 25 ( 4 ) page： 397 - 406 2023.4

Efficacy and safety of bevacizumab, irinotecan, and temozolomide combination for relapsed or refractory pediatric central nervous system embryonal tumor: a single-institution study.

Shiba Y, Motomura K, Taniguchi R, Kurimoto M, Mizutani K, Ohka F, Aoki K, Ito E, Nishikawa T, Yamaguchi J, Kibe Y, Shimizu H, Maeda S, Nakashima T, Suzuki H, Muramatsu H, Takahashi Y, Saito R

Journal of neurosurgery. Pediatrics Vol. 31 ( 6 ) page： 1 - 9 2023.3

Macromolecular organic matter in samples of the asteroid (162173) Ryugu. Open Access

Yabuta H, Cody GD, Engrand C, Kebukawa Y, De Gregorio B, Bonal L, Remusat L, Stroud R, Quirico E, Nittler L, Hashiguchi M, Komatsu M, Okumura T, Mathurin J, Dartois E, Duprat J, Takahashi Y, Takeichi Y, Kilcoyne D, Yamashita S, Dazzi A, Deniset-Besseau A, Sandford S, Martins Z, Tamenori Y, Ohigashi T, Suga H, Wakabayashi D, Verdier-Paoletti M, Mostefaoui S, Montagnac G, Barosch J, Kamide K, Shigenaka M, Bejach L, Matsumoto M, Enokido Y, Noguchi T, Yurimoto H, Nakamura T, Okazaki R, Naraoka H, Sakamoto K, Connolly HC Jr, Lauretta DS, Abe M, Okada T, Yada T, Nishimura M, Yogata K, Nakato A, Yoshitake M, Iwamae A, Furuya S, Hatakeda K, Miyazaki A, Soejima H, Hitomi Y, Kumagai K, Usui T, Hayashi T, Yamamoto D, Fukai R, Sugita S, Kitazato K, Hirata N, Honda R, Morota T, Tatsumi E, Sakatani N, Namiki N, Matsumoto K, Noguchi R, Wada K, Senshu H, Ogawa K, Yokota Y, Ishihara Y, Shimaki Y, Yamada M, Honda C, Michikami T, Matsuoka M, Hirata N, Arakawa M, Okamoto C, Ishiguro M, Jaumann R, Bibring JP, Grott M, Schröder S, Otto K, Pilorget C, Schmitz N, Biele J, Ho TM, Moussi-Soffys A, Miura A, Noda H, Yamada T, Yoshihara K, Kawahara K, Ikeda H, Yamamoto Y, Shirai K, Kikuchi S, Ogawa N, Takeuchi H, Ono G, Mimasu Y, Yoshikawa K, Takei Y, Fujii A, Iijima YI, Nakazawa S, Hosoda S, Iwata T, Hayakawa M, Sawada H, Yano H, Tsukizaki R, Ozaki M, Terui F, Tanaka S, Fujimoto M, Yoshikawa M, Saiki T, Tachibana S, Watanabe SI, Tsuda Y

Science (New York, N.Y.) Vol. 379 ( 6634 ) page： eabn9057 2023.2

Formation and evolution of carbonaceous asteroid Ryugu: Direct evidence from returned samples. Open Access

Nakamura T, Matsumoto M, Amano K, Enokido Y, Zolensky ME, Mikouchi T, Genda H, Tanaka S, Zolotov MY, Kurosawa K, Wakita S, Hyodo R, Nagano H, Nakashima D, Takahashi Y, Fujioka Y, Kikuiri M, Kagawa E, Matsuoka M, Brearley AJ, Tsuchiyama A, Uesugi M, Matsuno J, Kimura Y, Sato M, Milliken RE, Tatsumi E, Sugita S, Hiroi T, Kitazato K, Brownlee D, Joswiak DJ, Takahashi M, Ninomiya K, Takahashi T, Osawa T, Terada K, Brenker FE, Tkalcec BJ, Vincze L, Brunetto R, Aléon-Toppani A, Chan QHS, Roskosz M, Viennet JC, Beck P, Alp EE, Michikami T, Nagaashi Y, Tsuji T, Ino Y, Martinez J, Han J, Dolocan A, Bodnar RJ, Tanaka M, Yoshida H, Sugiyama K, King AJ, Fukushi K, Suga H, Yamashita S, Kawai T, Inoue K, Nakato A, Noguchi T, Vilas F, Hendrix AR, Jaramillo-Correa C, Domingue DL, Dominguez G, Gainsforth Z, Engrand C, Duprat J, Russell SS, Bonato E, Ma C, Kawamoto T, Wada T, Watanabe S, Endo R, Enju S, Riu L, Rubino S, Tack P, Takeshita S, Takeichi Y, Takeuchi A, Takigawa A, Takir D, Tanigaki T, Taniguchi A, Tsukamoto K, Yagi T, Yamada S, Yamamoto K, Yamashita Y, Yasutake M, Uesugi K, Umegaki I, Chiu I, Ishizaki T, Okumura S, Palomba E, Pilorget C, Potin SM, Alasli A, Anada S, Araki Y, Sakatani N, Schultz C, Sekizawa O, Sitzman SD, Sugiura K, Sun M, Dartois E, De Pauw E, Dionnet Z, Djouadi Z, Falkenberg G, Fujita R, Fukuma T, Gearba IR, Hagiya K, Hu MY, Kato T, Kawamura T, Kimura M, Kubo MK, Langenhorst F, Lantz C, Lavina B, Lindner M, Zhao J, Vekemans B, Baklouti D, Bazi B, Borondics F, Nagasawa S, Nishiyama G, Nitta K, Mathurin J, Matsumoto T, Mitsukawa I, Miura H, Miyake A, Miyake Y, Yurimoto H, Okazaki R, Yabuta H, Naraoka H, Sakamoto K, Tachibana S, Connolly HC Jr, Lauretta DS, Yoshitake M, Yoshikawa M, Yoshikawa K, Yoshihara K, Yokota Y, Yogata K, Yano H, Yamamoto Y, Yamamoto D, Yamada M, Yamada T, Yada T, Wada K, Usui T, Tsukizaki R, Terui F, Takeuchi H, Takei Y, Iwamae A, Soejima H, Shirai K, Shimaki Y, Senshu H, Sawada H, Saiki T, Ozaki M, Ono G, Okada T, Ogawa N, Ogawa K, Noguchi R, Noda H, Nishimura M, Namiki N, Nakazawa S, Morota T, Miyazaki A, Miura A, Mimasu Y, Matsumoto K, Kumagai K, Kouyama T, Kikuchi S, Kawahara K, Kameda S, Iwata T, Ishihara Y, Ishiguro M, Ikeda H, Hosoda S, Honda R, Honda C, Hitomi Y, Hirata N, Hirata N, Hayashi T, Hayakawa M, Hatakeda K, Furuya S, Fukai R, Fujii A, Cho Y, Arakawa M, Abe M, Watanabe S, Tsuda Y

Science (New York, N.Y.) Vol. 379 ( 6634 ) page： eabn8671 2023.2

Fetal growth restriction followed by early catch-up growth impairs pancreatic islet morphology in male rats. International journal Open Access

Mahboba Jabary, Atsuto Onoda, Yuma Kitase, Kazuto Ueda, Haruka Mimatsu, Shoji Go, Ryosuke Miura, Masahiro Tsuji, Yoshiyuki Takahashi, Masahiro Hayakawa, Yoshiaki Sato

Scientific reports Vol. 13 ( 1 ) page： 2732 - 2732 2023.2

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

Fetal growth restriction (FGR), followed by postnatal early catch-up growth, is associated with an increased risk of metabolic dysfunction, including type 2 diabetes in humans. This study aims to determine the effects of FGR and early catch-up growth after birth on the pathogenesis of type 2 diabetes, with particular attention to glucose tolerance, pancreatic islet morphology, and fibrosis, and to elucidate its mechanism using proteomics analysis. The FGR rat model was made by inducing mild intrauterine hypoperfusion using ameroid constrictors (ACs). On day 17 of pregnancy, ACs were affixed to the uterine and ovarian arteries bilaterally, causing a 20.9% reduction in birth weight compared to sham pups. On postnatal day 4 (P4), the pups were assigned to either the good nutrition (GN) groups with 5 pups per dam to ensure postnatal catch-up growth or poor nutrition groups with 15 pups per dam to maintain lower body weight. After weaning, all pups were fed regular chow food ad libitum (P21). Rats in both FGR groups developed glucose intolerance; however, male rats in the FGR good nutrition (FGR-GN) group also developed hypertriglyceridemia and dysmorphic pancreatic islets with fibrosis. A comprehensive and functional analysis of proteins expressed in the pancreas showed that FGR, followed by early catch-up growth, severely aggravated cell adhesion-related protein expression in male offspring. Thus, FGR and early catch-up growth caused pancreatic islet morphological abnormalities and fibrosis associated with the disturbance of cell adhesion-related protein expressions. These changes likely induce glucose intolerance and dyslipidemia in male rats.

DOI： 10.1038/s41598-023-28584-2

新規新生児マススクリーニングで診断し,乳児期にHLAハプロ移植を施行したムコ多糖症I型

若松学, 村松秀城, 横井克幸, 中島葉子, 山下大紀, 佐治木大知, 前村遼, 津村悠介, 山森彩子, 今屋雅之, 成田幸太郎, 谷口理恵子, 片岡伸介, 成田敦, 西尾信博, 酒井好美, 伊藤哲哉, 高橋義行

日本小児科学会雑誌 Vol. 127 ( 2 ) page： 244 - 244 2023.2

EBウイルス関連血球貪食性リンパ組織球症のシングルセルシーケンスによる病態解析

鈴木高子, 佐藤好隆, 鳥居ゆか, 福田悠人, 春田一憲, 山口慎, 奥野友介, 濱麻人, 高橋義行, 木村宏, 伊藤嘉規, 川田潤一

日本小児科学会雑誌 Vol. 127 ( 2 ) page： 190 - 190 2023.2

Medical records as screening tools for child death review in Japan.

Numaguchi A, Ishii A, Natsume J, Saitoh S, Aoki Y, Yoshikawa T, Isobe I, Okumura A, Seno H, Takahashi Y

Pediatrics international : official journal of the Japan Pediatric Society Vol. 65 ( 1 ) page： e15692 2023.1

Late gastroenterological complications in children after allogeneic hematopoietic stem cell transplantation: A retrospective cohort study and a case series of children treated with Kampo medicines Open Access

Nozomu Kawashima, Shinsuke Kataoka, Motoharu Hamada, Eri Nishikawa, Rieko Taniguchi, Atsushi Narita, Hideki Muramatsu, Nobuhiro Nishio, Yoshiyuki Takahashi

Traditional and Kampo Medicine 2023

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

Aim: This study aimed to describe children developing late gastrointestinal (GI) complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), focusing on Kampo medicine. Methods: At the Nagoya University Hospital Department of Pediatrics, 179 consecutive patients underwent allo-HSCT over five years, of whom 167 achieved engraftment and survived at least 100 days post transplant and therefore were included in the study. Results: Thirteen patients (7.8%) developed late GI symptoms. Among these, three had upper GI symptoms, three had lower GI symptoms, while seven had upper/lower GI symptoms. Total parenteral nutrition was administered in 10 (77%) patients for a median of 81 days (range: 20–303). Four (31%) had histologically proven graft-versus-host-disease (GVHD), two (15%) had adverse drug reactions, and one (8%) had a viral infection. All three patients with lower GI symptoms responded to Kampo formulas' warming interior [TM1]. Two patients with upper GI symptoms had epigastric rigidity and responded to Aurantii Fructus Immaturus-based formulas. One patient developed severe cachexia, which was successfully reversed with Kampo medicines. There were no adverse effects due to Kampo medicines. Conclusions: Late GI complications may be a burden on children after allo-HSCT. Kampo medicines may provide a safe and promising therapy to resolve GI symptoms not otherwise specified.

DOI： 10.1002/tkm2.1392

Ruxolitinib in Pediatric Patients with Treatment-Naive or Steroid-Refractory Acute Graft-Versus-Host Disease: Primary Findings from the Phase I/II REACH4 Study

Scopus

[Chimeric antigen receptor (CAR) T cells targeting CD19 for acute lymphoblastic leukemia].

Takahashi Y, Nishio N

[Rinsho ketsueki] The Japanese journal of clinical hematology Vol. 64 ( 9 ) page： 1184 - 1191 2023

Locatelli, F; Kang, HJ; Bruno, B; Gandemer, V; Rialland, F; Faraci, M; Takahashi, Y; Koh, K; Bittencourt, H; Cleary, G; Rosko, C; Roussou, P; St Pierre, A; Prahallad, A; Díaz-de-Heredia, C

BLOOD Vol. 140 page： 1376 - 1378 2022.11

Impact of the Coronavirus Disease 2019 Pandemic on the Clinical Features of Pediatric Respiratory Syncytial Virus Infection in Japan Reviewed Open Access

Shoko Ozeki, Jun-ichi Kawada, Daiki Yamashita, Chika Yasufuku, Takuya Akano, Masahiro Kato, Konomi Suzuki, Chihiro Tano, Kazuki Matsumoto, Shu-hei Mizutani, Ayumi Mori, Nobuhiro Nishio, Hiroyuki Kidokoro, Yoshihiro Yasui, Yoshiyuki Takahashi, Yoshiaki Sato, Anna Shiraki, Kazuto Ueda, Shotaro Ando, Noriko Nagai, Tsutomu Aoshima, Michio Suzuki, Tetsuo Kubota, Motomasa Suzuki, Satoru Doi, Daichi Fukumi, Yuichiro Sugiyama, Masafumi Morishita, Naoko Nishimura, Mizuki Takagi, Hirokazu Kurahashi, Yohei Takeuchi, Kenji Kuraishi, Osamu Shinohara, Takashi Kawabe, Nobuhiro Watanabe, Shinji Hasegawa, Taichiro Muto, Shinji Kido, Shinya Hara, Shin Hoshino

Open Forum Infectious Diseases Vol. 9 ( 11 ) page： ofac562 2022.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

Abstract

Background

Mitigation measures implemented during the coronavirus disease 2019 (COVID-19) pandemic remarkably reduced the incidence of infectious diseases among children. However, a re-emergence of respiratory syncytial virus (RSV) infection was observed in 2021 in Japan. We compared the clinical characteristics of hospitalized patients with RSV infection before and during COVID-19.

Methods

We retrospectively enrolled children aged &lt;6 years who were hospitalized with RSV infection in 18 hospitals and compared their clinical characteristics before (January 2019 to April 2020, 1675 patients) and during COVID-19 (September 2020 to December 2021, 1297 patients).

Results

The mean age of patients with RSV infection was significantly higher during COVID-19 than before (17.4 vs 13.7 months, P &lt; .001). Compared with before COVID-19, a 2.6-fold increase in RSV cases in the 2–5 years age group was observed from sentinel surveillance during COVID-19, whereas a 1.2-fold increase was noted in the same age group among hospitalized patients. On average for all patients, consolidation shadows obtained on radiography were less frequently observed (26.1 vs 29.6%, P = .04), and reduced respiratory assistance (42.2% vs 48.7%, P &lt; .001) and hospitalization stay (5.7 vs 6.0 days, P &lt; .001) was required in patients with RSV infection during COVID-19.

Conclusions

Coronavirus disease 2019 and social activity restriction caused epidemiological changes in pediatric RSV infections, and a majority of patients with RSV infection aged ≥2 years did not develop severe symptoms requiring hospitalization. The RSV symptoms during the COVID-19 outbreak were equivalent to or milder than in the previous seasons.

DOI： 10.1093/ofid/ofac562

CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY FOLLOWED BY UR-BMT IN TYROSINE KINASE INHIBITOR RESISTANT PEDIATRIC PH1-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA

Other Link： https://academic.oup.com/ofid/article-pdf/9/11/ofac562/47043659/ofac562.pdf

Imaya, M; Narita, A; Nishio, N; Wakamatsu, M; Taniguchi, R; Kataoka, S; Muramatsu, H; Ichikawa, D; Maeda, N; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 69 2022.11

Impact of human leukocyte antigen mismatch on outcomes after unrelated bone marrow transplantation in paediatric patients: A retrospective analysis by the JSTCT HLA working group

Kato, I; Sakaguchi, H; Kato, S; Sato, M; Noguchi, M; Yoshida, N; Koh, K; Koike, T; Yanagimachi, M; Kato, K; Takahashi, Y; Fujita, N; Sato, A; Hashii, Y; Tabuchi, K; Atsuta, Y; Morishima, S; Kanda, J

BRITISH JOURNAL OF HAEMATOLOGY Vol. 199 ( 3 ) page： 392 - 400 2022.11

LI-FRAUMENI SYNDROME DIAGNOSED BY ONCOGENE PANEL TESTING FOR RHABDOMYOSARCOMA

Taniguchi, R; Narita, A; Muramatsu, H; Yamashita, D; Sajiki, D; Imaya, M; Wakamatsu, M; Narita, K; Nishio, N; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 69 2022.11

INFANT WITH NEUROBLASTOMA STAGE 4S REQUIRING LIVING DONOR LIVER TRANSPLANTATION

Yamamori, A; Muramatsu, H; Wakamatsu, M; Kataoka, S; Tsuyuki, Y; Nishio, N; Shimoyama, Y; Karube, K; Ogura, Y; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 69 2022.11

DANAZOL ADDED TO IMMUNOSUPPRESSIVE THERAPY IN CHILDREN WITH APLASTIC ANEMIA: A PROPENSITY SCORE-MATCHED COHORT STUDY

Narita, A; Kudo, K; Muramatsu, H; Yagasaki, H; Kobayashi, R; Yabe, H; Ohara, A; Ohga, S; Kojima, S; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 69 2022.11

HEMATOLOGICAL ABNORMALITIES IN JACOBSEN SYNDROME: PATIENTS NOT ONLY DEVELOP THROMBOCYTOPENIA, BUT ALSO ANEMIA AND NEUTROPENIA

Yamashita, D; Muramatsu, H; Narita, A; Fujita, N; Koh, K; Umeda, K; Morihana, E; Hama, A; Ito, M; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 69 2022.11

TREC/KREC Newborn Screening followed by Next-Generation Sequencing for Severe Combined Immunodeficiency in Japan

Wakamatsu, M; Kojima, D; Muramatsu, H; Okuno, Y; Kataoka, S; Nakamura, F; Sakai, Y; Tsuge, I; Ito, T; Ueda, K; Saito, A; Morihana, E; Ito, Y; Ohashi, N; Tanaka, M; Tanaka, T; Kojima, S; Nakajima, Y; Ito, T; Takahashi, Y

JOURNAL OF CLINICAL IMMUNOLOGY Vol. 42 ( 8 ) page： 1696 - 1707 2022.11

RETROSPECTIVE NATIONWIDE SURVEY OF NONTUBERCULOUS MYCOBACTERIAL INFECTIONS IN PEDIATRIC HEMATOLOGY/ONCOLOGY PATIENTS

Tsumura, Y; Muramatsu, H; Nishikawa, E; Tetsuka, N; Narita, A; Inoue, K; Cho, Y; Motomura, Y; Hoshino, Y; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 69 2022.11

Kataoka, S; Yamamori, A; Imaya, M; Wakamatsu, M; Narita, K; Taniguchi, R; Narita, A; Muramatsu, H; Nishio, N; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 69 2022.11

THREE CASES OF ABNORMAL TREC VALUES WITH COPY NUMBER ALTERATIONS IDENTIFIED IN SCID NEWBORN SCREENING PROGRAM

Wakamatsu, M; Muramatsu, H; Kojima, D; Okuno, Y; Kataoka, S; Nakamura, T; Sakai, Y; Nakajima, Y; Ito, T; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 69 2022.11

THE DISAPPEARANCE OF MINIMAL RESIDUAL DISEASE IN BONE MARROW DEMONSTRATES GRAFT VERSUS NEUROBLASTOMA EFFECT AFTER KIR-LIGAND MISMATCHED ALLOGENEIC CBT

Alahmadi, R; Nishio, N; Wakamatsu, M; Kataoka, S; Narita, K; Taniguchi, R; Narita, A; Muramatsu, H; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 69 2022.11

RISK FACTORS FOR BLOOD STREAM INFECTIONS AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION IN CHILDREN

Sajiki, D; Muramatsu, H; Wakamatsu, M; Narita, K; Kataoka, S; Taniguchi, R; Narita, A; Nishio, N; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 69 2022.11

5p deletion with congenital diaphragmatic hernia: a case report Open Access

Kotani, T; Ushida, T; Nakamura, N; Imai, K; Iitani, Y; Tano, S; Iwagaki, S; Takahashi, Y; Ito, M; Hayakawa, M; Kajiyama, H

JOURNAL OF MEDICAL CASE REPORTS Vol. 16 ( 1 ) page： 390 2022.10

Involvement of the Thalamus, Hippocampus, and Brainstem in Hypsarrhythmia of West Syndrome: Simultaneous Recordings of Electroencephalography and fMRI Study Open Access

Maki, Y; Natsume, J; Ito, Y; Okai, Y; Bagarinao, E; Yamamoto, H; Ogaya, S; Takeuchi, T; Fukasawa, T; Sawamura, F; Mitsumatsu, T; Maesawa, S; Saito, R; Takahashi, Y; Kidokoro, H

AMERICAN JOURNAL OF NEURORADIOLOGY Vol. 43 ( 10 ) page： 1502 - 1507 2022.10

深層学習を用いた新生児頭部エコー画像による脳室周囲白質軟化症の発症予測

川口将宏, 城所博之, 白木杏奈, 山本啓之, 中田智彦, 夏目淳, 高橋義行, 伊藤倫太郎, 野田晴香, 前田剛志, 上田一仁, 伊藤美春, 佐藤義朗, 早川昌弘

日本小児科学会雑誌 Vol. 126 ( 10 ) page： 1445 - 1445 2022.10

Quantitative assessment of viral load in the blood and urine of patients with congenital cytomegalovirus infection using droplet digital PCR Open Access

Yamaguchi, M; Kawada, J; Torii, Y; Haruta, K; Suzuki, T; Horiba, K; Takahashi, Y; Ito, Y

JOURNAL OF MEDICAL VIROLOGY Vol. 94 ( 9 ) page： 4559 - 4564 2022.9

Clinical parameter-based prediction of DNA methylation classification generates a prediction model of prognosis in patients with juvenile myelomonocytic leukemia Open Access

Imaizumi, T; Meyer, J; Wakamatsu, M; Kitazawa, H; Murakami, N; Okuno, Y; Yoshida, T; Sajiki, D; Hama, A; Kojima, S; Takahashi, Y; Loh, M; Stieglitz, E; Muramatsu, H

SCIENTIFIC REPORTS Vol. 12 ( 1 ) page： 14753 2022.8

Whole-exome analysis of 177 pediatric patients with undiagnosed diseases. International journal Open Access

Kotaro Narita, Hideki Muramatsu, Satoshi Narumi, Yuji Nakamura, Yusuke Okuno, Kyogo Suzuki, Motoharu Hamada, Naoya Yamaguchi, Atsushi Suzuki, Yosuke Nishio, Anna Shiraki, Ayako Yamamori, Yusuke Tsumura, Fumi Sawamura, Masahiro Kawaguchi, Manabu Wakamatsu, Shinsuke Kataoka, Kohji Kato, Hideyuki Asada, Tetsuo Kubota, Yukako Muramatsu, Hiroyuki Kidokoro, Jun Natsume, Seiji Mizuno, Tomohiko Nakata, Hidehito Inagaki, Naoko Ishihara, Takahiro Yonekawa, Akihisa Okumura, Tomoo Ogi, Seiji Kojima, Tadashi Kaname, Tomonobu Hasegawa, Shinji Saitoh, Yoshiyuki Takahashi

Scientific reports Vol. 12 ( 1 ) page： 14589 - 14589 2022.8

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

Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24-35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.

DOI： 10.1038/s41598-022-14161-6

Microsatellite instability-high is rare events in refractory pediatric solid tumors. International journal Open Access

Taro Yoshida, Hideki Muramatsu, Manabu Wakamatsu, Rieko Taniguchi, Daisuke Ichikawa, Masato Nakaguro, Atsushi Natsume, Yoshiyuki Takahashi

Pediatric hematology and oncology Vol. 39 ( 5 ) page： 468 - 474 2022.8

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

Microsatellite instability (MSI)-high status is associated with good responsiveness to immune checkpoint inhibitors. Although MSI-high status has been actively investigated in pediatric brain tumors, studies of other pediatric solid tumors are lacking. Among 334 consecutive pediatric patients with solid tumors, we retrospectively analyzed formalin-fixed paraffin-embedded tumor tissues of 36 of 74 patients (49%) who died of disease. We assessed the MSI status in these tissues using five multiplexed markers. The results revealed that none of the patients had an MSI-high status. These results indicate that MSI-high status is a rare event in pediatric patients with refractory/relapsed solid tumors.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1998266.

DOI： 10.1080/08880018.2021.1998266

Prognostic factors of children and adolescents with T-cell acute lymphoblastic leukemia after allogeneic transplantation. International journal

Hisashi Ishida, Motohiro Kato, Yuta Kawahara, Sae Ishimaru, Yuho Najima, Shinichi Kako, Maho Sato, Mitsuteru Hiwatari, Maiko Noguchi, Keisuke Kato, Katsuyoshi Koh, Keiko Okada, Fuminori Iwasaki, Ryoji Kobayashi, Shunji Igarashi, Shoji Saito, Yoshiyuki Takahashi, Atsushi Sato, Junji Tanaka, Yoshiko Hashii, Yoshiko Atsuta, Hirotoshi Sakaguchi, Toshihiko Imamura

Hematological oncology Vol. 40 ( 3 ) page： 457 - 468 2022.8

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

Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, and some high-risk patients with ALL require hematopoietic stem cell transplantation (HSCT). Mainly due to small patient numbers, studies focusing specifically on children and adolescents with T-cell ALL (T-ALL) are limited. Using a nationwide registry, we retrospectively analyzed data from patients under 20 years old who underwent their first HSCT for T-ALL between 2000 and 2018. As a result, total 484 patients were included, and their median follow-up period was 6.9 years after HSCT for survivors. While patients receiving HSCT at first complete remission (CR) showed relatively good 5-year leukemia free survival (5yLFS, 73.5%), once relapse occurred, their prognosis was much worse (44.4%) even if they attained second remission again (p < 0.001). Among patients receiving HSCT at CR1, grade II-IV acute graft versus host disease was associated with worse overall and LFS than grade 0-I (5yLFS 69.5% vs. 82.1%, p = 0.026) mainly due to high non-relapse mortality. Among those patients, patients receiving related bone marrow transplantation, unrelated bone marrow transplantation, or unrelated cord blood transplantation showed similar survival (5yLFS, 73.2%, 76.3%, and 77.0%, respectively). For patients undergoing cord blood transplantation at CR1, total-body irradiation-based myeloablative conditioning was associated with better 5yLFS than other conditioning regimens (85.4% vs. 62.2%, p = 0.044), as it reduced the risk of relapse. These results indicate that relapsed patients have much less chance of cure, and that identifying patients who require HSCT for cure and offering them HSCT with optimal settings during CR1 are crucial for children and adolescents with T-ALL.

DOI： 10.1002/hon.2980

Risk factors for unplanned removal of central venous catheters in hospitalized children with hematological and oncological disorders.

Moe Miyagishima, Motoharu Hamada, Yuji Hirayama, Hideki Muramatsu, Takahisa Tainaka, Chiyoe Shirota, Akinari Hinoki, Takahiro Imaizumi, Masahiro Nakatochi, Michi Kamei, Eri Nishikawa, Nozomu Kawashima, Atsushi Narita, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

International journal of hematology Vol. 116 ( 2 ) page： 288 - 294 2022.8

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

Central venous catheters (CVCs) are essential devices in the treatment of pediatric patients with hematological and oncological disorders; however, the most suitable type of CVC for these patients remains unclear. We retrospectively compared risk factors for unplanned removal of two commonly used CVCs, peripherally inserted central catheters (PICCs) and tunneled CVCs, to propose which is the better device. We followed 89 patients fitted with a tunneled CVC (total 21,395 catheter-days) and 84 fitted with a PICC (total 9177 catheter-days) between January 1, 2013 and December 31, 2015, until catheter removal. Patients with a PICC had a significantly higher 3-month cumulative incidence of catheter occlusion (5.2% vs. 0%, p = 4.08 × 10-3) and total unplanned removals (29.0% vs. 6.9%, p = 0.0316) than those with tunneled CVCs. However, the cumulative incidence of central line-associated bloodstream infection did not differ significantly by CVC type. Multivariable analysis identified younger age (< 2 years) [sub-distribution hazard ratio (SHR) 2.29; 95% confidence interval (CI) 1.27-4.14] and PICC (SHR 2.73; 95% CI 1.48-5.02) as independent risk factors for unplanned removal. Thus, our results suggest that tunneled CVCs are preferable in pediatric patients with hematological and oncological disorders requiring long-term, intensive treatment.

DOI： 10.1007/s12185-022-03346-4

愛知県における重症複合免疫不全症に対するTREC新生児マススクリーニング検査

若松学, 村松秀城, 小島大英, 奥野友介, 片岡伸介, 成田敦, 中島葉子, 柘植郁哉, 酒井好美, 伊藤哲哉, 高橋義行

臨床血液 Vol. 63 ( 8 ) page： 957 - 957 2022.8

A patient with very early onset FH-deficient renal cell carcinoma diagnosed at age seven. International journal

Rieko Taniguchi, Hideki Muramatsu, Yusuke Okuno, Taro Yoshida, Manabu Wakamatsu, Motoharu Hamada, Chiyoe Shirota, Wataru Sumida, Akinari Hinoki, Takahisa Tainaka, Yoshimitsu Gotoh, Toyonori Tsuzuki, Yukichi Tanaka, Seiji Kojima, Hiroo Uchida, Yoshiyuki Takahashi

Familial cancer Vol. 21 ( 3 ) page： 337 - 341 2022.7

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

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline variants in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). HLRCC-associated RCC usually occurs in the middle age, with the median age being 40-44 years. This report describes a seven-year-old (84-month-old) male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. There was no evidence of distant metastasis. The male patient underwent right nephrectomy and has been recovering well without metastasis or recurrence. Pathological examination revealed that tumor cells with relatively prominent nucleoli and surrounded by halos, were located in a limited area. Immunohistochemical staining was negative for FH. Whole-exome sequencing identified his germline variant in the FH gene and its loss of heterozygosity in the tumor. At nine years (114 months) of age, the male patient showed no recurrence of the tumor. This was the youngest-onset case of HLRCC-associated RCC to date. This report may affect the starting age for future RCC-surveillance programs for patients with HLRCC.

DOI： 10.1007/s10689-021-00268-8

Difficulties in diagnosing Malassezia furfur bloodstream infection and possibility of spontaneous resolution in a patient undergoing chemotherapy for neuroblastoma: A case report. International journal Open Access

Nobuyuki Tetsuka, Hideki Muramatsu, Mitsutaka Iguchi, Keisuke Oka, Hiroshi Morioka, Yoshiyuki Takahashi, Tetsuya Yagi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Vol. 28 ( 7 ) page： 987 - 990 2022.7

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

Malassezia furfur is a lipophilic, yeast-like fungus that forms part of the normal human skin microflora and is associated with a wide range of infections, such as pityriasis versicolor, folliculitis, and systemic infections in immunocompromised patients. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has enabled rapid identification of Malassezia species, it is still a challenge to diagnose systemic infections because Malassezia fungemia can often be missed by automated blood culture systems. We report a case in which M. furfur in blood was detected by the presence of yeast-like fungi in blood smears. Yeast-like organisms were observed in the blood smears of a 3-year-old boy, taken over 2 weeks without any symptoms. He had undergone several courses of chemotherapy for neuroblastoma via an indwelling central venous catheter (CVC) that was placed in his right anterior chest for 11 months. Although the blood cultures obtained from an automated blood culture system were negative, M. furfur growth was detected in the subcultured blood taken from the CVC. The CVC was removed, and the scheduled chemotherapy was postponed. No systemic M. furfur bloodstream infection occurred; the infection resolved spontaneously without any specific treatment; only prophylactic fluconazole was administered. M. furfur fungemia may not be diagnosable by an automated blood culture system. Further, M. furfur may not cause infections in humans even when administered intravenously. This report may lead to the discovery of factors related to human infectivity of this disease in the future.

DOI： 10.1016/j.jiac.2022.02.026

Prognostic Factors for Outcomes of Allogeneic HSCT for Children and Adolescents/Young Adults With CML in the TKI Era. International journal Open Access

Hiroyuki Shimada, Akihiko Tanizawa, Takeshi Kondo, Tokiko Nagamura-Inoue, Masahiro Yasui, Arinobu Tojo, Hideki Muramatsu, Tetsuya Eto, Noriko Doki, Masatsugu Tanaka, Maho Sato, Maiko Noguchi, Naoyuki Uchida, Yoshiyuki Takahashi, Naoki Sakata, Tatsuo Ichinohe, Yoshiko Hashii, Koji Kato, Yoshiko Atsuta, Kazuteru Ohashi

Transplantation and cellular therapy Vol. 28 ( 7 ) page： 376 - 389 2022.7

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

The breakthrough effects of tyrosine kinase inhibitors (TKIs) have lessened indications for allogeneic hematopoietic stem cell transplantation (HSCT) in chronic myeloid leukemia (CML). However, HSCT is still attractive for children and adolescents/young adults (AYAs) requiring lifelong TKI therapy. Nevertheless, little has been reported on the outcomes of large clinical studies of HSCT targeting these age groups. This study aimed to identify prognostic factors for the outcomes of HSCT, including reduced-intensity conditioning (RIC)-HSCT, for children and AYAs with CML in the TKI era. We performed a registry analysis for 200 patients with CML aged <30 years who underwent pretransplant TKI therapy from the observational nationwide database established by the Japanese Society for Transplantation and Cellular Therapy. The patients received bone marrow (BM), peripheral blood (PB), or cord blood (CB) from either related or unrelated donors. The indication for HSCT for individual patients was determined by the institution according to European LeukemiaNet recommendations and other guidelines. The 5-year overall survival (OS) rates for patients with chronic phase (CP) (n = 124), accelerated phase (AP) (n = 23), and blastic phase (BP) (n = 53) at diagnosis were 82.8%, 71.1%, and 73.3%, respectively, with no significant difference (P =.3293). The strongest predictor of engraftment was transplant source, with CB (hazard ratio [HR], 0.33) and PB (HR, 2.00) (compared with BM) being independent unfavorable and favorable predictors, respectively. Transplant source was also an independent predictor of chronic GVHD, with PB (HR, 1.81) and CB (HR, 0.39) (compared with BM) being unfavorable and favorable predictors, respectively. The strongest predictor of OS rate for patients with CP at diagnosis was disease phase at HSCT, with second or greater CP, AP, or BP (HR, 2.81) (compared with first CP [CP1]) being an unfavorable predictor. In addition, patients with CP at diagnosis who had major and complete molecular responses at HSCT had excellent outcomes, with 5-year OS rates of 100% and 94.4%, respectively. The 5-year OS rate was compared between RIC (n = 31) and myeloablative conditioning (MAC) (n = 58) in patients with CP1, both of which were 89.3%, with no significant difference (P = .9440). On univariate analysis for the RIC cohort with CP at diagnosis, the age at HSCT (HR, 1.27) (increase per year) and the time from diagnosis to HSCT (HR, 1.83) (increase per year) were significant predictors for OS. Our study demonstrates that RIC may be an appropriate alternative to MAC for children and AYAs with CP1. As for the transplant source, we recommend first selecting BM because of a higher engraftment rate compared to CB and a lower incidence of chronic GVHD compared to PB. Although HSCT in the status of a major molecular response is desirable, it is not advisable to continue TKI pointlessly long because age at HSCT and timing of HSCT are prognostic factors that determine survival. The decision to perform RIC-HSCT instead of continuing TKI should be carefully made, considering the possibility of transplant-related complications.

DOI： 10.1016/j.jtct.2022.04.011

Registry data analysis of hematopoietic stem cell transplantation on systemic chronic active Epstein-Barr virus infection patients in Japan

[Recommendations (Proposal) for promoting research for overcoming neurological diseases 2020].

Mochizuki H, Aoki M, Ikenaka K, Inoue H, Iwatsubo T, Ugawa Y, Okazawa H, Ono K, Onodera O, Kitagawa K, Saito Y, Shimohata T, Takahashi R, Toda T, Nakahara J, Matsumoto R, Mizusawa H, Mitsui J, Murayama S, Katsuno M, Future Vision Committee of Japanese Society of Neurology, Aoki Y, Ishiura H, Izumi Y, Koike H, Shimada H, Takahashi Y, Tokuda T, Nakajima H, Hatano T, Misawa S, Watanabe H

Rinsho shinkeigaku = Clinical neurology Vol. 62 ( 6 ) page： 443 - 457 2022.6

[Recommendations (Proposal) for promoting research for overcoming neurological diseases 2020].

Rinsho shinkeigaku = Clinical neurology Vol. 62 ( 6 ) page： 429 - 442 2022.6

Yamamoto, M; Sato, M; Onishi, Y; Sasahara, Y; Sano, H; Masuko, M; Nakamae, H; Matsuoka, KI; Ara, T; Washio, K; Onizuka, M; Watanabe, K; Takahashi, Y; Hirakawa, T; Nishio, M; Sakashita, C; Kobayashi, T; Sawada, A; Ichinohe, T; Fukuda, T; Hashii, Y; Atsuta, Y; Arai, A

AMERICAN JOURNAL OF HEMATOLOGY Vol. 97 ( 6 ) page： 780 - 790 2022.6

METABOLOMICS OF URINARY METABOLITES IN CHILDHOOD RHABDOMYOSARCOMA TO DISCOVER NOVEL BIOMARKERS

Nakano, S; Uchida, H; Amano, H; Narita, A; Abe, M; Ishigaki, T; Sakairi, M; Shirota, C; Sumida, W; Makita, S; Takimoto, A; Okamoto, M; Yasui, A; Takada, S; Nakagawa, Y; Terui, Y; Sunagawa, M; Takahashi, Y; Osawa, T; Hinoki, A

PEDIATRIC BLOOD & CANCER Vol. 69 2022.6

TREC測定による新生児マススクリーニングを通じて診断されたX連鎖重症複合免疫不全症の1例

山下大紀, 村松秀城, 佐治木大知, 津村悠介, 前村遼, 今屋雅之, 山森彩子, 若松学, 片岡伸介, 濱田太立, 谷口理恵子, 川島希, 西川英里, 成田敦, 奥野友介, 西尾信博, 小島大英, 中島葉子, 柘植郁哉, 中村富美子, 酒井好美, 伊藤哲哉, 高橋義行

日本小児科学会雑誌 Vol. 126 ( 6 ) page： 970 - 970 2022.6

Combination chemotherapy consisting of irinotecan, etoposide, and carboplatin for refractory or relapsed neuroblastoma. International journal Open Access

Masayuki Imaya, Hideki Muramatsu, Atsushi Narita, Ayako Yamamori, Manabu Wakamatsu, Taro Yoshida, Shunsuke Miwata, Kotaro Narita, Daisuke Ichikawa, Motoharu Hamada, Eri Nishikawa, Nozomu Kawashima, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

Cancer medicine Vol. 11 ( 9 ) page： 1956 - 1964 2022.5

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

BACKGROUND: Patients with primary refractory and relapsed neuroblastoma have a poor prognosis since safe and effective chemotherapies for these patients are currently limited. The development of new chemotherapy regimens for these patients is imperative to improve survival outcomes. METHODS: We retrospectively analyzed 40 patients with refractory (n = 36) or relapsed (n = 4) neuroblastoma who received irinotecan, etoposide, and carboplatin (IREC) as a second-line treatment. We evaluated their therapeutic response and the toxicity of IREC. We also assessed the impact of UGT1A1 gene polymorphisms, which are involved in irinotecan metabolism, on outcomes and toxicity. RESULTS: A total of 112 cycles of IREC were administered to 40 patients with a median of 2 cycles per patient (range, 1-9). Six (15%) patients (UGT1A1 wild-type [n = 2] and heterozygous [n = 4]) showed objective responses, including partial response (n = 1), tumor shrinkage (n = 4), and improved findings on their MIBG scan (n = 1). Grade 4 neutropenia, grade 4 leukopenia, and grades 3-4 gastrointestinal toxicity were observed in 110 (98%), 88 (79%), and 3 (3%) cycles, respectively. There was no IREC-related mortality. Patients with UGT1A1 polymorphisms showed a higher frequency of grade 4 leukopenia, but these patients did not have increased treatment-related mortality or non-hematologic toxicity. CONCLUSIONS: IREC showed an objective response rate of 15% including 1 case with partial response. IREC was well tolerated regardless of UGT1A1 genotype. This study suggests that IREC is a promising second-line chemotherapy for refractory or relapsed neuroblastoma.

DOI： 10.1002/cam4.4529

Predictive factors of acute respiratory events during initial induction chemotherapy in patients with advanced neuroblastoma Open Access

Matsui, M; Makimoto, A; Nishio, N; Takahashi, Y; Urashima, M; Yuza, Y

CANCER REPORTS Vol. 5 ( 5 ) page： e1499 2022.5

脊髄圧迫によるoncologic emergencyを呈した大腰筋内の後腹膜腫瘍

片岡伸介, 佐治木大知, 津村悠介, 前村遼, 今屋雅之, 山森彩子, 若松学, 谷口理恵子, 濱田太立, 西川英里, 川島希, 成田敦, 村松秀城, 西尾信博, 高橋義行, 内田広夫, 中川洋一, 田井中貴久, 安井昭洋, 中黒匡人, 下山芳江

日本小児血液・がん学会雑誌 Vol. 59 ( 1 ) page： 72 - 72 2022.5

Minor PNH clones do not distinguish inherited bone marrow failure syndromes from immune-mediated aplastic anemia. International journal Open Access

Atsushi Narita, Shunsuke Miwata, Masayuki Imaya, Yusuke Tsumura, Ayako Yamamori, Manabu Wakamatsu, Motoharu Hamada, Rieko Taniguchi, Yusuke Okuno, Hideki Muramatsu, Yoshiyuki Takahashi

Blood advances Vol. 6 ( 8 ) page： 2517 - 2519 2022.4

Death review of children receiving medical care at home. International journal Open Access

Jun Natsume, Atsushi Numaguchi, Atsuko Ohno, Mihoko Mizuno, Yoshiyuki Takahashi, Akihisa Okumura, Tetsushi Yoshikawa, Shinji Saitoh, Kiyokuni Miura, Masaharu Noda

Pediatric research Vol. 91 ( 5 ) page： 1286 - 1289 2022.4

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

BACKGROUND: Children receiving home medical care need special attention to prevent unexpected death. The aim of this study was to clarify the factors contributing to death in children receiving home medical care from the child death review database. METHODS: Children receiving home medical care were enrolled from the child death review database from 2014 to 2016 in Aichi prefecture, Japan, with a population of one million children. Types of medical care and factors contributing to death were examined. RESULTS: Of the 631 children who died, 40 children (6%) were receiving home medical care (21: tracheostomy; 19: ventilator; 26: suctioning of naso-oral secretions; 19: oxygen inhalation; 32: tube feeding; 6: urethral catheterization; and 1: peritoneal dialysis). The death rate was 50 times that in the general population of children. Ten children had contributory factors that seemed to be preventable. In four children, the families could not replace the tracheostomy tubes during an accident. In three, oxygen saturation or ventilator alarms were not set appropriately. In two, an oxygen cylinder became empty. One child fell down from a seat in a car. CONCLUSIONS: Improvement of devices and correct guidance to caregivers may reduce the death rate in children receiving home medical care. IMPACT: Children receiving home medical care, such as tracheostomy care, mechanical ventilation, or tube feeding, need special attention to prevent unexpected death. In this population-based child death review, 6% of children received home medical care, and it was estimated that 1 of 100 children receiving home medical care died per year. One-quarter of the deaths could be preventable by caregiver education or development of devices.

DOI： 10.1038/s41390-021-01606-3

Hematopoietic Cell Transplantation for Inborn Errors of Immunity Other than Severe Combined Immunodeficiency in Japan: Retrospective Analysis for 1985-2016. International journal Open Access

Satoshi Miyamoto, Katsutsugu Umeda, Mio Kurata, Masakatsu Yanagimachi, Akihiro Iguchi, Yoji Sasahara, Keiko Okada, Takashi Koike, Reo Tanoshima, Masataka Ishimura, Masafumi Yamada, Maho Sato, Yoshiyuki Takahashi, Michiko Kajiwara, Hiroshi Kawaguchi, Masami Inoue, Yoshiko Hashii, Hiromasa Yabe, Koji Kato, Yoshiko Atsuta, Kohsuke Imai, Tomohiro Morio

Journal of clinical immunology Vol. 42 ( 3 ) page： 529 - 545 2022.4

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

PURPOSE: Hematopoietic cell transplantation (HCT) is a curative therapy for most patients with inborn errors of immunity (IEI). We conducted a nationwide study on HCT for patients with IEI other than severe combined immunodeficiency (non-SCID) in Japan. METHODS: Data from the Japanese national database (Transplant Registry Unified Management Program, TRUMP) for 566 patients with non-SCID IEI, who underwent their first HCT between 1985 and 2016, were retrospectively analyzed. RESULTS: The 10-year overall survival (OS) and event-free survival (EFS) were 74% and 64%, respectively. The 10-year OS for HCT from unrelated bone marrow (URBM), accounting for 39% of HCTs, was comparable to that for HCT from matched sibling donor (MSD), 79% and 81%, respectively. HCT from unrelated cord blood (URCB), accounting for 28% of HCTs, was also common, with a 10-year OS of 69% but less robust engraftment. The intensity of conditioning was not associated with OS or neutrophil recovery; however, myeloablative conditioning was more frequently associated with infection-related death. Patients who received myeloablative irradiation showed poor OS. Multivariate analyses revealed that HCT in 1985-1995 (hazard ratio [HR], 2.0; P = 0.03), URCB (HR, 2.0; P = 0.01), and related donor other than MSD (ORD) (HR, 2.9; P < 0.001) were associated with poor OS, and URCB (HR, 3.6; P < 0.001) and ORD (HR, 2.7; P = 0.02) showed a higher incidence of retransplantation. CONCLUSIONS: We present the 1985-2016 status of HCT for non-SCID IEI in Japan with sufficient statistical power, highlighting the potential of URBM as an alternative donor and the feasibility of reduced intensity conditioning.

DOI： 10.1007/s10875-021-01199-w

Genetic Study of Fanconi Anemia in Infancy Revealed FANCI Mutations and Defective ALDH2 Variant: A Case Report

Urata, T; Imamura, T; Osone, S; Muramatsu, H; Takahashi, Y; Hosoi, H

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Vol. 44 ( 2 ) page： E438 - E441 2022.3

Short Report Nosocomial infection with rotavirus vaccine strain in paediatric patients with immunodeficiency

Miura, H; Taniguchi, K; Narita, K; Kawamura, Y; Kozawa, K; Muramatsu, H; Takahashi, Y; Ihira, M; Yoshikawa, T

JOURNAL OF HOSPITAL INFECTION Vol. 121 page： 9 - 13 2022.3

Prospective validation of the provisional entity of refractory cytopenia of childhood, proposed by the World Health Organization Open Access

Hama, A; Hasegawa, D; Manabe, A; Nozawa, K; Narita, A; Muramatsu, H; Kosaka, Y; Kobayashi, M; Koh, K; Takahashi, Y; Watanabe, K; Ohara, A; Ito, M; Kojima, S

BRITISH JOURNAL OF HAEMATOLOGY Vol. 196 ( 4 ) page： 1031 - 1039 2022.2

Targeting MEF2D-fusion Oncogenic Transcriptional Circuitries in B-cell Precursor Acute Lymphoblastic Leukemia

Tsuzuki, S; Yasuda, T; Kawazu, M; Ueno, T; Karnan, S; Ota, A; Sanada, M; Nagai, H; Tomita, A; Takahashi, Y; Miyazaki, Y; Matsumura, I; Kiyoi, H; Hosokawa, Y; Mano, H; Hayakawa, F

CANCER SCIENCE Vol. 113 page： 1236 - 1236 2022.2

Dyserythropoietic anaemia with an intronic GATA1 splicing mutation in patients suspected to have Diamond-Blackfan anaemia. International journal Open Access

Akie Kobayashi, Ryusei Ohtaka, Tsutomu Toki, Junichi Hara, Hideki Muramatsu, Rika Kanezaki, Yuka Takahashi, Tomohiko Sato, Takuya Kamio, Ko Kudo, Shinya Sasaki, Taro Yoshida, Taiju Utsugisawa, Hitoshi Kanno, Kenichi Yoshida, Yasuhito Nannya, Yoshiyuki Takahashi, Seiji Kojima, Satoru Miyano, Seishi Ogawa, Kiminori Terui, Etsuro Ito

EJHaem Vol. 3 ( 1 ) page： 163 - 167 2022.2

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

Diamond-Blackfan anaemia (DBA) shares clinical features with two recently reported sporadic cases of dyserythropoietic anaemia with a cryptic GATA1 splicing mutation (c.871-24 C>T). We hypothesized that some patients clinically diagnosed with DBA but whose causative genes were unknown may carry the intronic GATA1 mutation. Here, we examined 79 patients in our DBA cohort, who had no detectable causative genes. The intronic GATA1 mutation was identified in two male patients sharing the same pedigree that included multiple cases with anaemia. Cosegregation of this mutation and disease in multiple family members provide evidence to support the pathogenicity of the intronic GATA1 mutation.

DOI： 10.1002/jha2.374

New mimic of relapse or regional lymph node metastasis in a cancer survivor: a case of mRNA COVID-19 vaccine-induced lymphadenitis with high FDG uptake Open Access

胎児発育不全モデルラットの脳脊髄液中タンパク質の網羅的解析脳発達異常の病態解明に向けて

小野田淳人, 北瀬悠磨, 辻雅弘, 上田一仁, 高橋義行, 早川昌弘, 佐藤義朗

日本小児科学会雑誌 Vol. 126 ( 2 ) page： 414 - 414 2022.2

投与経路に着目したMultilineage-differentiating stress enduring cell(Muse細胞)を用いた新生児慢性肺疾患の新規治療法開発

三浦良介, 佐藤義朗, 小野田淳人, 藤本健志, 後藤良子, 高本幸奈, 神澤孝洋, 鈴木紗記子, 上田一仁, 徐悦, 橋本佑樹, 落合加奈代, 谷口顕信, 田中龍一, 伊藤美春, 齊藤明子, 村松友佳子, 清水忍, 高橋義行, 早川昌弘

日本小児科学会雑誌 Vol. 126 ( 2 ) page： 250 - 250 2022.2

TREC測定による新生児マススクリーニングにより診断され同種臍帯血移植を行ったX連鎖重症複合免疫不全症

山下大紀, 村松秀城, 今屋雅之, 山森彩子, 若松学, 片岡伸介, 濱田太立, 谷口理恵子, 川島希, 西川英里, 成田敦, 奥野友介, 西尾信博, 小島大英, 中島葉子, 柘植郁哉, 中村冨美子, 酒井好美, 伊藤哲哉, 高橋義行

日本小児科学会雑誌 Vol. 126 ( 2 ) page： 281 - 281 2022.2

TREC測定による新生児マススクリーニングにより診断され同種臍帯血移植を行ったX連鎖重症複合免疫不全症

日本小児科学会雑誌 Vol. 126 ( 2 ) page： 281 - 281 2022.2

Tsumura, Y; Asakura, K; Takahashi, I; Akaihata, M; Takahashi, Y; Ishida, Y

IMMUNOLOGICAL MEDICINE Vol. 45 ( 1 ) page： 45 - 47 2022.1

Dorsal myelopathy after nelarabine and intrathecal methotrexate therapy

Sawamura, F; Natsume, J; Nakata, T; Muramatsu, H; Takahashi, Y

PEDIATRICS INTERNATIONAL Vol. 64 ( 1 ) page： e15334 2022.1

Conception by assisted reproductive technology in infants with critical congenital heart disease in Japan.

Morimoto Y, Go K, Yamamoto H, Fukasawa Y, Nakai M, Morihana E, Yasuda K, Nishikawa H, Ohashi N, Takahashi Y, Kato T

Reproductive biomedicine online Vol. 44 ( 1 ) page： 163 - 170 2022.1

Clinical Impact of Melphalan Pharmacokinetics on Transplantation Outcomes in Children Undergoing Hematopoietic Stem Cell Transplantation. International journal Open Access

Ryo Maemura, Manabu Wakamatsu, Kana Matsumoto, Hirotoshi Sakaguchi, Nao Yoshida, Asahito Hama, Taro Yoshida, Shunsuke Miwata, Hironobu Kitazawa, Kotaro Narita, Shinsuke Kataoka, Daisuke Ichikawa, Motoharu Hamada, Rieko Taniguchi, Kyogo Suzuki, Nozomu Kawashima, Eri Nishikawa, Atsushi Narita, Yusuke Okuno, Nobuhiro Nishio, Koji Kato, Seiji Kojima, Kunihiko Morita, Hideki Muramatsu, Yoshiyuki Takahashi

Cell transplantation Vol. 31 page： 9636897221143364 - 9636897221143364 2022

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

Melphalan is widely used for hematopoietic stem cell transplantation (HSCT) conditioning. However, the relationship between its pharmacokinetic (PK) and transplantation outcomes in children has not been thoroughly investigated. We prospectively analyzed the relationship between melphalan area under the curve (AUC) and transplantation outcome and examined the development of a predictive model for melphalan clearance in children. This study included 43 children aged 0 to 19 years who underwent HSCT following a melphalan-based conditioning regimen from 2017 to 2021. In univariable analysis, high-melphalan AUC resulted in a significantly lower cumulative incidence of acute graft-versus-host disease and a higher cumulative incidence of thrombotic microangiopathy, although no significant difference was observed in survival. Regression analysis of a randomly selected derivation cohort (n = 21) revealed the following covariate PK model: predicted melphalan clearance (mL/min) = 6.47 × 24-h urinary creatinine excretion rate (CER, g/day) × 24-h creatinine clearance rate (CCR, mL/min) + 92.8. In the validation cohort (n = 22), the measured melphalan clearance values were significantly correlated with those calculated based on the prediction equation (R2 = 0.663). These results indicate that melphalan exposure may be optimized by adjusting the melphalan dose according to CER and CCR.

DOI： 10.1177/09636897221143364

Simple and robust methylation test for risk stratification of patients with juvenile myelomonocytic leukemia. International journal Open Access

Hironobu Kitazawa, Yusuke Okuno, Hideki Muramatsu, Kosuke Aoki, Norihiro Murakami, Manabu Wakamatsu, Kyogo Suzuki, Kotaro Narita, Shinsuke Kataoka, Daisuke Ichikawa, Motoharu Hamada, Rieko Taniguchi, Nozomu Kawashima, Eri Nishikawa, Atsushi Narita, Nobuhiro Nishio, Asahito Hama, Mignon L Loh, Elliot Stieglitz, Seiji Kojima, Yoshiyuki Takahashi

Blood advances Vol. 5 ( 24 ) page： 5507 - 5518 2021.12

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

Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm that develops during infancy and early childhood. The array-based international consensus definition of DNA methylation has recently classified patients with JMML into the following 3 groups: high (HM), intermediate (IM), and low methylation (LM). To develop a simple and robust methylation clinical test, 137 patients with JMML were analyzed using the Digital Restriction Enzyme Analysis of Methylation (DREAM), which is a next-generation sequencing-based methylation analysis. Unsupervised consensus clustering of the discovery cohort (n = 99) using DREAM data identified HM (HM_DREAM; n = 35) and LM subgroups (LM_DREAM; n = 64). Of the 98 cases that could be compared with the international consensus classification, 90 HM (n = 30) and LM (n = 60) cases had 100% concordance with DREAM clustering results. Of the remaining 8 cases comprising the IM group, 4 were classified as belonging to the HM_DREAM group and 4 to the LM_DREAM group. A machine-learning classifier was successfully constructed using a support vector machine (SVM), which divided the validation cohort (n = 38) into HM (HM_SVM, n = 18) and LM (LM_SVM; n = 20) groups. Patients with the HM_SVM profile had a significantly poorer 5-year overall survival rate than those with the LM_SVM profile. In conclusion, we developed a robust methylation test using DREAM for patients with JMML. This simple and straightforward test can be easily incorporated into diagnosis to generate a methylation classification for patients so they can receive risk-adapted treatment in the context of future clinical trials.

DOI： 10.1182/bloodadvances.2021005080

Altered effect of killer immunoglobulin-like receptor-ligand mismatch by graft versus host disease prophylaxis in cord blood transplantation

Yokoyama, H; Hirayama, M; Takahashi, Y; Uchida, N; Tanaka, M; Onizuka, M; Ozawa, Y; Onai, D; Katsuoka, Y; Wake, A; Sawa, M; Kobayashi, H; Maruyama, Y; Ozeki, K; Kimura, T; Kanda, J; Fukuda, T; Atsuta, Y; Terakura, S; Morishima, S

BONE MARROW TRANSPLANTATION Vol. 56 ( 12 ) page： 3059 - 3067 2021.12

Effectiveness of lacosamide in children and young adults previously treated with other sodium channel blockers

Suzuki, T; Natsume, J; Kumai, S; Maki, Y; Yamamoto, H; Numoto, S; Narahara, S; Kubota, T; Tsuji, T; Kato, T; Yamada, K; Maruyama, K; Okumura, A; Takahashi, Y; Kidokoro, H

EPILEPSY & BEHAVIOR Vol. 125 page： 108397 2021.12

Prognostic value of the revised International Prognostic Scoring System five-group cytogenetic abnormality classification for the outcome prediction of hematopoietic stem cell transplantation in pediatric myelodysplastic syndrome. International journal

Shohei Yamamoto, Motohiro Kato, Kenichiro Watanabe, Sae Ishimaru, Daisuke Hasegawa, Maiko Noguchi, Asahito Hama, Maho Sato, Takashi Koike, Fuminori Iwasaki, Hiroshi Yagasaki, Yoshiyuki Takahashi, Yoshiyuki Kosaka, Yoshiko Hashii, Akira Morimoto, Yoshiko Atsuta, Daiichiro Hasegawa, Nao Yoshida

Bone marrow transplantation Vol. 56 ( 12 ) page： 3016 - 3023 2021.12

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

Cytogenetic abnormalities are a major risk factor for relapse after hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS). We aimed to evaluate the value of the five-group cytogenetic classification according to the revised International Prognostic Scoring System (R-IPSS) for predicting the outcome after HSCT in pediatric patients with MDS. We retrospectively analyzed the Japanese registration data of 242 pediatric patients with MDS. According to the R-IPSS classification, 112 (45.5%) patients had good, 55 (22.7%) had intermediate, 64 (26.4%) had poor, and 11 (4.6%) had very poor cytogenetics. The 5-year overall survival (5yOS) was 72%, 69%, 59%, and 30% in the good, intermediate, poor, and very poor cytogenetic subgroups (p = 0.026), respectively. The very good, good, and intermediate subgroups were grouped into a "standard" subgroup and reclassified into three subgroups (standard, poor, and very poor). Patients with very poor risk had worse 5yOS (hazard ratio 2.17, 95% confidence interval (CI) 1.02-4.61; p = 0.04) and a much higher 5yCIR (hazard ratio 2.52, 95% CI 1.05-6.04; p = 0.04) than those of patients in the standard group in the multivariate analysis, indicating that very poor risk cytogenetic characteristics independently predicted worse outcome after HSCT in pediatric patients with MDS.

DOI： 10.1038/s41409-021-01446-z

A Phase I Study of CD19 Chimeric Antigen Receptor-T Cells Generated By the PiggyBac Transposon Vector for Acute Lymphoblastic Leukemia Open Access

[Recommendations (Proposal) for promoting research for overcoming neurological diseases 2020].

Rinsho shinkeigaku = Clinical neurology Vol. 61 ( 11 ) page： 709 - 721 2021.11

Nishio, N; Hanajiri, R; Ishikawa, Y; Murata, M; Taniguchi, R; Hamada, M; Nishikawa, E; Kawashima, N; Narita, A; Muramatsu, H; Takahashi, Y

BLOOD Vol. 138 page： 3831 - + 2021.11

Clinical Features of Immature Leukemias in Children

Sajiki, D; Yoshida, N; Muramatsu, H; Sakaguchi, K; Maeda, N; Yokoyama, N; Miyajima, Y; Tanaka, M; Takahashi, Y; Hama, A

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

A Case of FOXN1-SCID Identified by TREC/KREC Newborn Screening Program

Wakamatsu, M; Kojima, D; Muramatsu, H; Okuno, Y; Kataoka, S; Nakamura, T; Sakai, Y; Nakajima, Y; Ito, T; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

A Case of Severe Combined Immunodeficiency found in Newborn Screening for Primary Immunodeficiency in Aichi Prefecture

Yamashita, D; Wakamatsu, M; Muramatsu, H; Kojima, D; Kataoka, S; Okuno, Y; Nakamura, F; Sakai, Y; Ito, T; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

Cartilage-Hair Hypoplasia Diagnosed after Optional Screening of Neonates for Severe Combined Immunodeficiency

Tsumura, Y; Wakamatsu, M; Muramatsu, H; Okuno, Y; Nakajima, Y; Ito, T; Nakamura, T; Sakai, Y; Kojima, S; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

Clinical Characteristics and Outcomes of Acute Megakaryoblastic Leukemia with T(1;22)(P13;Q13) in Children

Hama, A; Nagai, K; Hasegawa, D; Hasegawa, D; Shimada, A; Takahashi, Y; Taga, T; Adachi, S; Tomizawa, D

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

A Case of Fanct without Abnormality in the Peripheral Blood Chromosome Breakage Test

Nishi, M; Eguchi, H; Muramatsu, H; Takahashi, Y; Matsuo, M

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

Hematopoietic Cell Transplantation for Severe Combined Immunodeficiency Patients: a Japanese Retrospective Study. International journal Open Access

Satoshi Miyamoto, Katsutsugu Umeda, Mio Kurata, Akira Nishimura, Masakatsu Yanagimachi, Masataka Ishimura, Maho Sato, Tomonari Shigemura, Motohiro Kato, Yoji Sasahara, Akihiro Iguchi, Takashi Koike, Yoshiyuki Takahashi, Michiko Kajiwara, Masami Inoue, Yoshiko Hashii, Hiromasa Yabe, Koji Kato, Yoshiko Atsuta, Kohsuke Imai, Tomohiro Morio

Journal of clinical immunology Vol. 41 ( 8 ) page： 1865 - 1877 2021.11

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

PURPOSE: Hematopoietic cell transplantation (HCT) is a curative therapy for patients with severe combined immunodeficiency (SCID). Here, we conducted a nationwide study to assess the outcome of SCID patients after HCT in Japan. METHODS: A cohort of 181 SCID patients undergoing their first allogeneic HCT in 1974-2016 was studied by using the Japanese national database (Transplant Registry Unified Management Program, TRUMP). RESULTS: The 10-year overall survival (OS) of the patients who received HCT in 2006-2016 was 67%. Umbilical cord blood (UCB) transplantation was performed in 81 patients (45%). The outcomes of HCT from HLA-matched UCB (n = 21) and matched sibling donors (n = 22) were comparable, including 10-year OS (91% vs. 91%), neutrophil recovery (cumulative incidence at 30 days, 89% vs. 100%), and platelet recovery (cumulative incidence at 60 days, 89% vs. 100%). Multivariate analysis of the patients who received HCT in 2006-2016 demonstrated that the following factors were associated with poor OS: bacterial or fungal infection at HCT (hazard ratio (HR): 3.8, P = 0.006), cytomegalovirus infection prior to HCT (HR: 9.4, P = 0.03), ≥ 4 months of age at HCT (HR: 25.5, P = 0.009), and mismatched UCB (HR: 19.8, P = 0.01). CONCLUSION: We showed the potential of HLA-matched UCB as a donor source with higher priority for SCID patients. We also demonstrated that early age at HCT without active infection is critical for a better prognosis, highlighting the importance of newborn screening for SCID.

DOI： 10.1007/s10875-021-01112-5

Urinary Biomarkers Predicting Treatment Outcomes in Neuroblastoma

Atsushi Narita, Akinari Hinoki, Kazuki Yokota, Motoharu Hamada, Shinsuke Kataoka, Nozomu Kawashima, Hideki Muramatsu, Nobuhiro Nishio, Hiroo Uchida, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

Using Chemotherapy to Treat Neuroblastoma Stage 4S with Hepatomegaly in a Patient Younger than 2 Months Old

Masayuki Imaya, Nobuhiro Nishio, Rieko Taniguchi, Shinsuke Kataoka, Motoharu Hamada, Eri Nishikawa, Nozomu Kawashima, Atsushi Narita, Hideki Muramatsu, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

Next-Generation Sequencing to Detect Pathogens in Pediatric Febrile Neutropenia: A Single-Center Retrospective Study of 112 Cases Open Access

Kazuhiro Horiba, Yuka Torii, Toshihiko Okumura, Suguru Takeuchi, Takako Suzuki, Jun-ichi Kawada, Hideki Muramatsu, Yoshiyuki Takahashi, Tomoo Ogi, Yoshinori Ito

Open Forum Infectious Diseases Vol. 8 ( 11 ) page： ofab223 2021.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

<title>Abstract</title>
<sec>
<title>Background</title>
Febrile neutropenia (FN) is a frequent complication in immunocompromised patients. However, causative microorganisms are detected in only 10% of patients. This study aimed to detect the microorganisms that cause FN using next-generation sequencing (NGS) to idenjpgy the genome derived from pathogenic microorganisms in the bloodstream. Here, we implemented a metagenomic approach to comprehensively analyze microorganisms present in clinical samples from patients with FN.

</sec>
<sec>
<title>Methods</title>
FN is defined as 1) a neutrophil count &lt; 500/µL, and 2) fever ≥ 37.5 °C. Plasma/serum samples of 112 pediatric patients with FN, 10 patients with neutropenia without fever (NE), were sequenced by NGS and analyzed by a metagenomic pipeline PATHDET.

</sec>
<sec>
<title>Results</title>
The putative pathogens were detected by NGS in 5 of 10 patients with FN with positive for blood culture results, 15 of 87 patients (17%) with negative for blood culture results, and 3 of 8 patients with NE. Several bacteria that were common in the oral, skin, and gut flora were commonly detected in blood samples, suggesting translocation of the human microbiota to the bloodstream in the setting of neutropenia. The cluster analysis of the microbiota in blood samples using NGS demonstrated that the representative bacteria of each cluster was mostly consistent with the pathogens in each patient.

</sec>
<sec>
<title>Conclusions</title>
NGS technique has a great potential for detecting causative pathogens in patients with FN. Cluster analysis, which extracts characteristic microorganisms from a complex microbial population, may be effective to detect pathogens in minute quantities of microbiota, such as those from the bloodstream.

</sec>

DOI： 10.1093/ofid/ofab223

RE-Treatment with CD19-Targeted CAR-T Cells for Relapse after CD19-CAR-T Cell Therapy

Nobuhiro Nishio, Motoharu Hamada, Eri Nishikawa, Nozomu Kawashima, Atsushi Narita, Hideki Muramatsu, Kai Wang, Huyong Zheng, Jung-Li Chang, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

Prolonged Hospitalization and Late Gastroenterological Complications in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Nozomu Kawashima, Shinsuke Kataoka, Motoharu Hamada, Eri Nishikawa, Rieko Taniguchi, Atsushi Narita, Hideki Muramatsu, Nobuhiro Nishio, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

Outcomes of KIR-Ligand Incompatible Allogeneic Cord Blood Transplantation for Relapsed Stage 4 Neuroblastoma: A Single Institutional Study

Shinsuke Kataoka, Nobuhiro Nishio, Manabu Wakamatsu, Rieko Taniguchi, Eri Nishikawa, Motoharu Hamada, Nozomu Kawashima, Atsushi Narita, Hideki Muramatsu, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

Strategy of Intensified Therapy for High Risk Pediatric Acute Lymphoblastic Leukemia Based on NGS-MRD-Based Risk Stratification

Motoharu Hamada, Masayuki Imaya, Yusuke Okuno, Nozomu Kawashima, Rieko Taniguchi, Atsushi Narita, Hideki Muramatsu, Nobuhiro Nishio, Shinji Hasegawa, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

Ten Patients with RUNX1 Mutation who were Suspected with FPD-MM in a Pediatric Cohort of Inherited Bone Marrow Failure Syndrome

Ayako Yamamori, Motoharu Hamada, Hideki Muramatsu, Rieko Taniguchi, Shinsuke Kataoka, Nozomu Kawashima, Atsushi Narita, Nobuhiro Nishio, Yusuke Okuno, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

Successful Therapy with Ascites Drainage and Defibrotide for Veno-Occlusive Disease Developed after Bone Marrow Transplantation in Acute Lymphoblastic Leukemia

Ryo Maemura, Atsushi Narita, Shinsuke Kataoka, Rieko Taniguchi, Motoharu Hamada, Eri Nishikawa, Nozomu Kawashima, Nobuhiro Nishio, Hideki Muramatsu, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 68 2021.11

がん遺伝子パネル検査でBRAF V600E変異を認めた副腎腫瘍の16歳女性

佐治木大知, 村松秀城, 津村悠介, 前村遼, 今屋雅之, 山森彩子, 若松学, 吉田太郎, 三輪田俊介, 成田幸太郎, 市川大輔, 濱田太立, 谷口理恵子, 鈴木喬悟, 川島希, 西川英里, 成田敦, 西尾信博, 高橋義行, 島田聡子, 榊原綾子, 下山芳江, 岩淵英人

日本小児血液・がん学会雑誌 Vol. 58 ( 3 ) page： 325 - 326 2021.11

Hematopoietic stem cell transplantation for infants with high-risk KMT2A gene-rearranged acute lymphoblastic leukemia. International journal Open Access

Takayuki Takachi, Tomoyuki Watanabe, Takako Miyamura, Akiko Moriya Saito, Takao Deguchi, Toshinori Hori, Tomomi Yamada, Shigeru Ohmori, Masami Haba, Yuki Aoki, Sae Ishimaru, Shinya Sasaki, Junjiro Ohshima, Akihiro Iguchi, Yoshiyuki Takahashi, Nobuyuki Hyakuna, Atsushi Manabe, Keizo Horibe, Eiichi Ishii, Katsuyoshi Koh, Daisuke Tomizawa

Blood advances Vol. 5 ( 19 ) page： 3891 - 3899 2021.10

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

The role of allogeneic hematopoietic stem cell transplantation (HSCT) for infants with acute lymphoblastic leukemia (ALL) and KMT2A gene rearrangement (KMT2A-r) is controversial in terms of both its efficacy and potential for acute and late toxicities. In Japanese Pediatric Leukemia/Lymphoma Study Group trial MLL-10, by introducing intensive chemotherapy, indication of HSCT was restricted to patients with high-risk (HR) features only (KMT2A-r and either age <180 days or presence of central nervous system leukemia). Of the 56 HR patients, 49 achieved complete remission. Forty-three patients received HSCT in first remission including 38 patients receiving protocol-specified HSCT with conditioning consisting of individualized targeted doses of busulfan, etoposide, and cyclophosphamide. Three-year event-free survival (EFS) of 56.8% (95% confidence interval [CI], 42.4% to 68.8%) and overall survival of 80.2% (95% CI, 67.1% to 88.5%) were accomplished. Univariable analysis showed that Interfant-HR criteria and flow cytometric minimal residual disease (MRD; ≥0.01%), both at the end of induction and at the end of consolidation (EOC), were significantly associated with poorer EFS. In the multivariable analysis, positive MRD at EOC was solely associated with poor EFS (P < .001). Rapid pretransplant MRD clearance and tailored HSCT strategy in the MLL-10 trial resulted in a favorable outcome for infants with HR KMT2A-r ALL. However, considering the high rate of potentially life-threatening toxicities and the risk of late effects, its indication should be further restricted or even eliminated in the future by introducing more effective therapeutic modalities with minimal toxicities. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.

DOI： 10.1182/bloodadvances.2020004157

Usefulness of functional splicing analysis to confirm precise disease pathogenesis in Diamond-Blackfan anemia caused by intronic variants in RPS19 Open Access

Single-Arm Non-Blinded Multicenter Clinical Trial on T-Cell-Replete Haploidentical Stem Cell Transplantation Using Low-Dose Antithymocyte Globulin for Relapsed and Refractory Pediatric Acute Leukemia.

Kada A, Kikuta A, Saito AM, Kato K, Iguchi A, Yabe H, Ishida H, Hyakuna N, Takahashi Y, Nagasawa M, Hashii Y, Umeda K, Matsumoto K, Fujisaki H, Yano M, Nakazawa Y, Sano H

The Kurume medical journal Vol. 66 ( 3 ) page： 161 - 168 2021.10

Clinical Images: Extensive multiple organ involvement in VEXAS syndrome Open Access

Takahashi, N; Takeichi, T; Nishida, T; Sato, J; Takahashi, Y; Yamamura, M; Ogi, T; Akiyama, M

ARTHRITIS & RHEUMATOLOGY Vol. 73 ( 10 ) page： 1896 - 1897 2021.10

Acquisition of a rare NUP98-BPTF fusion gene associated with recurrence of acute myeloid leukemia. International journal

Koji Kawaguchi, Shohei Azumi, Yosuke Itakura, Takayuki Takachi, Taemi Ogura, Yasuo Horikoshi, Kyogo Suzuki, Hideki Muramatsu, Asahito Hama, Yoshiyuki Takahashi, Kenichiro Watanabe

Pediatric blood & cancer Vol. 68 ( 10 ) page： e29201 2021.10

腹水ドレナージとデフィブロタイドが奏功した急性リンパ性白血病に対する骨髄移植後Veno-Occlusive Disease(Successful Therapy with Ascites Drainage and Defibrotide for Veno-Occlusive Disease Developed After Bone marrow Transplantation in Acute Lymphoblastic Leukemia)

Maemura Ryo, Narita Atsushi, Kataoka Shinsuke, Taniguchi Rieko, Hamada Motoharu, Nishikawa Eri, Kawashima Nozomu, Nishio Nobuhiro, Muramatsu Hideki, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 58 ( 4 ) page： 246 - 246 2021.10

神経芽腫における尿中バイオマーカー(Urinary biomarkers predicting treatment outcomes in neuroblastoma)

Narita Atsushi, Hinoki Akinari, Yokota Kazuki, Hamada Motoharu, Kataoka Shinsuke, Kawashima Nozomu, Muramatsu Hideki, Nishio Nobuhiro, Uchida Hiroo, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 58 ( 4 ) page： 225 - 225 2021.10

小児骨髄不全症候群コホート中のFPD-MMが疑われたRUNX1変異10症例のまとめ(Ten patients with RUNX1 mutation who were suspected with FPD-MM in a pediatric cohort of inherited bone marrow failure syndrome)

Yamamori Ayako, Hamada Motoharu, Muramatsu Hideki, Taniguchi Rieko, Kataoka Shinsuke, Kawashima Nozomu, Narita Atsushi, Nishio Nobuhiro, Okuno Yusuke, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 58 ( 4 ) page： 214 - 214 2021.10

小児同種移植後に長期入院を要する原因と移植後晩期にみられる消化管合併症(Prolonged Hospitalization and Late Gastroenterological Complications in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation)

Kawashima Nozomu, Kataoka Shinsuke, Hamada Motoharu, Nishikawa Eri, Taniguchi Rieko, Narita Atsushi, Muramatsu Hideki, Nishio Nobuhiro, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 58 ( 4 ) page： 242 - 242 2021.10

化学療法による治療介入を行った生後2ヵ月未満発症の神経芽腫4S(Using chemotherapy to treat neuroblastoma stage 4S with hepatomegaly in a patient younger than 2 months old)

Imaya Masayuki, Nishio Nobuhiro, Taniguchi Rieko, Kataoka Shinsuke, Hamada Motoharu, Nishikawa Eri, Kawashima Nozomu, Narita Atsushi, Muramatsu Hideki, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 58 ( 4 ) page： 225 - 225 2021.10

単一施設における再発4期神経芽腫に対するKIRリガンド不一致同種臍帯血移植による治療成績(Outcomes of KIR-ligand incompatible allogeneic cord blood transplantation for relapsed stage 4 neuroblastoma: a single institutional study)

Kataoka Shinsuke, Nishio Nobuhiro, Wakamatsu Manabu, Taniguchi Rieko, Nishikawa Eri, Hamada Motoharu, Kawashima Nozomu, Narita Atsushi, Muramatsu Hideki, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 58 ( 4 ) page： 226 - 226 2021.10

小児における未分化白血病の臨床的特徴(Clinical features of immature leukemias in children)

Sajiki Daichi, Yoshida Nao, Muramatsu Hideki, Sakaguchi Kimiyoshi, Maeda Naoko, Yokoyama Norifumi, Miyajima Yuji, Tanaka Makito, Takahashi Yoshiyuki, Hama Asahito

日本小児血液・がん学会雑誌 Vol. 58 ( 4 ) page： 185 - 185 2021.10

NGS-MRDに基づくリスク層別化による高リスクALLに対する治療強化(Strategy of intensified therapy for high risk pediatric acute lymphoblastic leukemia based on NGS-MRD-based risk stratification)

Hamada Motoharu, Imaya Masayuki, Okuno Yusuke, Kawashima Nozomu, Taniguchi Rieko, Narita Atsushi, Muramatsu Hideki, Nishio Nobuhiro, Hasegawa Shinji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 58 ( 4 ) page： 191 - 191 2021.10

CD19-CAR-T細胞療法後に再発したB-ALLに対するCD19-CAR-T細胞の再投与(Re-treatment with CD19-targeted CAR-T cells for relapse after CD19-CAR-T cell therapy)

Nishio Nobuhiro, Hamada Motoharu, Nishikawa Eri, Kawashima Nozomu, Narita Atsushi, Muramatsu Hideki, Wang Kai, Zheng Huyong, Chang Jung-Li, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 58 ( 4 ) page： 191 - 191 2021.10

Takafuji, S; Mori, T; Nishimura, N; Yamamoto, N; Uemura, S; Nozu, K; Terui, K; Toki, T; Ito, E; Muramatsu, H; Takahashi, Y; Matsuo, M; Yamamura, T; Iijima, K

PEDIATRIC HEMATOLOGY AND ONCOLOGY Vol. 38 ( 6 ) page： 515 - 527 2021.9

Clinical diagnostic value of telomere length measurement in inherited bone marrow failure syndromes. International journal Open Access

Shunsuke Miwata, Atsushi Narita, Yusuke Okuno, Kyogo Suzuki, Motoharu Hamada, Taro Yoshida, Masayuki Imaya, Ayako Yamamori, Manabu Wakamatsu, Kotaro Narita, Hironobu Kitazawa, Daisuke Ichikawa, Rieko Taniguchi, Nozomu Kawashima, Eri Nishikawa, Nobuhiro Nishio, Seiji Kojima, Hideki Muramatsu, Yoshiyuki Takahashi

Haematologica Vol. 106 ( 9 ) page： 2511 - 2515 2021.9

Autoantibodies against the plakin family proteins as a novel marker for chronic graft-versus-host disease of the lung. International journal Open Access

Nozomu Kawashima, Eri Nishikawa, Atsunari Tsuchisaka, Takashi Hashimoto, Yusuke Okuno, Motoharu Hamada, Daisuke Ichikawa, Atsushi Narita, Hideki Muramatsu, Nobuhiro Nishio, Seiji Kojima, Yoshinao Muro, Yoshiyuki Takahashi

Bone marrow transplantation Vol. 56 ( 9 ) page： 2291 - 2294 2021.9

Echocardiography Monitoring of Pulmonary Hypertension after Pediatric Hematopoietic Stem Cell Transplantation: Pediatric Pulmonary Arterial Hypertension and Pulmonary Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation. International journal Open Access

Nozomu Kawashima, Yoshie Fukasawa, Eri Nishikawa, Keiko Ohta-Ogo, Hatsue Ishibashi-Ueda, Motoharu Hamada, Daisuke Ichikawa, Atsushi Narita, Yusuke Okuno, Hideki Muramatsu, Nobuhiro Nishio, Seiji Kojima, Taichi Kato, Yoshiyuki Takahashi

Transplantation and cellular therapy Vol. 27 ( 9 ) page： 786.e1 - 786.e8 2021.9

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

Pulmonary hypertension (PH) is associated with high morbidity in children undergoing hematopoietic stem cell transplantation (HSCT). However, owing to the lack of sequential echocardiography, the nature of the condition is not fully understood. This study was conducted to investigate whether routine echocardiography performed after HSCT could detect patients with PH at an earlier stage and elucidate the role of intervention using tadalafil. The study population comprised 93 consecutive children age <18 years who underwent a total of 109 HSCTs. All patients underwent routine transthoracic echocardiography during HSCT. Four children (4%) with a median age of 4 years (range, 0.7 to 6 years) were found to have PH, and their median tricuspid regurgitation peak velocity (TRV) was 4.1 m/s (range, 3.5 to 4.2 m/s). PH was diagnosed at a median of 52 days (range, 21 to 118 days) after HSCT. Three of them were diagnosed with neuroblastoma, and 1 was diagnosed with infantile leukemia. One patient developed PH after autologous HSCT, and 3 received killer immunoglobulin-like receptor ligand-mismatched cord blood. Busulfan was used for conditioning in all patients, and the proportion of patients receiving this medication was significantly higher in the PH group compared with the non-PH group (100% versus 30%; P = .011). Three of the 4 patients had a durable response (TRV ≤2.8 m/s) at a median of 46 days (range, 14 to 79 days) after starting treatment with tadalafil. No patient experienced exacerbation of PH, and treatment was completed at median of 96 days (range, 46 to 212 days). Our data suggest that routine echocardiography monitoring after HSCT should be considered in children receiving busulfan, although the precise follow-up timing needs further study. In addition, safe and effective administration of tadalafil must be ensured by close monitoring.

DOI： 10.1016/j.jtct.2021.05.017

Effect of high-dose chemotherapy plus stem cell rescue on the survival of patients with neuroblastoma modified by MYCN gene gain/amplification and remission status: a nationwide registration study in Japan. International journal

Yuya Saito, Mitsuyoshi Urashima, Yoshiyuki Takahashi, Atsushi Ogawa, Chikako Kiyotani, Yuki Yuza, Katsuyoshi Koh, Kenichiro Watanabe, Yoshiyuki Kosaka, Hiroaki Goto, Atsushi Kikuta, Keiko Okada, Yuhki Koga, Junya Fujimura, Masami Inoue, Atsushi Sato, Yoshiko Atsuta, Kimikazu Matsumoto

Bone marrow transplantation Vol. 56 ( 9 ) page： 2173 - 2182 2021.9

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

In high-risk neuroblastoma, the presence of an MYCN gain/amplification (MYCN-GA) is not always a risk factor of cancer-specific death. We herein examined the effect modification of high-dose chemotherapy with autologous hematopoietic stem cell rescue (HDC-autoSCR) in terms of the interaction between MYCN status and remission status (complete remission or very good partial remission [CR/VGPR] vs. partial remission or less [≤PR]). The present study recruited patient data from 1992 to 2017 in the Japan Society of Hematopoietic Cell Transplantation's national registry. The MYCN status was known in 586 of 950 patients with a single course of HDC-autoSCR. Cumulative hazard curves for neuroblastoma-specific death showed that a subgroup with MYCN-GA and ≤PR had a significantly poorer prognosis than three other subgroups, namely, the MYCN-NGA/ ≤ PR, MYCN-NGA/CR/VGPR, and MYCN-GA/CR/VGPR subgroups even after adjusting for non-infants and stage IV disease (hazard ratio: 2.79; 95% confidence interval: 1.91-4.09; P < 0.001). The interaction between MYCN-GA and ≤PR was significant (pinteraction = 0.006). Hence, the patients with MYCN-GA with non-remission status at HDC-autoSCR had a significantly poorer prognosis than the other subgroups, suggesting that HDC-autoSCR may be effective in patients with CR/VGPR regardless of MYCN gene status and in patients with MYCN-NGA regardless of remission status.

DOI： 10.1038/s41409-021-01303-z

急性リンパ性白血病に対するpiggyBacトランスポゾン法によるCD19 CAR-T療法の臨床第I相試験(Phase I study of piggyBac transposon mediated CD19: CAR-T therapy for acute lymphoblastic leukemia)

西尾信博, 葉名尻良, 石川裕一, 寺倉精太郎, 西田徹也, 村田誠, 濱田太立, 西川英里, 川島希, 奥野友介, 成田敦, 村松秀城, 高橋義行

日本血液学会学術集会 Vol. 83回 page： OS2 - 4 2021.9

Revesz syndrome with severe pancytopenia and bilateral retinal detachment: A case report(和訳中)

山森彩子, 津村悠介, 前村遼, 今屋雅之, 若松学, 三輪田俊介, 吉田太郎, 成田幸太郎, 谷口理恵子, 濱田太立, 鈴木喬悟, 西川英里, 川島希, 成田敦, 村松秀城, 奥野友介, 西尾信博, 小島勢二, 高橋義行

日本血液学会学術集会 Vol. 83回 page： PS - 4 2021.9

Phase I study of piggyBac transposon mediated CD19: CAR-T therapy for acute lymphoblastic leukemia(和訳中)

西尾信博, 葉名尻良, 石川裕一, 寺倉精太郎, 西田徹也, 村田誠, 濱田太立, 西川英里, 川島希, 奥野友介, 成田敦, 村松秀城, 高橋義行

日本血液学会学術集会 Vol. 83回 page： OS2 - 4 2021.9

Prospective validation of the provisional entity of RCC proposed by the WHO(和訳中)

濱麻人, 真部淳, 長谷川大輔, 野沢和江, 成田敦, 村松秀城, 高橋義行, 渡邉健一郎, 小原明, 伊藤雅文, 小島勢二

日本血液学会学術集会 Vol. 83回 page： OS1 - 2 2021.9

HLA one-allele mismatched unrelated BMT using antithymocyte globulin in Japanese pediatric patients(和訳中)

濱田太立, 村松秀城, 吉田太郎, 今屋雅之, 山森彩子, 三輪田俊介, 成田幸太郎, 鈴木喬悟, 川島希, 谷口理恵子, 西川英里, 成田敦, 西尾信博, 高橋義行

日本血液学会学術集会 Vol. 83回 page： OS1 - 4 2021.9

Blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia(和訳中)

成田敦, 佐治木大知, 津村悠介, 前村遼, 今屋雅之, 山森彩子, 若松学, 谷口理恵子, 濱田太立, 片岡伸介, 西川英里, 川島希, 奥野友介, 村松秀城, 西尾信博, 高橋義行

日本血液学会学術集会 Vol. 83回 page： OS1 - 2 2021.9

A mutation in a proteasome subunit depletes its activities leading to excessive interferon signaling(和訳中)

川島希, 片岡伸介, 村松秀城, 大西秀典, 奥野友介, 今屋雅之, 山森彩子, 若松学, 濱田太立, 西川英里, 成田敦, 西尾信博, 小島勢二, 高橋義行

日本血液学会学術集会 Vol. 83回 page： OS1 - 5 2021.9

Relationship between plasma rabbit anti-thymocyte globulin concentration and immunosuppressive therapy response in patients with severe aplastic anemia. International journal

Atsushi Narita, Hideki Muramatsu, Daisuke Ichikawa, Motoharu Hamada, Eri Nishikawa, Kyogo Suzuki, Nozomu Kawashima, Yusuke Okuno, Nobuhiro Nishio, Asahito Hama, Hirohito Yamazaki, Shinji Nakao, Seiji Kojima, Yoshiyuki Takahashi

European journal of haematology Vol. 107 ( 2 ) page： 255 - 264 2021.8

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

OBJECTIVES: Patients with acquired aplastic anemia (AA) without HLA-matched sibling donors or aged >40 years receive immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG). We investigated the relationship between plasma rabbit ATG (r-ATG) concentration and IST response. METHODS: From May 2012 to October 2017, 81 patients with severe AA who required initial IST were included. A 1:1 block randomization was employed for 2.5 and 3.5 mg/kg doses of r-ATG. RESULTS: No significant difference in response rates was observed between the 2.5 and 3.5 mg/kg groups (63% vs. 58%, P = .894). Median r-ATG concentrations on days 14 and 28 after IST were 15.2 (0.0-97.7) and 1.8 (0.0-74.9 µg/mL), respectively. According to r-ATG concentration, response rates were significantly higher in the group with higher r-ATG concentration than in those with lower r-ATG concentration (day 14, 88% vs. 52%; P = .006 and day 28, 79% vs. 46%; P = .005). In multivariate analysis, higher r-ATG concentrations at day 28 were independent predictors of favorable response to IST at 6 months (odds ratio, 0.29; 95% confidence interval, 0.09-0.93; P = .037). CONCLUSIONS: The present data indicate that higher r-ATG concentration at day 28 resulted in improved IST response.

DOI： 10.1111/ejh.13644

Successful treatment of a novel type I interferonopathy due to a de novo PSMB9 gene mutation with a Janus kinase inhibitor Open Access

Shinsuke Kataoka, Nozomu Kawashima, Yusuke Okuno, Hideki Muramatsu, Shunsuke Miwata, Kotaro Narita, Motoharu Hamada, Norihiro Murakami, Rieko Taniguchi, Daisuke Ichikawa, Hironobu Kitazawa, Kyogo Suzuki, Eri Nishikawa, Atsushi Narita, Nobuhiro Nishio, Hidenori Yamamoto, Yoshie Fukasawa, Taichi Kato, Hiroyuki Yamamoto, Jun Natsume, Seiji Kojima, Ichizo Nishino, Takeshi Taketani, Hidenori Ohnishi, Yoshiyuki Takahashi

Journal of Allergy and Clinical Immunology Vol. 148 ( 2 ) page： 639 - 644 2021.8

Repetitive sleep starts: An important differential diagnosis of infantile spasms. International journal

Yuki Maki, Hiroyuki Kidokoro, Akihisa Okumura, Hiroyuki Yamamoto, Tomohiko Nakata, Tatsuya Fukasawa, Tetsuo Kubota, Masahiro Kawaguchi, Takeshi Suzuki, Masaharu Tanaka, Yu Okai, Yoko Sakaguchi, Atsuko Ohno, Tamiko Negoro, Yoshiyuki Takahashi, Jun Natsume

Epilepsy & behavior : E&B Vol. 121 ( Pt A ) page： 108075 - 108075 2021.8

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

OBJECTIVE: Repetitive sleep starts (RSS) are clusters of nonepileptic, spasm-like movements occurring during sleep onset. However, their characteristics have yet to be defined. We conducted a clinicoelectroencephalographic study of children with RSS to clarify their detailed characteristics. METHODS: To differentiate starts from epileptic spasms, we recruited children with brief "crescendo-decrescendo" muscle contractions that simultaneously involved the limbs and trunk without electroencephalogram changes, and that fulfilled the following criteria: (1) repeated occurrence (five or more) and (2) manifestation during sleep stage N1-N2. A total of nine children met these criteria. Their clinical information and video-electroencephalogram data were analyzed retrospectively. RESULTS: The background conditions observed at onset of RSS were perinatal hypoxic-ischemic encephalopathy (n = 4), West syndrome of unknown etiology (n = 1), and traumatic brain injury (n = 1). The age at onset of RSS, the number of starts in a given RSS cluster, the interval between starts, and the duration of surface electromyogram activity were between 3 and 46 months, 5 and 547, <1 and 60 s, and 0.3 and 5.4 s, respectively. None of the median value of these parameters differed between children with and without corticospinal tract injury. During the median follow-up period of 33 months, RSS disappeared spontaneously in five. CONCLUSION: This is the largest case series of RSS clarifying their clinicoelectroencephalographic characteristics reported to date. To avoid unnecessary antiepileptic therapies, clinicians should be aware of RSS and distinguish it from other disorders involving involuntary movements or seizures, especially epileptic spasms.

DOI： 10.1016/j.yebeh.2021.108075

Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy Open Access

Suzuki, T; Sato, Y; Kushida, Y; Tsuji, M; Wakao, S; Ueda, K; Imai, K; Iitani, Y; Shimizu, S; Hida, H; Temma, T; Saito, S; Iida, H; Mizuno, M; Takahashi, Y; Dezawa, M; Borlongan, CV; Hayakawa, M

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Vol. 41 ( 7 ) page： 1707 - 1720 2021.7

小児におけるcord colitis syndromeの臨床的・病理学的特徴

前村遼, 成田敦, 濱田太立, 鈴木喬悟, 西川英里, 川島希, 奥野友介, 西尾信博, 村松秀城, 伊藤雅文, 高橋義行

臨床血液 Vol. 62 ( 7 ) page： 863 - 863 2021.7

Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas. International journal Open Access

Daisuke Ichikawa, Kyoko Yamashita, Yusuke Okuno, Hideki Muramatsu, Norihiro Murakami, Kyogo Suzuki, Daiei Kojima, Shinsuke Kataoka, Motoharu Hamada, Rieko Taniguchi, Eri Nishikawa, Nozomu Kawashima, Atsushi Narita, Nobuhiro Nishio, Asahito Hama, Kenji Kasai, Seiji Mizuno, Yoshie Shimoyama, Masato Nakaguro, Hajime Okita, Seiji Kojima, Atsuko Nakazawa, Yoshiyuki Takahashi

NPJ genomic medicine Vol. 6 ( 1 ) page： 49 - 49 2021.6

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

Pediatric solid tumors are a heterogeneous group of neoplasms with over 100 subtypes. Clinical and histopathological diagnosis remains challenging due to the overlapping morphological and immunohistochemical findings and the presence of atypical cases. To evaluate the potential utility of including RNA-sequencing (RNA-seq) in the diagnostic process, we performed RNA-seq in 47 patients with suspected pediatric sarcomas. Histopathologists specialized in pediatric cancer re-evaluated pathological specimens to reach a consensus diagnosis; 42 patients were diagnosed with known subtypes of solid tumors whereas 5 patients were diagnosed with undifferentiated sarcoma. RNA-seq analysis confirmed and refined consensus diagnoses and further identified diagnostic genetic variants in four of the five patients with undifferentiated sarcoma. Genetic lesions were detected in 23 patients, including the novel SMARCA4-THOP1 fusion gene and 22 conventional or recently reported genetic events. Unsupervised clustering analysis of the RNA-seq data identified a distinct cluster defined by the overexpression of rhabdomyosarcoma-associated genes including MYOG and CHRNG. These findings suggest that RNA-seq-based genetic analysis may aid in the diagnosis of suspected pediatric sarcomas, which would be useful for the development of stratified treatment strategies.

DOI： 10.1038/s41525-021-00210-y

Age estimates from brain magnetic resonance images of children younger than two years of age using deep learning

Kawaguchi, M; Kidokoro, H; Ito, R; Shiraki, A; Suzuki, T; Maki, Y; Tanaka, M; Sakaguchi, Y; Yamamoto, H; Takahashi, Y; Naganawa, S; Natsume, J

MAGNETIC RESONANCE IMAGING Vol. 79 page： 38 - 44 2021.6

A Phase 2 Open-label, Single-arm, Multicenter Study of Ruxolitinib Added to Corticosteroids in Pediatric Subjects with Moderate/Severe Chronic Gvhd After Allogeneic Stem Cell Transplantation (REACH5)

Wall, D; Koh, K; Bhat, S; Takahashi, Y; Zhang, A; Rosko, C; Smith, Y; Stefanelli, T; Diaz-de-Heredia, C; Locatelli, F

BONE MARROW TRANSPLANTATION Vol. 56 ( SUPPL 1 ) page： 228 - 229 2021.6

診断および治療に難渋している、脳を含む全身性多発転移腫瘤を有する先天性肉腫の乳児

今屋雅之, 川島希, 山森彩子, 若松学, 吉田太郎, 三輪田俊介, 成田幸太郎, 北澤宏展, 谷口理恵子, 市川大輔, 濱田太立, 西川英里, 成田敦, 奥野友介, 村松秀城, 西尾信博, 小島勢二, 高橋義行, 中村栄男, 孝橋賢一, 大喜多肇

日本小児血液・がん学会雑誌 Vol. 58 ( 1 ) page： 60 - 60 2021.6

がん遺伝子パネル検査でGOPC-ROS1 fusionを認めた中枢神経胎児性腫瘍の0歳児症例

夏目敦至, 栗本路弘, 芝良樹, 青木恒介, 若林俊彦, 川島希, 谷口理恵子, 村松秀城, 高橋義行, 高野桂, 榊原綾子, 下山芳江, 中村栄男, 森田佐知, 安藤雄一, 平戸純子

日本小児血液・がん学会雑誌 Vol. 58 ( 1 ) page： 61 - 61 2021.6

Urinary biomarkers for monitoring treatment response in neuroblastoma patients.

Amano, H; Hinoki, A; Uchida, H; Yokota, K; Ishigaki, T; Sakairi, M; Abe, M; Takahashi, Y; Narita, A; Tainaka, T; Shirota, C; Sumida, W; Makita, S; Takimoto, A; Kano, Y; Yasui, A; Okamoto, M; Nakagawa, Y

JOURNAL OF CLINICAL ONCOLOGY Vol. 39 ( 15 ) 2021.5

Whole genome sequencing of 45 Japanese patients with intellectual disability Open Access

Abe-Hatano, C; Iida, A; Kosugi, S; Momozawa, Y; Terao, C; Ishikawa, K; Okubo, M; Hachiya, Y; Nishida, H; Nakamura, K; Miyata, R; Murakami, C; Takahashi, K; Hoshino, K; Sakamoto, H; Ohta, S; Kubota, M; Takeshita, E; Ishiyama, A; Nakagawa, E; Sasaki, M; Kato, M; Matsumoto, N; Kamatani, Y; Kubo, M; Takahashi, Y; Natsume, J; Inoue, K; Goto, YI

AMERICAN JOURNAL OF MEDICAL GENETICS PART A Vol. 185 ( 5 ) page： 1468 - 1480 2021.5

Reduced-intensity conditioning is effective for hematopoietic stem cell transplantation in young pediatric patients with Diamond–Blackfan anemia

Shun Koyamaishi, Takuya Kamio, Akie Kobayashi, Tomohiko Sato, Ko Kudo, Shinya Sasaki, Rika Kanezaki, Daiichiro Hasegawa, Hideki Muramatsu, Yoshiyuki Takahashi, Yoji Sasahara, Hidefumi Hiramatsu, Harumi Kakuda, Miyuki Tanaka, Masataka Ishimura, Masanori Nishi, Akira Ishiguro, Hiromasa Yabe, Takeo Sarashina, Masaki Yamamoto, Yuki Yuza, Nobuyuki Hyakuna, Kenichi Yoshida, Hitoshi Kanno, Shouichi Ohga, Akira Ohara, Seiji Kojima, Satoru Miyano, Seishi Ogawa, Tsutomu Toki, Kiminori Terui, Etsuro Ito

Bone Marrow Transplantation Vol. 56 ( 5 ) page： 1013 - 1020 2021.5

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

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for the hematologic manifestations of Diamond–Blackfan anemia (DBA). However, data regarding the optimal conditioning regimen for DBA patients are limited. We retrospectively compared the outcomes of DBA patients who underwent HSCT using either myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens. The patients belonged to a cohort treated at our hospitals between 2000 and 2018. HSCT was performed in 27 of 165 patients (16.4%). The median age at the time of HSCT was 3.6 years. Stem cell sources included bone marrow for 25 patients (HLA-matched sibling donors, n = 5; HLA-mismatched related donors, n = 2; HLA-matched/mismatched unrelated donors, n = 18) or cord blood for 2 patients. MAC or RIC regimens were used in 12 and 15 patients, respectively. Engraftment was successful in all 27 patients who underwent HSCT. Three patients who underwent HSCT using MAC regimens developed sinusoidal obstruction syndrome. The 3-year overall survival (OS) and failure-free survival rates (FFS) post-transplantations were 95.2% and 88.4%, respectively, with no significant differences between MAC and RIC regimens. Our data suggest that HSCTs using RIC regimens are effective and obtain engraftment with excellent OS and FFS for young DBA patients.

DOI： 10.1038/s41409-020-01056-1

Scopus

Correction: Reduced-intensity conditioning is effective for hematopoietic stem cell transplantation in young pediatric patients with Diamond-Blackfan anemia (Bone Marrow Transplantation, (2021), 56, 5, (1013-1020), 10.1038/s41409-020-01056-1) Open Access

Bone Marrow Transplantation Vol. 56 ( 5 ) page： 1218 - 1219 2021.5

Temporal dynamics of the plasma microbiome in recipients at early post-liver transplantation: a retrospective study. International journal Open Access

Toshihiko Okumura, Kazuhiro Horiba, Hideya Kamei, Suguru Takeuchi, Takako Suzuki, Yuka Torii, Jun-Ichi Kawada, Yoshiyuki Takahashi, Yasuhiro Ogura, Tomoo Ogi, Yoshinori Ito

BMC microbiology Vol. 21 ( 1 ) page： 104 - 104 2021.4

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

BACKGROUND: Immunosuppression during liver transplantation (LT) enables the prevention and treatment of organ rejection but poses a risk for severe infectious diseases. Immune modulation and antimicrobials affect the plasma microbiome. Thus, determining the impact of immunosuppression on the microbiome may be important to understand immunocompetence, elucidate the source of infection, and predict the risk of infection in LT recipients. We characterized the plasma microbiome of LT recipients at early post-LT and assessed the association between the microbiome and clinical events. RESULTS: In this study, 51 patients who received LT at Nagoya University Hospital from 2016 to 2018 were enrolled. Plasma samples were retrospectively collected at the following time points: 1) within a week after LT; 2) 4 ± 1 weeks after LT; 3) 8 ± 1 weeks after LT; and 4) within 2 days after a positive blood culture. A total of 111 plasma samples were analyzed using shotgun next-generation sequencing (NGS) with the PATHDET pipeline. Relative abundance of Anelloviridae, Nocardiaceae, Microbacteriaceae, and Enterobacteriaceae significantly changed during the postoperative period. Microbiome diversity was higher within a week after LT than that at 8 weeks after LT. Antimicrobials were significantly associated with the microbiome of LT recipients. In addition, the proportion of Enterobacteriaceae was significantly increased and the plasma microbiome diversity was significantly lower in patients with acute cellular rejection (ACR) than non-ACR patients. Sequencing reads of bacteria isolated from blood cultures were predominantly identified by NGS in 8 of 16 samples, and human herpesvirus 6 was detected as a causative pathogen in one recipient with severe clinical condition. CONCLUSIONS: The metagenomic NGS technique has great potential in revealing the plasma microbiome and is useful as a comprehensive diagnostic procedure in clinical settings. Temporal dynamics of specific microorganisms may be used as indirect markers for the determination of immunocompetence and ACR in LT recipients.

DOI： 10.1186/s12866-021-02154-w

Hippocampal Atrophy in Pediatric Transplant Recipients with Human Herpesvirus 6B. International journal Open Access

Misa Miyake, Yoshiki Kawamura, Naoko Ishihara, Shigetaka Suzuki, Hiroki Miura, Yoko Sakaguchi, Masaharu Tanaka, Yoshiyuki Takahashi, Seiji Kojima, Hiroshi Toyama, Jun Natsume, Tetsushi Yoshikawa

Microorganisms Vol. 9 ( 4 ) 2021.4

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

The aim of this study was to determine whether human herpesvirus 6B (HHV-6B) infection can impair the hippocampus in pediatric hematopoietic stem cell transplant (HSCT) recipients. Study subjects were pediatric HSCT recipients monitored for HHV-6B infection who underwent brain MRI before and after transplantation. Volumetric analysis of the hippocampus was performed. Of the 107 patients that received HSCT at Nagoya University Hospital Between July 2008 and April 2014, 20 were eligible for volumetric analysis. Eight patients had HHV-6B infection, of whom two had encephalopathy at the time of HHV-6B infection. None of the 12 patients without HHV-6B infection had encephalopathy. The median ratio of the right hippocampal volume from before to after transplantation was 0.93 in patients with HHV-6B infection and 1.02 in without HHV-6B infection (p = 0.007). The median ratio of the left hippocampal volume ratio in patients with and without HHV-6B infection was 0.92 and 1.00, respectively (p = 0.003). Among the eight patients with HHV-6B infection, four had a marked reduction in hippocampal volume (volume ratio < 0.90). Only one of these patients had neurological symptoms at the time of HHV-6B infection. The reduction in the hippocampal volume ratio was higher in pediatric HSCT recipients with HHV-6B infection than those without viral infection. Neurological follow-up may be required for pediatric HSCT recipients with HHV-6B infection.

DOI： 10.3390/microorganisms9040776

Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation Open Access

Goto, T; Murata, M; Nishida, T; Terakura, S; Kamoshita, S; Ishikawa, Y; Ushijima, Y; Adachi, Y; Suzuki, S; Kato, K; Hirakawa, A; Nishiwaki, S; Nishio, N; Takahashi, Y; Kodera, Y; Matsushita, T; Kiyoi, H

STEM CELLS TRANSLATIONAL MEDICINE Vol. 10 ( 4 ) page： 542 - 553 2021.4

Phosphorylated proteome analysis of a novel germline ABL1 mutation causing an autosomal dominant syndrome with ventricular septal defect. International journal

Hidenori Yamamoto, Satoshi Hayano, Yusuke Okuno, Atsuto Onoda, Kohji Kato, Noriko Nagai, Yoshie Fukasawa, Shinji Saitoh, Yoshiyuki Takahashi, Taichi Kato

International journal of cardiology Vol. 326 page： 81 - 87 2021.3

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

BACKGROUND: A gain-of-function mutation in germline ABL1 causes a syndrome including congenital heart defects. However, the molecular mechanisms of this syndrome remain unknown. In this study, we found a novel ABL1 mutation in a Japanese family with ventricular septal defect, finger contracture, skin abnormalities and failure to thrive, and the molecular mechanisms of these phenotypes were investigated. METHODS AND RESULTS: Whole-exome sequencing on several family members revealed a novel mutation (c.1522A > C, p.I508L) in the tyrosine kinase domain of ABL1, and complete co-segregation with clinical presentations was confirmed in all members. Wild-type and mutant ABL1 were transfected into human embryonic kidney 293 cells for functional analysis. Western blotting confirmed that tyrosine phosphorylation in STAT5, a substrate of ABL1, was enhanced, and the novel mutation was proved to be a gain-of-function mutation. Since this novel mutation in ABL1 enhances tyrosine kinase activity, phosphorylated proteome analysis was used to elucidate the molecular pathology. The proteome analysis showed that phosphorylation in proteins such as UFD1, AXIN1, ATRX, which may be involved in the phenotypes, was enhanced in the mutant group. CONCLUSIONS: The onset of congenital heart defects associated with this syndrome appears to involve a mechanism caused by UFD1 common to 22q.11.2 deletion syndrome. On the other hand, AXIN1 and ATRX may be important in elucidating the mechanisms of other phenotypes, such as finger contracture and failure to thrive. Verification of these hypotheses would lead to further understanding of the pathophysiology and the development of treatment methods.

DOI： 10.1016/j.ijcard.2020.10.032

Initial treatment of seizures in children in an emergency department in rural Japan. International journal

Anna Shiraki, Masahiro Yasui, Hiroyuki Kidokoro, Shinji Kido, Hideo Ando, Yoshiyuki Takahashi, Jun Natsume

Brain & development Vol. 43 ( 2 ) page： 288 - 293 2021.2

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

OBJECTIVE: Although the initial treatment of childhood seizures is important, treatment within an appropriate time window is often difficult in resource-limited areas. This study examined childhood seizure treatment in a rural area in Japan. METHODS: We retrospectively investigated children presenting to Nakatsugawa Municipal General Hospital emergency department between 2015 and 2018. From the hospital database, we identified children who were diagnosed with seizures, epilepsy, or acute infectious encephalitis/encephalopathy or were given benzodiazepines. We considered etiology, seizure duration, and treatment according to the specialties of the doctors providing initial care. RESULTS: We extracted 236 seizure events: 40 initially treated by pediatricians, 16 by a mobile doctor team, and 180 by other doctors. Twenty patients had continuous seizures for longer than 5 min on admission. Two were treated by pediatricians at presentation; it took 4 and 7 min after arrival to stop the seizures. Four were treated by a mobile team, and 14 by other doctors; the median response times were 11.5 (range 3-47) and 19 (range 5-60) min, respectively. All patients treated by pediatricians or mobile doctor teams received intravenous or intramuscular diazepam, whereas 50% of those treated by other doctors initially received diazepam suppositories. In three of the 20 events, establishing intravenous access was difficult. SIGNIFICANCE: In rural Japan, many children with seizures are initially treated by doctors other than pediatricians or emergency physicians, and they require a longer time to achieve seizure cessation. Non-intravenous benzodiazepine formulas, which have not yet been approved in Japan, would be helpful.

DOI： 10.1016/j.braindev.2020.08.004

Combination of tumor necrosis factor-α and epidermal growth factor induces the adrenergic-to-mesenchymal transdifferentiation in SH-SY5Y neuroblastoma cells. International journal Open Access

Yue Huang, Shoma Tsubota, Nobuhiro Nishio, Yoshiyuki Takahashi, Kenji Kadomatsu

Cancer science Vol. 112 ( 2 ) page： 715 - 724 2021.2

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

Neuroblastoma, a type of cancer that is common in children, is composed of two genetically clonal but epigenetically distinct cell types: mesenchymal (MES) and adrenergic (ADRN) types, controlled by super-enhancer-associated lineage-specific transcription factor networks. Mesenchymal-type cells are more migratory, resistant to chemotherapy, and prevalent in relapse tumors. Importantly, both cell types spontaneously transdifferentiate into one another, and this interconversion can be induced by genetic manipulations. However, the mechanisms of their spontaneous transdifferentiation and extracellular factors inducing this phenomenon have not yet been elucidated. Using a unique approach involving gene set enrichment analysis, we selected six ADRN and 10 MES candidate factors, possibly inducing ADRN and MES phenotypes, respectively. Treatment with a combination of 10 MES factors clearly induced the MES gene expression profile in ADRN-type SH-SY5Y neuroblastoma cells. Considering the effects on gene expression profile, migration ability, and chemoresistance, a combination of tumor necrosis factor alpha (TNF-α) and epidermal growth factor (EGF) was sufficient to synergistically induce the ADRN-to-MES transdifferentiation in SH-SY5Y cells. In addition, human neuroblastoma cohort analysis revealed that the expression of TNF and EGF receptors was strongly associated with MES gene expression signatures, supporting their important roles in transdifferentiation in vivo. Collectively, we propose a mechanism of neuroblastoma transdifferentiation induced by extracellular growth factors, which can be controlled in clinical situations, providing a new therapeutic possibility.

DOI： 10.1111/cas.14760

Shuffling babies and autism spectrum disorder. International journal

Yu Okai, Tomohiko Nakata, Kiyokuni Miura, Atsuko Ohno, Rie Wakako, Osamu Takahashi, Yuki Maki, Masaharu Tanaka, Yoko Sakaguchi, Yuji Ito, Hiroyuki Yamamoto, Hiroyuki Kidokoro, Yoshiyuki Takahashi, Jun Natsume

Brain & development Vol. 43 ( 2 ) page： 181 - 185 2021.2

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

BACKGROUND AND PURPOSE: Bottom shuffling is a locomotion strategy that precedes independent walking in some infants. Shuffling babies are generally considered to have favorable outcomes. The aim of the present study was to reveal clinical features and neurodevelopmental outcomes of shuffling babies who visited a child developmental center. METHODS: We studied 48 shuffling babies who visited Toyota Municipal Child Development Center from April 2007 to March 2015. We excluded patients with cerebral palsy, Down syndrome, or congenital disorders. In 2018, we retrospectively reviewed the clinical charts of the enrolled children. We investigated family history, neurological findings, and the developmental outcome during the follow-up period. RESULTS: During the follow-up period, 20 children (42%) were diagnosed with ASD. Gross motor development in infancy was not different between infants with and without ASD. The rate of poor eye contact at the first visit and a delay in the first word speech were significantly higher in infants with ASD than in infants without ASD. A family history of bottom shuffling was significantly less frequent in infants with ASD (10%) than in those without (39%). CONCLUSION: Some of bottom shufflers may represent ASD during follow-up. Paying attention to social and cognitive functions in shuffling babies is important.

DOI： 10.1016/j.braindev.2020.08.007

Long-term outcome in patients with Fanconi anemia who received hematopoietic stem cell transplantation: a retrospective nationwide analysis.

術前診断にて良性腫瘍と考えられたが全摘出できなかった腰髄腫瘍の2歳男児

吉田太郎, 村松秀城, 今屋雅之, 山森彩子, 若松学, 三輪田俊介, 成田幸太郎, 北澤宏展, 谷口理恵子, 市川大輔, 濱田太立, 西川英里, 川島希, 成田敦, 西尾信博, 小島勢二, 高橋義行, 田中智史, 安藤圭, 小林和克, 今釜史郎, 中黒匡人, 平戸純子

日本小児血液・がん学会雑誌 Vol. 57 ( 5 ) page： 409 - 410 2021.2

胎児発育不全に伴う脳発達異常の早期診断法確立に向けたバイオマーカーの探索

小野田淳人, 北瀬悠磨, 辻雅弘, 上田一仁, 高橋義行, 早川昌弘, 佐藤義朗

日本小児科学会雑誌 Vol. 125 ( 2 ) page： 216 - 216 2021.2

化学療法による治療介入を行った生後2ヵ月未満発症の神経芽腫4S

今屋雅之, 西川英里, 吉田太郎, 山森彩子, 若松学, 三輪田俊介, 成田幸太郎, 北澤宏展, 谷口理恵子, 市川大輔, 濱田太立, 川島希, 成田敦, 村松秀城, 西尾信博, 小島勢二, 高橋義行

日本小児血液・がん学会雑誌 Vol. 57 ( 5 ) page： 411 - 411 2021.2

Miharu Yabe, Tomohiro Morio, Ken Tabuchi, Daisuke Tomizawa, Daiichiro Hasegawa, Hiroyuki Ishida, Nao Yoshida, Takashi Koike, Yoshiyuki Takahashi, Katsuyoshi Koh, Yasuhiro Okamoto, Hideki Sano, Keisuke Kato, Yoshinobu Kanda, Hiroaki Goto, Junko Takita, Takako Miyamura, Maiko Noguchi, Koji Kato, Yoshiko Hashii, Yoshiko Astuta, Hiromasa Yabe

International journal of hematology Vol. 113 ( 1 ) page： 134 - 144 2021.1

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

We retrospectively analyzed nationwide records of 163 Fanconi anemia (FA) patients [aplastic anemia (AA), n = 118; myelodysplastic syndrome (MDS), n = 30; acute leukemia, n = 15] who underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 1987 and 2015 in Japan. An alternative donor was used in 119 (73%) patients, and 160 (98%) patients received a non-T-cell-depleted graft. With an 8.7-year median follow-up, 5-year overall survival (OS) was 81%. The 5-year OS was significantly higher in AA patients than in MDS and acute leukemia patients (89%, 71%, and 44%, respectively). In the MDS/leukemia group, factors associated with poor outcome in univariate analysis were older age at HSCT (≥ 18 years), conditioning regimen without anti-thymocyte or lymphocyte globulin, and grade II-IV acute graft-versus-host disease. After 1 year, of 137 survivors, 15 developed subsequent malignancies, of whom 12 were diagnosed with head and neck (HN)/esophageal cancer. An irradiation regimen and older age were associated with the risk of HN/esophageal cancer. Five of seven deaths were attributed to subsequent malignancies more than 5 years after HSCT. On the basis of the risk factors for HSCT in MDS/leukemia patients and subsequent malignancies, a more effective HSCT approach is required.

DOI： 10.1007/s12185-020-02991-x

A Breast-Fed Baby with Low KREC in TREC/KREC Newborn Screening Whose Mother Received Azathioprine Treatment

Detection of subclonal SETBP1 and JAK3 mutations in juvenile myelomonocytic leukemia using droplet digital PCR. Reviewed International journal

Manabu Wakamatsu, Yusuke Okuno, Norihiro Murakami, Shunsuke Miwata, Hironobu Kitazawa, Kotaro Narita, Shinsuke Kataoka, Daisuke Ichikawa, Motoharu Hamada, Rieko Taniguchi, Kyogo Suzuki, Nozomu Kawashima, Eri Nishikawa, Atsushi Narita, Nobuhiro Nishio, Seiji Kojima, Hideki Muramatsu, Yoshiyuki Takahashi

Leukemia Vol. 35 ( 1 ) page： 259 - 263 2021.1

Manabu Wakamatsu, Hideki Muramatsu, Daiei Kojima, Yusuke Okuno, Yoshimi Sakai, Yoko Nakajima, Tetsuya Ito, Nozomu Kawashima, Atsushi Narita, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Allogeneic Stem Cell Transplantation from Alternative Donors for Children with Aplastic Anemia

Atsushi Narita, Hideki Muramatsu, Masayuki Imaya, Ayako Yamamori, Taro Yoshida, Manabu Wakamatsu, Shunsuke Miwata, Koutaro Narita, Hironobu Kitazawa, Rieko Taniguchi, Motoharu Hamada, Daisuke Ichikawa, Eri Nishikawa, Nozomu Kawashima, Yusuke Okuno, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

BONE MARROW TRANSPLANTATION Vol. 55 ( SUPPL 1 ) page： 215 - 216 2020.12

Allogeneic Hematopoietic Cell Transplantation in First Remission in Children with AML: A Comparison of RIC and MAC

Asahito Hama, Daiki Yamashita, Daichi Sajiki, Hironobu Kitazawa, Hirotoshi Sakaguchi, Nao Yoshida, Nozomu Kawashima, Atsushi Narita, Hideki Muramatsu, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Clinical Features of Cord Colitis Syndrome in Children

Ryo Maemura, Atsushi Narita, Daisuke Ichikawa, Motoharu Hamada, Eri Nishikawa, Nozomu Kawashima, Nobuhiro Nishio, Hideki Muramatsu, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Biomarkers for Distinguishing between acute GVHD and HHV-6B-Associated Skin Rash after Hematopoietic Stem Cell Transplantation

Miura, H; Kudo, K; Tanaka, M; Takahashi, Y; Kojima, S; Yoshikawa, T

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

INFANTILE HEMISPHERIC BRAIN TUMOR WITH A GOPC-ROS1 FUSION GENE: A CASE REPORT Open Access

Rieko Taniguchi, Atsushi Natsume, Nozomu Kawashima, Shinji Tanioka, Hideki Muramatsu, Motoharu Hamada, Daisuke Ichikawa, Masayuki Imaya, Kotaro Narita, Michihiro Kurimoto, Yoshiki Shiba, Kosuke Aoki, Fumiharu Ohka, Junko Hirato, Toshihiko Wakabayashi, Yoshiyuki Takahashi

NEURO-ONCOLOGY Vol. 22 page： 377 - 377 2020.12

Development of Donor-Derived T cell EBV-LPD with Identical EBV Genome after Allogeneic CBT in the NK Cell-Type CAEBV Patient

Masayuki Imaya, Yusuke Okuno, Nozomu Kawashima, Manabu Wakamatsu, Hideki Muramatsu, Nobuhiro Nishio, Akihisa Sawada, Junichi Kawada, Yoshinori Ito, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Favorable Prognosis of Patients with Intermediate-Risk Neuroblastoma Having Residual Tumor after Treatment

Nobuhiro Nishio, Daisuke Ichikawa, Motoharu Hamada, Eri Nishikawa, Nozomu Kawashima, Atsushi Narita, Hideki Muramatsu, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Effect of Azacitidine in a Child with Fanconi Anemia and Myelodysplastic Syndrome Harboring Monosomy 7

Nozomu Kawashima, Masafumi Ito, Kotaro Narita, Daisuke Ichikawa, Eri Nishikawa, Atsushi Narita, Hideki Muramatsu, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome Open Access

Yasuyoshi Oka, Motoharu Hamada, Yuka Nakazawa, Hideki Muramatsu, Yusuke Okuno, Koichiro Higasa, Mayuko Shimada, Honoka Takeshima, Katsuhiro Hanada, Taichi Hirano, Toshiro Kawakita, Hirotoshi Sakaguchi, Takuya Ichimura, Shuichi Ozono, Kotaro Yuge, Yoriko Watanabe, Yuko Kotani, Mutsumi Yamane, Yumiko Kasugai, Miyako Tanaka, Takayoshi Suganami, Shinichiro Nakada, Norisato Mitsutake, Yuichiro Hara, Kohji Kato, Seiji Mizuno, Noriko Miyake, Yosuke Kawai, Katsushi Tokunaga, Masao Nagasaki, Seiji Kito, Keiichi Isoyama, Masafumi Onodera, Hideo Kaneko, Naomichi Matsumoto, Fumihiko Matsuda, Keitaro Matsuo, Yoshiyuki Takahashi, Tomoji Mashimo, Seiji Kojima, Tomoo Ogi

Science Advances Vol. 6 ( 51 ) page： eabd7197 - eabd7197 2020.12

Language：English Publishing type：Research paper (scientific journal) Publisher：American Association for the Advancement of Science (AAAS)

Rs671 in the aldehyde dehydrogenase 2 gene (<italic>ALDH2</italic>) is the cause of Asian alcohol flushing response after drinking. ALDH2 detoxifies endogenous aldehydes, which are the major source of DNA damage repaired by the Fanconi anemia pathway. Here, we show that the rs671 defective allele in combination with mutations in the alcohol dehydrogenase 5 gene, which encodes formaldehyde dehydrogenase (<italic>ADH5FDH</italic>), causes a previously unidentified disorder, AMeD (aplastic anemia, mental retardation, and dwarfism) syndrome. Cellular studies revealed that a decrease in the formaldehyde tolerance underlies a loss of differentiation and proliferation capacity of hematopoietic stem cells. Moreover, <italic>Adh5−/−Aldh2</italic>E506K/E506K double-deficient mice recapitulated key clinical features of AMeDS, showing short life span, dwarfism, and hematopoietic failure. Collectively, our results suggest that the combined deficiency of formaldehyde clearance mechanisms leads to the complex clinical features due to overload of formaldehyde-induced DNA damage, thereby saturation of DNA repair processes.

DOI： 10.1126/sciadv.abd7197

Hematopoietic Stem Cell Transplantation for Inborn Errors of Immunity in Japan: Overview of a Nationwide Retrospective Analysis

Miyamoto, S; Yanagimachi, M; Umeda, K; Iguchi, A; Sasahara, Y; Takada, H; Yamada, M; Ishimura, M; Koike, T; Yasui, M; Takahashi, Y; Kawaguchi, H; Kajiwara, M; Inoue, M; Kato, K; Hashii, Y; Atsuta, Y; Yabe, H; Imai, K; Morio, T

BONE MARROW TRANSPLANTATION Vol. 55 ( SUPPL 1 ) page： 102 - 103 2020.12

Hematopoietic Stem Cell Transplantation for Severe Combined Immunodeficiency in Japan: A Nationwide Retrospective Analysis

Miyamoto, S; Yanagimachi, M; Umeda, K; Iguchi, A; Sasahara, Y; Takada, H; Takahashi, Y; Kajiwara, M; Inoue, M; Kato, K; Hashii, Y; Atsuta, Y; Yabe, H; Imai, K; Morio, T

BONE MARROW TRANSPLANTATION Vol. 55 ( SUPPL 1 ) page： 443 - 443 2020.12

Viral Reactivations in Children with Aplastic Anemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Atsushi Narita, Yoshinori Ito, Nozomu Kawashima, Yusuke Okuno, Hideki Muramatsu, Nobuhiro Nishio, Yuka Torii, Junichi Kawada, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Microsatellite Instability-High is Rare Events in Refractory Pediatric Solid Tumors

Yoshida, T; Muramatsu, H; Wakamatsu, M; Taniguchi, R; Ichikawa, D; Nakaguro, M; Natsume, A; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Reduced Intensity Conditioning is Effective for Hematopoietic stem Cell Transplantation in Patients with Diamond-Blackfan ANEMIA

Koyamaishi, S; Kamio, T; Kobayashi, A; Sato, T; Kudo, K; Sasaki, S; Kanezaki, R; Hasegawa, D; Muramatsu, H; Takahashi, Y; Sasahara, Y; Hiramatsu, H; Kakuda, H; Tanaka, M; Ishimura, M; Nishi, M; Ishiguro, A; Yabe, H; Yoshida, K; Kanno, H; Ohga, S; Ohara, A; Kojima, S; Miyano, S; Ogawa, S; Toki, T; Terui, K; Ito, E

BONE MARROW TRANSPLANTATION Vol. 55 ( SUPPL 1 ) page： 36 - 37 2020.12

Strategy of Stem Cell Transplantation at 1st Molecular CR for Pediatric Acute Lymphoblastic Leukemia with MEF2D-BCL9 Fusion

Motoharu Hamada, Masayuki Imaya, Yusuke Okuno, Daisuke Ichikawa, Nozomu Kawashima, Atsushi Narita, Eri Nishikawa, Hideki Muramatsu, Nobuhiro Nishio, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Myelodysplastic syndromes in a pediatric patient with Cri du Chat syndrome with a ring chromosome 5. Reviewed

Akifumi Nozawa, Michio Ozeki, Shiho Yasue, Saori Endo, Tomonori Kadowaki, Hidenori Ohnishi, Hideki Muramatsu, Asahito Hama, Yoshiyuki Takahashi, Seiji Kojima, Toshiyuki Fukao

International journal of hematology Vol. 112 ( 5 ) page： 728 - 733 2020.11

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

Few hematological complications have previously been reported in association with Cri du Chat syndrome (CdCS). A case of myelodysplastic syndromes (MDS) in a pediatric patient with CdCS is herein presented. A 17-year-old female with CdCS caused by ring chromosome 5 was admitted to the hospital for investigation of a 1-month history of anemia. Based on the morphological findings of bone marrow, the patient was diagnosed with refractory cytopenia with multilineage dysplasia. The risk group was classified as intermediate-1 in the International Prognostic Scoring System (IPSS), and low in the revised IPSS. Assessment by microarray comparative genomic hybridization (CGH) identified the breakpoints of ring chromosome 5 as 46,XX,r(5)(p14.3q35.3). This revealed that the 5q terminal deletion did not include the common deleted region of MDS with del(5q). Treatment with azacitidine was initiated to control disease progression and improve quality of life. At baseline, the patient had a mean transfusion requirement of 3 units/month, which decreased to 2 units/month after six cycles of azacitidine and to 1 unit/month after 10 cycles of azacitidine. Cytopenia observed in the presented case seemed irrelevant to ring chromosome 5 which is the causative cytogenetic abnormality of CdCS, and further analyses may be needed to clarify the pathogenesis.

DOI： 10.1007/s12185-020-02909-7

Risk factors for secondary poor graft function after bone marrow transplantation in children with acquired aplastic anemia Reviewed International journal

Asahito Hama, Hideki Muramatsu, Atsushi Narita, Eri Nishikawa, Nozomu Kawashima, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

Pediatric transplantation Vol. 24 ( 7 ) page： e13828 2020.11

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

In patients with acquired AA, PGF is a major cause of cytopenia after hematopoietic stem cell transplantation. An increased incidence of PGF, especially sPGF, has been noted after the introduction of the FLU/CY regimen in children with acquired AA. To clarify the risk factors for sPGF, the clinical data of 49 patients (median age, 11 years; range, 1-19 years) with AA who received allogeneic BMT at Nagoya University Hospital from 1997 to 2016 were analyzed. Out of the 49 patients, 7 developed sPGF, and the 5-year CI was 0.15 (95% CI, 0.04-0.25). Five received the FLU/CY regimen, and the 5-year CI of sPGF was significantly higher in patients who received the regimen (0.36; 95% CI, 0.12-0.62) than in those who were conditioned with the non-FLU/CY regimen (0.06; 95% CI, 0.01-0.17; P =.01). The multivariate analysis confirmed that the FLU/CY regimen (hazard ratio, 6.12; 95% CI, 1.16-32.4; P =.03) was a significant risk factor for sPGF. sPGF improved spontaneously without stem cell boost infusions in 5 patients, ranging from 460 to 3539 days after BMT. The 10-year CI of the spontaneous trilineage recovery was 0.83 (95% CI, 0.00-0.97), and all 7 patients are alive. The FLU/CY regimen was identified as a risk factor for the sPGF development in patients with AA. The establishment of the optimal conditioning regimens for children with AA is warranted.

DOI： 10.1111/petr.13828

造血細胞移植後小児のキャッチアップ接種と移植細胞ソース別の比較検討

鈴木高子, 川田潤一, 西川英里, 山口慎, 奥村俊彦, 武内俊, 堀場千尋, 鳥居ゆか, 村松秀城, 高橋義行, 伊藤嘉規

日本小児感染症学会総会・学術集会プログラム・抄録集 Vol. 52回 page： 179 - 179 2020.11

分子医学・再生医療・心臓血管発生「先天性心疾患の理解・治療・予防につなげる臨床心臓発生学」 ABL1変異は先天性心疾患を伴う症候群の原因となるエクソーム解析と質量分析法を応用した遺伝性心室中隔欠損症の網羅的病態解明

山本英範, 早野聡, 奥野友介, 小野田淳人, 加藤耕治, 長井典子, 深澤佳絵, 齋藤伸治, 高橋義行, 加藤太一

日本小児循環器学会雑誌 Vol. 36 ( Suppl.2 ) page： s2 - 118 2020.11

Comprehensive pathogen detection in sera of Kawasaki disease patients by high-throughput sequencing: a retrospective exploratory study. International journal Open Access

Yuka Torii, Kazuhiro Horiba, Satoshi Hayano, Taichi Kato, Takako Suzuki, Jun-Ichi Kawada, Yoshiyuki Takahashi, Seiji Kojima, Yusuke Okuno, Tomoo Ogi, Yoshinori Ito

BMC pediatrics Vol. 20 ( 1 ) page： 482 - 482 2020.10

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

BACKGROUND: Kawasaki disease (KD) is an idiopathic systemic vasculitis that predominantly damages coronary arteries in children. Various pathogens have been investigated as triggers for KD, but no definitive causative pathogen has been determined. As KD is diagnosed by symptoms, several days are needed for diagnosis. Therefore, at the time of diagnosis of KD, the pathogen of the trigger may already be diminished. The aim of this study was to explore comprehensive pathogens in the sera at the acute stage of KD using high-throughput sequencing (HTS). METHODS: Sera of 12 patients at an extremely early stage of KD and 12 controls were investigated. DNA and RNA sequences were read separately using HTS. Sequence data were imported into the home-brew meta-genomic analysis pipeline, PATHDET, to identify the pathogen sequences. RESULTS: No RNA virus reads were detected in any KD case except for that of equine infectious anemia, which is known as a contaminant of commercial reverse transcriptase. Concerning DNA viruses, human herpesvirus 6B (HHV-6B, two cases) and Anelloviridae (eight cases) were detected among KD cases as well as controls. Multiple bacterial reads were obtained from KD and controls. Bacteria of the genera Acinetobacter, Pseudomonas, Delfita, Roseomonas, and Rhodocyclaceae appeared to be more common in KD sera than in the controls. CONCLUSION: No single pathogen was identified in serum samples of patients at the acute phase of KD. With multiple bacteria detected in the serum samples, it is difficult to exclude the possibility of contamination; however, it is possible that these bacteria might stimulate the immune system and induce KD.

DOI： 10.1186/s12887-020-02380-7

MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members.

Sas V, Pasca S, Jurj A, Pop L, Muramatsu H, Ono H, Dima D, Teodorescu P, Iluta S, Turcas C, Onaciu A, Munteanu R, Zimta AA, Blag C, Popa G, von Gamm EDA, Arghirescu S, Serban M, Man S, Marian M, Petrushev B, Berce C, Colita A, Zdrenghea M, Kojima S, Gulei D, Takahashi Y, Tomuleasa C

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology Vol. 54 ( 5 ) page： 994 - 1012 2020.10

Change of White Matter Integrity in Children With Hematopoietic Stem Cell Transplantation. International journal

Yoko Sakaguchi, Jun Natsume, Hiroyuki Kidokoro, Masaharu Tanaka, Yu Okai, Yuji Ito, Hiroyuki Yamamoto, Atsuko Ohno, Tomohiko Nakata, Toshiki Nakane, Hisashi Kawai, Toshiaki Taoka, Hideki Muramatsu, Shinji Naganawa, Yoshiyuki Takahashi

Pediatric neurology Vol. 111 page： 78 - 84 2020.10

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

BACKGROUND: Advances in hematopoietic stem cell transplantation have improved the survival rate of malignant diseases and congenital immunodeficiencies. It has become important to assess long-term complications in survivors. To assess neurological abnormalities in children treated by transplantation, diffusion tensor imaging was performed. METHODS: Forty children who underwent head diffusion tensor imaging before and after their first transplantation were enrolled. Patients with brain lesions on conventional MRI were excluded. Fractional anisotropy and mean diffusivity were compared between patients and 28 control subjects using tract-based spatial statistics. The Strengths and Difficulties Questionnaire was administered as a behavioral evaluation after transplantation, and diffusion tensor images of patients with and without behavioral abnormalities were compared. RESULTS: The age of patients and controls was 0 to 19 years and 0 to 16 years, respectively. The date of diffusion tensor imaging was 10 to 57 days before and 40 to 153 days after transplantation. Tract-based spatial statistics showed fractional anisotropy reduction in widespread white matter in patients before and after transplantation. Mean diffusivity was high before transplantation and normalized after transplantation. Analysis comparing before and after hematopoietic stem cell transplantation shows no difference in fractional anisotropy and a higher mean diffusivity before hematopoietic stem cell transplantation. In patients with behavioral abnormalities, low fractional anisotropy and high mean diffusivity remained after transplantation. CONCLUSIONS: Longitudinal diffusion tensor imaging showed white matter abnormalities in children without conventional MRI abnormalities, which were related to behavioral problems after transplantation. Diffusion tensor imaging is useful for behavioral assessment in children undergoing transplantation.

DOI： 10.1016/j.pediatrneurol.2020.06.008

Successful treatment with i.v. immunoglobulin and rituximab for bronchiolitis obliterans associated with paraneoplastic pemphigus. Reviewed International journal Open Access

Kaori Kaibuchi-Ando, Kazumitsu Sugiura, Yoshinao Muro, Yoshiyuki Takahashi, Seiji Kojima, Norito Ishii, Takashi Hashimoto, Masashi Akiyama

The Journal of dermatology Vol. 47 ( 10 ) page： E368 - E370 2020.10

臍帯血移植後、ドナー細胞に移植前と同一のEBV感染が確認された慢性活動性EBV感染症の再発例(Development of donor-derived T cell EBV-LPD with identical EBV genome after allogeneic CBT in the NK cell-type CAEBV patient)

Imaya Masayuki, Okuno Yusuke, Kawashima Nozomu, Wakamatsu Manabu, Muramatsu Hideki, Nishio Nobuhiro, Sawada Akihisa, Kawada Junichi, Ito Yoshinori, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 261 - 261 2020.10

治療後に腫瘍が残存している中間リスク神経芽腫患者の良好な予後(Favorable prognosis of patients with intermediate-risk neuroblastoma having residual tumor after treatment)

Nishio Nobuhiro, Ichikawa Daisuke, Hamada Motoharu, Nishikawa Eri, Kawashima Nozomu, Narita Atsushi, Muramatsu Hideki, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 251 - 251 2020.10

小児急性骨髄性白血病第一寛解期における同種造血細胞移植 RICとMACの比較(Allogeneic hematopoietic cell transplantation in first remission in children with AML: A comparison of RIC and MAC)

Hama Asahito, Yamashita Daiki, Sajiki Daichi, Kitazawa Hironobu, Sakaguchi Hirotoshi, Yoshida Nao, Kawashima Nozomu, Narita Atsushi, Muramatsu Hideki, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 221 - 221 2020.10

小児再生不良性貧血における同種造血細胞移植後のウイルス再活性化(Viral reactivations in children with aplastic anemia undergoing allogeneic hematopoietic stem cell transplantation)

Narita Atsushi, Ito Yoshinori, Kawashima Nozomu, Okuno Yusuke, Muramatsu Hideki, Nishio Nobuhiro, Torii Yuka, Kawada Junichi, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 235 - 235 2020.10

アザチオプリン内服中の母体から出生し、新生児マススクリーニングでKREC低値を認めた一例(A breast-fed baby with low KREC in TREC/KREC newborn screening whose mother received azathioprine treatment)

Wakamatsu Manabu, Muramatsu Hideki, Kojima Daiei, Okuno Yusuke, Sakai Yoshimi, Nakajima Yoko, Ito Tetsuya, Kawashima Nozomu, Narita Atsushi, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 241 - 241 2020.10

ファンコニ貧血を背景にモノソミー7を有する骨髄異形成症候群に対するアザシチジンの効果(Effect of azacitidine in a child with Fanconi anemia and myelodysplastic syndrome harboring monosomy 7)

Kawashima Nozomu, Ito Masafumi, Narita Kotaro, Ichikawa Daisuke, Nishikawa Eri, Narita Atsushi, Muramatsu Hideki, Nishio Nobuhiro, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 233 - 233 2020.10

小児におけるcord colitis syndromeの臨床的特徴(Clinical features of cord colitis syndrome in children)

Maemura Ryo, Narita Atsushi, Ichikawa Daisuke, Hamada Motoharu, Nishikawa Eri, Kawashima Nozomu, Nishio Nobuhiro, Muramatsu Hideki, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 261 - 261 2020.10

MEF2D-BCL9融合遺伝子陽性小児ALLに対する第一寛解期造血幹細胞移植(Strategy of stem cell transplantation at 1st molecular CR for pediatric acute lymphoblastic leukemia with MEF2D-BCL9 fusion)

Hamada Motoharu, Imaya Masayuki, Okuno Yusuke, Ichikawa Daisuke, Kawashima Nozomu, Narita Atsushi, Nishikawa Eri, Muramatsu Hideki, Nishio Nobuhiro, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 230 - 230 2020.10

Direct Delivery of piggyBac CD19 CAR T Cells Has Potent Anti-tumor Activity against ALL Cells in CNS in a Xenograft Mouse Model. Reviewed International journal Open Access

Kuniaki Tanaka, Itaru Kato, Miyuki Tanaka, Daisuke Morita, Kazuyuki Matsuda, Yoshiyuki Takahashi, Tatsutoshi Nakahata, Katsutsugu Umeda, Hidefumi Hiramatsu, Souichi Adachi, Junko Takita, Yozo Nakazawa

Molecular therapy oncolytics Vol. 18 page： 37 - 46 2020.9

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

The anti-CD19 chimeric antigen receptor (CAR) T cells showed excellent effect against acute lymphoblastic leukemia (ALL) in bone marrow (BM) in clinical trials. However, it remains to be elucidated whether the CD19 CAR T cell therapy is effective for ALL cells in central nervous system (CNS) because the patients with isolated or advanced CNS disease were excluded from clinical trials of systemic intravenous (i.v.) delivery of CAR T cells. Therefore, the preclinical evaluation for the efficacy of CAR T cell therapy against ALL cells in CNS is essential for clinical application. We evaluated the effect and adverse reaction of CD19 CAR T cells against ALL in CNS using a xenograft mouse model by i.v. or intra-cerebroventricular (i.c.v.) delivery of CAR T cells. Injection of piggyBac CD19 CAR T cells by i.v. had partial effects, whereas all CAR T i.c.v.-delivered mice had eliminated ALL in CNS. Although some CAR T i.c.v.-delivered mice showed transient changes of clinical symptoms during the first few days after treatment, none of CAR T i.c.v.-delivered mice displayed fatal adverse events. In this study, we demonstrated that direct delivery into CNS of CAR T cells is a possible therapeutic approach with the xenograft mouse model.

DOI： 10.1016/j.omto.2020.05.013

Association between graft source and response to live-attenuated vaccination in pediatric hematopoietic stem cell transplantation recipients: a single-center retrospective study. Reviewed International journal Open Access

Takako Suzuki, Jun-Ichi Kawada, Eri Nishikawa, Yuka Torii, Kazuhiro Horiba, Suguru Takeuchi, Toshihiko Okumura, Hideki Muramatsu, Yoshiyuki Takahashi, Yoshinori Ito

Bone marrow transplantation Vol. 55 ( 9 ) page： 1872 - 1874 2020.9

Establishment of a Novel Fetal Growth Restriction Model and Development of a Stem-Cell Therapy Using Umbilical Cord-Derived Mesenchymal Stromal Cells. International journal Open Access

Yuma Kitase, Yoshiaki Sato, Sakiko Arai, Atsuto Onoda, Kazuto Ueda, Shoji Go, Haruka Mimatsu, Mahboba Jabary, Toshihiko Suzuki, Miharu Ito, Akiko Saito, Akihiro Hirakawa, Takeo Mukai, Tokiko Nagamura-Inoue, Yoshiyuki Takahashi, Masahiro Tsuji, Masahiro Hayakawa

Frontiers in cellular neuroscience Vol. 14 page： 212 - 212 2020.7

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

Fetal growth restriction (FGR) is a major complication of prenatal ischemic/hypoxic exposure and affects 5%-10% of pregnancies. It causes various disorders, including neurodevelopmental disabilities due to chronic hypoxia, circulatory failure, and malnutrition via the placenta, and there is no established treatment. Therefore, the development of treatments is an urgent task. We aimed to develop a new FGR rat model with a gradual restrictive load of uterus/placental blood flow and to evaluate the treatment effect of the administration of umbilical cord-derived mesenchymal stromal cells (UC-MSCs). To create the FGR rat model, we used ameroid constrictors that had titanium on the outer wall and were composed of C-shaped casein with a notch and center hole inside that gradually narrowed upon absorbing water. The ameroid constrictors were attached to bilateral ovarian/uterine arteries on the 17th day of pregnancy to induce chronic mild ischemia, which led to FGR with over 20% bodyweight reduction. After the intravenous administration of 1 × 105 UC-MSCs, we confirmed a significant improvement in the UC-MSC group in a negative geotaxis test at 1 week after birth and a rotarod treadmill test at 5 months old. In the immunobiological evaluation, the total number of neurons counted via the stereological counting method was significantly higher in the UC-MSC group than in the vehicle-treated group. These results indicate that the UC-MSCs exerted a treatment effect for neurological impairment in the FGR rats.

DOI： 10.3389/fncel.2020.00212

Lower limb pain following allogeneic hematopoietic stem cell transplantation in Japanese children. Reviewed

Kenichi Mishima, Hiroshi Kitoh, Masaki Matsushita, Tadashi Nagata, Yasunari Kamiya, Yoshiyuki Takahashi, Naoki Ishiguro

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association Vol. 25 ( 4 ) page： 682 - 687 2020.7

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

BACKGROUND: Patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) can experience musculoskeletal pains in their lower limbs in the early and late post-transplantation period. This study investigated demographics and clinical characteristics of the lower limb pain (LLP) among Japanese survivors of pediatric allo-HSCT. METHODS: A total of 143 consecutive Japanese patients who had undergone allo-HSCT less than 18 years of age in a single institute between 2005 and 2015 were reviewed. Patients referred for in-house orthopedic evaluation of their sustained LLPs that impaired ambulation were defined as LLP group. Illness/transplantation-related parameters were compared between LLP group and non-LLP group. RESULTS: Ninety children with a mean age of 8.5 years at transplantation were enrolled. Their median follow-up period following transplantation was 6.3 years (range, 2.1-12.5). There were four patients in LLP group, whose etiologies were AVN of the femoral head and insufficiency fracture (ISF) of the tibia or the medial cuneiform bone. Cumulative dose of steroids that administered from six months before transplantation to six months after discharge from hospitalization for transplantation was significantly higher in LLP group than non-LLP group. Additionally, the two groups differed significantly in terms of hospitalization period after transplantation. LLP caused by AVN of the femoral head manifested between six months and two years, whereas that caused by ISF within the first six months after transplantation. CONCLUSIONS: The incidence of sustained LLP that impairs ambulation following contemporary allo-HSCT is not common in Japanese pediatric survivors. The risk of developing musculoskeletal LLP may increase with a higher steroid dosage in the peri-transplant period. LLP caused by AVN of the femoral head is likely to manifest later than that caused by ISF.

DOI： 10.1016/j.jos.2019.07.007

Conditioning regimen for allogeneic bone marrow transplantation in children with acquired bone marrow failure: fludarabine/melphalan vs. fludarabine/cyclophosphamide. Reviewed International journal

Nao Yoshida, Yoshiyuki Takahashi, Hiromasa Yabe, Ryoji Kobayashi, Kenichiro Watanabe, Kazuko Kudo, Miharu Yabe, Takako Miyamura, Katsuyoshi Koh, Hiroshi Kawaguchi, Hiroaki Goto, Naoto Fujita, Keiko Okada, Yasuhiro Okamoto, Koji Kato, Masami Inoue, Ritsuro Suzuki, Yoshiko Atsuta, Seiji Kojima

Bone marrow transplantation Vol. 55 ( 7 ) page： 1272 - 1281 2020.7

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

Fludarabine/cyclophosphamide-based conditioning regimens are standard in bone marrow transplantation (BMT) for acquired bone marrow failure in children, however, graft failure may occur. Using the data from a nationwide transplantation registry, we compared the outcomes of children aged <16 years with acquired aplastic anemia and refractory cytopenia of childhood who underwent allogeneic BMT with either fludarabine/melphalan (n = 71) or fludarabine/cyclophosphamide (n = 296) between 2000 and 2016. The fludarabine/melphalan regimen provided excellent outcomes, with 3-year overall survival and failure-free survival rates of 98% and 97%, respectively. The 83% 3-year failure-free survival in the fludarabine/cyclophosphamide group was significantly inferior (P = 0.002), whereas the overall survival did not differ between the two groups. Late graft failure was the most common cause of treatment failure in the fludarabine/cyclophosphamide group, which experienced a significantly higher incidence of late graft failure than the fludarabine/melphalan group (11% vs. 3%; P = 0.035). Multivariate analyses showed that the fludarabine/melphalan regimen was associated with a better failure-free survival (hazard ratio [HR] 0.12; P = 0.005) and lower risk of late graft failure (HR 0.16; P = 0.037). Fludarabine/melphalan-based conditioning regimen can be a promising option for children with acquired bone marrow failure receiving BMT.

DOI： 10.1038/s41409-020-0948-8

Targeting MEF2D-fusion Oncogenic Transcriptional Circuitries in B-cell Precursor Acute Lymphoblastic Leukemia

Tsuzuki, S; Yasuda, T; Kojima, S; Kawazu, M; Akahane, K; Inukai, T; Imaizumi, M; Morishita, T; Miyamura, K; Ueno, T; Karnan, S; Ota, A; Hyodo, T; Konishi, H; Sanada, M; Nagai, H; Horibe, K; Tomita, A; Suzuki, K; Muramatsu, H; Takahashi, Y; Miyazaki, Y; Matsumura, I; Kiyoi, H; Hosokawa, Y; Mano, H; Hayakawa, F

BLOOD CANCER DISCOVERY Vol. 1 ( 1 ) page： 82 - 95 2020.7

Targeting MEF2D-fusion Oncogenic Transcriptional Circuitries in B-cell Precursor Acute Lymphoblastic Leukemia Reviewed

Shinobu Tsuzuki, Takahiko Yasuda, Shinya Kojima, Masahito Kawazu, Koshi Akahane, Takeshi Inukai, Masue Imaizumi, Takanobu Morishita, Koichi Miyamura, Toshihide Ueno, Sivasundaram Karnan, Akinobu Ota, Toshinori Hyodo, Hiroyuki Konishi, Masashi Sanada, Hirokazu Nagai, Keizo Horibe, Akihiro Tomita, Kyogo Suzuki, Hideki Muramatsu, Yoshiyuki Takahashi, Yasushi Miyazaki, Itaru Matsumura, Hitoshi Kiyoi, Yoshitaka Hosokawa, Hiroyuki Mano, Fumihiko Hayakawa

Blood Cancer Discovery Vol. 1 ( 1 ) page： 82 - 95 2020.7

【骨髄不全症の病態と検査】骨髄不全症と遺伝子異常血球テロメア長測定の臨床的意義

成田敦, 高橋義行

臨床検査 Vol. 64 ( 7 ) page： 761 - 765 2020.7

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(株)医学書院

＜文献概要＞Point ●再生不良性貧血(AA)を含む骨髄不全症患者ではテロメア長の短縮がみられる.造血ストレスに伴う二次性の変化が原因と考えられている.●骨髄不全症患者の一部にはテロメラーゼ複合体遺伝子群の変異を有する患者がいる.診断補助としてテロメア長の測定が有用である.●特徴的な身体症状がみられない不全型の先天性角化不全症(DC)においてはテロメア長の測定や遺伝子診断が必須である.

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01541&link_issn=&doc_id=20200714070008&doc_link_id=10.11477%2Fmf.1542202408&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1542202408&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Safe diagnostic management of malignant mediastinal tumors in the presence of respiratory distress: a 10-year experience. Reviewed International journal Open Access

Tomoko Tanaka, Hizuru Amano, Yujiro Tanaka, Yoshiyuki Takahashi, Tatsuro Tajiri, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, Kazuki Yokota, Satoshi Makita, Yukiko Tani, Akinari Hinoki, Hiroo Uchida

BMC pediatrics Vol. 20 ( 1 ) page： 292 - 292 2020.6

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

BACKGROUND: The fundamental treatment for patients with pediatric malignant mediastinal tumors is chemotherapy. Therefore, accurate diagnosis is essential for selecting the appropriate chemotherapeutic regimen. However, malignant mediastinal tumors occasionally cause respiratory distress, and biopsies under general anesthesia are dangerous for such patients as invasive mechanical ventilation can aggravate airway obstruction caused by mass effect. In this study, we reviewed our 10-year diagnostic experience to evaluate the efficacy of our practices and confirm a safe diagnostic protocol for future patients. METHODS: We retrospectively reviewed medical records of children with malignant mediastinal tumors diagnosed at Nagoya University Hospital from 2007 to 2018 who demonstrated respiratory distress. Respiratory distress included dyspnea, massive pleural effusion, wheezing, and hypoxemia owing to tumors. Data on sex, age at onset, primary symptoms, location of tumor, management strategy (especially the method of diagnosis and definitive diagnosis), clinical course, prognosis during the acute phase (within 3 months from the onset of respiratory symptoms), and long-term outcome were collected. RESULTS: Twelve pediatric patients met the review criteria. There were seven anterior mediastinal tumors and five posterior mediastinal tumors. All anterior mediastinal tumors were diagnosed via bone marrow smear, thoracentesis, or core needle biopsy while maintaining spontaneous breathing. Regarding posterior tumors, two patients were diagnosed via a core needle biopsy and lymph node excisional biopsy under spontaneous breathing. Two cases were initially diagnosed solely using tumor markers. One patient with severe tracheal compression underwent tumor resection with extracorporeal membrane oxygenation stand-by. No patient died of diagnostic procedure-related complications. CONCLUSIONS: In 11 of the 12 cases reviewed, safe and accurate tumor diagnosis was accomplished without general anesthesia. A diagnostic strategy without general anesthesia considering the tumor location proved to be useful.

DOI： 10.1186/s12887-020-02183-w

Impact of graft-versus-host disease on the clinical outcome of allogeneic hematopoietic stem cell transplantation for non-malignant diseases. Reviewed

Katsutsugu Umeda, Kohsuke Imai, Masakatsu Yanagimachi, Hiromasa Yabe, Masao Kobayashi, Yoshiyuki Takahashi, Michiko Kajiwara, Nao Yoshida, Yuko Cho, Masami Inoue, Yoshiko Hashii, Yoshiko Atsuta, Tomohiro Morio

International journal of hematology Vol. 111 ( 6 ) page： 869 - 876 2020.6

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

The impact of acute and chronic graft-versus-host disease (GVHD) on clinical outcomes was retrospectively analyzed in 960 patients with non-malignant diseases (NMD) who underwent a first allogeneic hematopoietic stem cell transplantation (HSCT). Grade III-IV acute GVHD (but not grade I-II) was significantly associated with a lower rate of overall survival (OS), and higher non-relapse mortality (NRM) than that seen in patients without acute GVHD. Extensive (but not limited) GVHD was significantly associated with a lower OS rate and higher NRM than that seen in patients without chronic GVHD. Any grade of acute (but not chronic) GVHD was significantly associated with a lower incidence of relapse and a lower proportion of patients requiring a second HSCT or donor lymphocyte infusion for graft failure or mixed chimerism, but its impact on OS was almost negligible. Acute GVHD was significantly associated with lower OS rates in all disease groups, whereas chronic GVHD was significantly associated with lower OS rates in the primary immunodeficiency and histiocytosis groups. In conclusion, acute and chronic GVHD, even if mild, was associated with reduced OS in patients receiving HSCT for NMD and effective strategies should, therefore, be implemented to minimize GVHD.

DOI： 10.1007/s12185-020-02839-4

A familial case of alveolar capillary dysplasia with misalignment of the pulmonary veins: the clinicopathological features and unusual glomeruloid endothelial proliferation. Reviewed International journal Open Access

Akiko Kitano, Masato Nakaguro, Seiichi Tomotaki, Shintaro Hanaoka, Masahiko Kawai, Akiko Saito, Masahiro Hayakawa, Yoshiyuki Takahashi, Hidenori Kawasaki, Takahiro Yamada, Masahiko Ikeda, Tetsuo Onda, Kazutoshi Cho, Hironori Haga, Atsuko Nakazawa, Sachiko Minamiguchi

Diagnostic pathology Vol. 15 ( 1 ) page： 48 - 48 2020.5

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

BACKGROUND: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare disorder of pulmonary vascular abnormality with persistent pulmonary hypertension of the newborn. The symptom usually presents within hours after birth, leading to an early demise. Heterozygous de novo point mutations and genomic deletions of the FOXF1 (forkhead box F1) gene or its upstream enhancer have been identified in most patients with ACD/MPV. Most cases of ACD/MPV are sporadic; however, familial cases are also reported in 10% of patients. CASE PRESENTATION: We herein report a case of familial ACD/MPV that showed unusual glomeruloid proliferation of endothelial cells. In this family, three of the four siblings died within two to 3 days after birth because of persistent pulmonary hypertension and respiratory failure. Only the second child remains alive and healthy. An autopsy was performed for the third and fourth children, resulting in a diagnosis of ACD/MPV based on the characteristic features, including misalignment of smaller pulmonary veins and lymphangiectasis. In both of these children, glomeruloid endothelial proliferation of vessels was noted in the interlobular septa. The vessels were immunohistochemically positive for D2-40, CD31, Factor VIII, and ERG, suggestive of differentiation for both lymphatic and blood vessels. CONCLUSIONS: Unusual glomeruloid endothelial proliferation was observed in a familial ACD/MPV case. This histologic feature has not been described previously in ACD/MPV or any other pulmonary disease. Although the histogenesis of this histologic feature is unclear, this finding may suggest that ACD/MPV is a compound vascular and lymphovascular system disorder that exhibits various histologic features.

DOI： 10.1186/s13000-020-00972-6

Clinical Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Juvenile Myelomonocytic Leukemia: A Report from the Japan Society for Hematopoietic Cell Transplantation. Reviewed International journal Open Access

Nao Yoshida, Hirotoshi Sakaguchi, Miharu Yabe, Daiichiro Hasegawa, Asahito Hama, Daisuke Hasegawa, Motohiro Kato, Maiko Noguchi, Kiminori Terui, Yoshiyuki Takahashi, Yuko Cho, Maho Sato, Katsuyoshi Koh, Harumi Kakuda, Hiroyuki Shimada, Yoshiko Hashii, Atsushi Sato, Koji Kato, Yoshiko Atsuta, Kenichiro Watanabe

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Vol. 26 ( 5 ) page： 902 - 910 2020.5

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

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for juvenile myelomonocytic leukemia (JMML), but few large studies of HSCT for JMML exist. Using data from the Japan Society for Hematopoietic Cell Transplantation registry, we analyzed the outcomes of 129 children with JMML who underwent HSCT between 2000 and 2011. The 5-year overall survival (OS) rate and cumulative incidence of relapse were 64% and 34%, respectively. A regimen of busulfan/fludarabine/melphalan was the most commonly used (59 patients) and provided the best outcomes; the 5-year OS rate reached 73%, and the cumulative incidences of relapse and transplantation-related mortality were 26% and 9%, respectively. In contrast, the use of the irradiation-based myeloablative regimen was the most significant risk factor for OS (hazard ratio [HR], 2.92; P = .004) in the multivariate model. In addition, chronic graft-versus-host disease (GVHD) was strongly associated with lower relapse (HR, 0.37; P = .029) and favorable survival (HR, 0.22; P = .006). The current study has shown that a significant proportion of children with JMML can be cured with HSCT, especially those receiving the busulfan/fludarabine/melphalan regimen. Based on the lower relapse and better survival observed in patients with chronic GVHD, additional treatment strategies that focus on enhancing graft-versus-leukemia effects may further improve survival.

DOI： 10.1016/j.bbmt.2019.11.029

Autologous Stem Cell Transplantation for Children With Renal Tumors, and Adults With Wilms Tumor: Retrospective Analysis of the Japanese Transplant Registry Unified Management Program. Reviewed International journal

Ryoji Kobayashi, Masami Inoue, Yoshiyuki Takahashi, Atsushi Kikuta, Atsushi Ogawa, Yuhki Koga, Katsuyoshi Koh, Yoshiko Hashii, Junichi Hara, Koji Kato, Ken Tabuchi, Kimikazu Matsumoto

Journal of pediatric hematology/oncology Vol. 42 ( 4 ) page： 251 - 255 2020.5

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

BACKGROUND: Almost all pediatric patients with renal tumors are diagnosed with nephroblastoma (Wilms tumor), clear cell sarcoma, or malignant rhabdoid tumor. The choice of treatment is important for relapsed and refractory patients with nephroblastoma. Furthermore, clear cell sarcoma of the kidney (CCSK) and malignant rhabdoid tumor of the kidney (MRTK) have a poor prognosis compared with nephroblastoma. Thus, stem cell transplantation (SCT) is sometimes selected to treat these tumors. PATIENTS AND METHODS: The authors targeted a total of 84 patients with nephroblastoma, CCSK, and MRTK who underwent a first autologous SCT between 1992 and 2014, and were registered in the Japanese Transplant Registry Unified Management Program system. The authors retrospectively analyzed the SCT data for survival rate. RESULTS: Five-year overall survival rates for nephroblastoma, CCSK, and MRTK were 72.4%±6.3%, 46.8%±13.8%, and 36.4%±14.5%, respectively. The event-free survival rates at 5 years were 64.9%±6.7%, 35.7%±12.8%, and 27.3%±13.4%, respectively. The relapse rates at 5 years were 25.3%±11.4%, 46.2%±28.4%, and 60.0%±43.1%, respectively. CONCLUSION: Although the survival rate for nephroblastoma was relatively high, those of CCSK and MRTK were poor.

DOI： 10.1097/MPH.0000000000001779

ヒト-ヒト感染が疑われる肺Mycobacterium abscessus complex症の小児症例

稲垣孝行, 高橋弘泰, 山田清文, 八木哲也, 高橋義行, 村松秀城, 手塚宜行, 安立なぎさ, 豊留有香, 長田ゆかり

日本化学療法学会雑誌 Vol. 68 ( 3 ) page： 444 - 444 2020.5

droplet digital PCRを用いた若年性骨髄単球性白血病におけるサブクローナルなSETBP1とJAK3変異の検出

若松学, 村上典寛, 奥野友介, 北澤宏展, 山森彩子, 今屋雅之, 吉田太郎, 三輪田俊介, 成田幸太郎, 北澤展典, 濱田太立, 市川大輔, 谷口理恵子, 西川英里, 川島希, 成田敦, 西尾信博, 村松秀城, 小島勢二, 高橋義行

日本小児科学会雑誌 Vol. 124 ( 5 ) page： 881 - 881 2020.5

droplet digital PCRを用いた若年性骨髄単球性白血病におけるサブクローナルなSETBP1とJAK3変異の検出

日本小児科学会雑誌 Vol. 124 ( 5 ) page： 881 - 881 2020.5

Biallelic VPS35L pathogenic variants cause 3C/Ritscher-Schinzel-like syndrome through dysfunction of retriever complex. Reviewed International journal

Kohji Kato, Yasuyoshi Oka, Hideki Muramatsu, Filipp F Vasilev, Takanobu Otomo, Hisashi Oishi, Yoshihiko Kawano, Hiroyuki Kidokoro, Yuka Nakazawa, Tomoo Ogi, Yoshiyuki Takahashi, Shinji Saitoh

Journal of medical genetics Vol. 57 ( 4 ) page： 245 - 253 2020.4

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

BACKGROUND: 3C/Ritscher-Schinzel syndrome is characterised by congenital cranio-cerebello-cardiac dysplasia, where CCDC22 and WASHC5 are accepted as the causative genes. In combination with the retromer or retriever complex, these genes play a role in endosomal membrane protein recycling. We aimed to identify the gene abnormality responsible for the pathogenicity in siblings with a 3C/Ritscher-Schinzel-like syndrome, displaying cranio-cerebello-cardiac dysplasia, coloboma, microphthalmia, chondrodysplasia punctata and complicated skeletal malformation. METHODS: Exome sequencing was performed to identify pathogenic variants. Cellular biological analyses and generation of knockout mice were carried out to elucidate the gene function and pathophysiological significance of the identified variants. RESULTS: We identified compound heterozygous pathogenic variants (c.1097dup; p.Cys366Trpfs*28 and c.2755G>A; p.Ala919Thr) in the VPS35L gene, which encodes a core protein of the retriever complex. The identified missense variant lacked the ability to form the retriever complex, and the frameshift variant induced non-sense-mediated mRNA decay, thereby confirming biallelic loss of function of VPS35L. In addition, VPS35L knockout cells showed decreased autophagic function in nutrient-rich and starvation conditions, as well as following treatment with Torin 1. We also generated Vps35l-/- mice and demonstrated that they were embryonic lethal at an early stage, between E7.5 and E10.5. CONCLUSIONS: Our results suggest that biallelic loss-of-function variants in VPS35L underlies 3C/Ritscher-Schinzel-like syndrome. Furthermore, VPS35L is necessary for autophagic function and essential for early embryonic development. The data presented here provide a new insight into the critical role of the retriever complex in fetal development.

DOI： 10.1136/jmedgenet-2019-106213

Mesenchymal stem/stromal cells stably transduced with an inhibitor of CC chemokine ligand 2 ameliorate bronchopulmonary dysplasia and pulmonary hypertension. Reviewed International journal

Toshihiko Suzuki, Yoshiaki Sato, Hidenori Yamamoto, Taichi Kato, Yuma Kitase, Kazuto Ueda, Haruka Mimatsu, Yuichiro Sugiyama, Atsuto Onoda, Shigeki Saito, Yoshiyuki Takahashi, Takayuki Nakayama, Masahiro Hayakawa

Cytotherapy Vol. 22 ( 4 ) page： 180 - 192 2020.4

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

Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone.

DOI： 10.1016/j.jcyt.2020.01.009

Clinical Characteristics and Treatment Outcomes of Pediatric Patients with Non-Hodgkin Lymphoma in East Asia. Reviewed International journal Open Access

Jin Kyung Suh, Yi-Jin Gao, Jing-Yan Tang, Shiann-Tarng Jou, Dong-Tsamn Lin, Yoshiyuki Takahashi, Seiji Kojima, Ling Jin, Yonghong Zhang, Jong Jin Seo

Cancer research and treatment : official journal of Korean Cancer Association Vol. 52 ( 2 ) page： 359 - 368 2020.4

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

PURPOSE: The presentations and geographic incidence of pediatric non-Hodgkin lymphoma (NHL) differ from those of adults. This study delineated the characteristics and outcomes of pediatric NHL in East Asia. MATERIALS AND METHODS: Medical records of 749 pediatric patients with NHL treated at participating institutions in mainland China, Japan, Korea, and Taiwan from January 2008 to December 2013 were reviewed. Demographic and clinical features, survival outcomes, and putative prognostic factors were analyzed. RESULTS: Five hundred thirty patients (71%) were male. The most common pathologic subtypes were Burkitt lymphoma (BL) (36%). Six hundred seven patients (81%) had advanced diseases at diagnosis. The 5-year overall survival and event-free survival (EFS) rates were 89% and 84%. The 5-year EFS rates of BL, lymphoblastic lymphoma, and diffuse large B-cell lymphoma were 88%, 88%, and 89%, and those of anaplastic large cell lymphoma (ALCL) and peripheral T-cell lymphoma (PTCL) were 71% and 56% (p < 0.001). Central nervous system involvement, high lactate dehydrogenase level (> 250 IU/mL), and advanced disease at diagnosis (≥ stage III) were associated with poor outcomes (p < 0.05). ALCL and PTCL relapsed more frequently than other pathologic subtypes (p < 0.001). CONCLUSION: In East Asia, PTCL was more frequent than in Western countries, and bone marrow involvement did not affect treatment outcome. This international study should motivate future collaborative study on NHL in East Asia.

DOI： 10.4143/crt.2019.219

【小児血液・腫瘍疾患の最前線】診療のトピックス高リスク神経芽腫に対するGD2抗体療法

高橋義行

小児科診療 Vol. 83 ( 4 ) page： 455 - 458 2020.4

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(株)診断と治療社

●神経芽腫に対する免疫療法の標的分子として、ジシアロガングリオシドGD2抗原タンパクに対するモノクローナル抗体がGD2抗体である。●治療毒性(疼痛、アレルギー反応、血管漏出症候群など)があるものの管理は可能で、欧米ではすでに高リスク神経芽腫の標準治療薬として保険承認されている。●わが国では米国製剤、欧州製剤ともに治験が行われており、ドラッグラグ解消のため早期承認が望まれている。(著者抄録)

Novel compound heterozygous MCOLN1 mutations identified in a Japanese girl with severe developmental delay and thin corpus callosum. Reviewed International journal

Naoya Yamaguchi, Kyoko Ban, Atsushi Suzuki, Yuji Nakamura, Kohji Kato, Hideki Muramatsu, Yusuke Okuno, Ayako Hattori, Tadashi Kaname, Yoshiyuki Takahashi, Shinji Saitoh

Brain & development Vol. 42 ( 3 ) page： 298 - 301 2020.3

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

Mucolipidosis type IV (MLIV) is a rare lysosomal storage disorder causing severe psychomotor developmental delay and progressive visual impairment. MLIV is an autosomal recessive disease caused by mutations in MCOLN1, which encodes for mucolipin-1. Here, we report a case of a 4-year-old Japanese girl with severe intellectual disability and motor deficits. Brain magnetic resonance imaging showed signal abnormalities in the white matter and thinning of the corpus callosum. Whole-exome sequencing was performed on the proband and her parents, and novel compound heterozygous mutations at c.936_938del (p.Phe313del) and c.1503dupC (p.Ile502Hisfs*106) in MCOLN1 (NM_020533.2) were identified in the proband. Additional biochemical examinations revealed elevated serum gastrin level and iron deficiency anemia, leading to the diagnosis of MLIV. More reports of such pathogenic mutations are expected to broaden the understanding of the channel function of mucolipin-1 and genotype-phenotype correlations.

DOI： 10.1016/j.braindev.2019.12.003

Respiratory illness and acute flaccid myelitis in the Tokai district in 2018. Reviewed International journal

Akihisa Okumura, Shingo Numoto, Hideyuki Iwayama, Hirokazu Kurahashi, Jun Natsume, Shinji Saitoh, Tetsushi Yoshikawa, Toshiyuki Fukao, Masahiro Hirayama, Yoshiyuki Takahashi

Pediatrics international : official journal of the Japan Pediatric Society Vol. 62 ( 3 ) page： 337 - 340 2020.3

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

BACKGROUND: An outbreak of acute flaccid myelitis was chronologically correlated with an outbreak of severe respiratory illness in Japan in 2015. We hypothesized that increases in children hospitalized with severe respiratory illnesses might also be associated with increase in acute flaccid myelitis in autumn 2018. METHODS: We explored the temporal correlations between respiratory illness outbreaks and acute flaccid myelitis during autumn season between 2016 and 2018 using questionnaire surveys. One questionnaire explored the monthly numbers of children with acute flaccid myelitis, Guillain-Barré syndrome, and other acute flaccid paralyses. The other questionnaire explored the monthly numbers of children hospitalized with respiratory illnesses associated with wheezing. A correlation between the monthly numbers of children with acute flaccid myelitis and those with respiratory illness was analyzed using the Pearson correlation test. RESULTS: Although the number of patients hospitalized with respiratory illness did not correlate with the number of those admitted with myelitis, increases in children aged 7-12 and 13-19 years requiring intensive care unit admission correlated temporally with an outbreak of acute flaccid myelitis. CONCLUSIONS: An increase in intensive care unit admissions to treat respiratory disease occurred in association with a cluster of acute flaccid myelitis. An increase in the number of intensive care unit admissions due to respiratory illness may be a clue to expect the occurrence of acute flaccid myelitis.

DOI： 10.1111/ped.14128

繰り返す胸痛の経過中に突然発症した心室頻拍の1例

三輪剛士, 山本英範, 深澤佳絵, 六鹿雅登, 加藤太一, 高橋義行

日本小児科学会雑誌 Vol. 124 ( 3 ) page： 611 - 612 2020.3

早期よりエトレチナートを投与し効果がみられた道化師様魚鱗癬の1例

近藤真生, 浅田英之, 本部和也, 郷間環, 新井紗記子, 上田一仁, 三浦良介, 呉尚治, 兵藤玲奈, 鈴木俊彦, 伊藤美春, 齊藤明子, 村松友佳子, 佐藤義朗, 山本ひかる, 加藤有一, 杉山裕一郎, 高橋義行, 早川昌弘

日本小児科学会雑誌 Vol. 124 ( 3 ) page： 609 - 610 2020.3

急性弛緩性脊髄炎による左上肢麻痺に対して神経移行術を施行した1例

西尾洋介, 中田智彦, 白木杏奈, 鈴木健史, 川口将宏, 牧祐輝, 田中雅大, 坂口陽子, 成田敦, 山本啓之, 城所博之, 梶田光春, 平田仁, 高橋義行, 夏目淳

日本小児科学会雑誌 Vol. 124 ( 3 ) page： 604 - 604 2020.3

小児がん・白血病治療における最新医療次世代シークエンサーの臨床応用と遺伝子導入T細胞療法

高橋義行

日本小児科学会雑誌 Vol. 124 ( 3 ) page： 582 - 582 2020.3

TREC/KRECキットを用いた新生児マススクリーニング検査法の有用性

若松学, 村松秀城, 片岡伸介, 山森彩子, 今屋雅之, 吉田太郎, 三輪田俊介, 成田幸太郎, 北澤宏展, 濱田太立, 市川大輔, 谷口理恵子, 西川英里, 川島希, 成田敦, 奥野友介, 西尾信博, 中島葉子, 伊藤哲哉, 柘植郁哉, 中村富美子, 酒井好美, 小島勢二, 高橋義行

日本小児科学会雑誌 Vol. 124 ( 3 ) page： 605 - 605 2020.3

Multilineage-differentiating stress enduring cellsの新生児低酸素性虚血性脳症に対する治療効果の検討

鈴木俊彦, 佐藤義朗, 上田一仁, 北瀬悠磨, 呉尚治, 三浦良介, 浅田英之, 兵藤玲奈, 伊藤美春, 齊藤明子, 村松友佳子, 高橋義行, 早川昌弘

日本小児科学会雑誌 Vol. 124 ( 3 ) page： 595 - 596 2020.3

Human herpesvirus-6B infection in pediatric allogenic hematopoietic stem cell transplant patients: Risk factors and encephalitis. Reviewed International journal

Hiroki Miura, Yoshiki Kawamura, Fumihiko Hattori, Makito Tanaka, Kazuko Kudo, Masaru Ihira, Hiroshi Yatsuya, Yoshiyuki Takahashi, Seiji Kojima, Hirotoshi Sakaguchi, Nao Yoshida, Asahito Hama, Tetsushi Yoshikawa

Transplant infectious disease : an official journal of the Transplantation Society Vol. 22 ( 1 ) page： e13203 2020.2

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

BACKGROUND: Human herpesvirus-6B (HHV-6B) infection after allogenic hematopoietic stem cell transplantation (allo-HSCT) is known to be associated with post-transplant limbic encephalitis in adults. Meanwhile, the association between HHV-6B infection and central nervous system complications remains unclear in pediatric allo-HSCT patients. METHODS: In this study, HHV-6B infection was monitored for more than 50 days after HSCT using virus isolation and real-time PCR. Clinical information such as patient background and encephalitis status was collected retrospectively from medical records. Risk factors for HHV-6B infection were determined by the Cox proportional hazards model, and the clinical features of HHV-6B encephalitis in pediatric allo-HSCT patients were elucidated. RESULTS: Human herpesvirus-6B infection was observed in 74 (33.8%) of 219 patients at 3-47 days (median 18, interquartile range 13-20). Risk factors identified in multivariable analysis were hematological malignancy (hazards ratio [HR], 5.0; 95% confidence interval [CI], 2.3/12.5; P < .0001), solid tumor (HR, 4.8; CI, 1.5/16.3; P = .0104), unrelated donor (HR, 2.1; CI, 1.0/4.6; P = .0378), and sex-mismatched donor (HR 1.8; CI, 1.1/3.0; P = .0257). HHV-6B encephalitis occurred in only one of the 219 patients (0.46%); this patient demonstrated the typical clinical course of posterior reversible encephalopathy syndrome. CONCLUSION: Hematological malignancy, solid tumor, unrelated donor, and sex-mismatched donor were significant risk factors for HHV-6B infection after pediatric allo-HSCT. In pediatric allo-HSCT patients, the incidence of HHV-6B encephalitis was low and the clinical features differed from those in adult patients.

DOI： 10.1111/tid.13203

Pseudo-sawtooth pattern on amplitude-integrated electroencephalography in neonatal hypoxic-ischemic encephalopathy. International journal Open Access

Masaharu Tanaka, Hiroyuki Kidokoro, Tetsuo Kubota, Tatsuya Fukasawa, Yu Okai, Yoko Sakaguchi, Yuji Ito, Hiroyuki Yamamoto, Atsuko Ohno, Tomohiko Nakata, Tamiko Negoro, Akihisa Okumura, Toru Kato, Kazuyoshi Watanabe, Yoshiyuki Takahashi, Jun Natsume

Pediatric research Vol. 87 ( 3 ) page： 529 - 535 2020.2

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

OBJECTIVE: The objective of this study was to describe a novel amplitude-integrated electroencephalography (aEEG) pattern in infants with hypoxic-ischemic encephalopathy (HIE) and to assess the clinical significance. METHODS: The aEEG traces of infants with HIE who were treated with therapeutic hypothermia (TH) from 2012 to 2017 were analyzed. A pseudo-sawtooth (PST) pattern was defined as a periodic increase of the upper and/or lower margin of the trace on aEEG without showing seizure activities on conventional EEG (CEEG). RESULTS: Of the 46 infants, 6 (13%) had the PST pattern. The PST pattern appeared following a flat trace or a continuous low-voltage pattern and was followed by a burst-suppression pattern. On CEEG, the PST pattern consists of alternating cycles of low-voltage irregular activities and almost flat tracing. The PST pattern was associated with neuroimaging abnormalities and with various degrees of neurodevelopmental outcomes. Positive predictive values of the PST or worse pattern for adverse outcomes were high at 12 h after birth. CONCLUSION: A novel aEEG background pattern in infants with HIE was reported. The PST pattern likely indicates a suppressed background pattern and may be linked to unfavorable outcomes. Further multicenter validation study is needed to clarify its clinical significance.

DOI： 10.1038/s41390-019-0567-5

造血幹細胞移植を受けた小児における拡散テンソル画像解析

坂口陽子, 城所博之, 白木杏奈, 鈴木健史, 川口将宏, 牧祐輝, 田中雅大, 山本啓之, 中田智彦, 村松秀城, 高橋義行, 夏目淳

日本小児科学会雑誌 Vol. 124 ( 2 ) page： 290 - 290 2020.2

腫瘍性疾患と鑑別を要したPhlegmonous gastritisの小児例

三輪田俊介, 成田敦, 吉田太郎, 今屋雅之, 山森彩子, 若松学, 成田幸太郎, 北澤宏展, 濱田太立, 市川大輔, 谷口理恵子, 西川英里, 川島希, 奥野友介, 村松秀城, 西尾信博, 小島勢二, 阿部直紀, 岩田直美, 高橋義行

日本小児科学会雑誌 Vol. 124 ( 2 ) page： 333 - 333 2020.2

神経芽腫寛解導入療法における重症呼吸器症状のリスク因子の検討(Severe respiratory symptoms during induction chemotherapy in neuroblastoma)

松井基浩, 山岡祥子, 斎藤雄弥, 横川裕一, 牧本敦, 西川英里, 川島希, 成田敦, 西尾信博, 村松秀城, 高橋義行, 浦島充佳, 湯坐有希

日本小児科学会雑誌 Vol. 124 ( 2 ) page： 294 - 294 2020.2

川崎病症例における血清中微生物メタゲノム解析

鳥居ゆか, 堀場千尋, 早野聡, 加藤太一, 鈴木高子, 川田潤一, 高橋義行, 小島勢二, 伊藤嘉規

日本小児科学会雑誌 Vol. 124 ( 2 ) page： 223 - 223 2020.2

Targetable driver mutations in multicentric reticulohistiocytosis. Reviewed International journal Open Access

Norihiro Murakami, Tomohisa Sakai, Eisuke Arai, Hideki Muramatsu, Daisuke Ichikawa, Shuji Asai, Yoshie Shimoyama, Naoki Ishiguro, Yoshiyuki Takahashi, Yusuke Okuno, Yoshihiro Nishida

Haematologica Vol. 105 ( 2 ) page： E61 - E64 2020.1

A Novel Treatment with Stem Cells from Human Exfoliated Deciduous Teeth for Hypoxic-Ischemic Encephalopathy in Neonatal Rats. Reviewed International journal

Yuma Kitase, Yoshiaki Sato, Kazuto Ueda, Toshihiko Suzuki, Alkisti Mikrogeorgiou, Yuichiro Sugiyama, Kohki Matsubara, Yuka Tsukagoshi Okabe, Shinobu Shimizu, Hitoshi Hirata, Hiroshi Yukawa, Yoshinobu Baba, Masahiro Tsuji, Yoshiyuki Takahashi, Akihito Yamamoto, Masahiro Hayakawa

Stem cells and development Vol. 29 ( 2 ) page： 63 - 74 2020.1

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

Recently, cell therapy has been developed as a novel treatment for perinatal hypoxic-ischemic encephalopathy (HIE), which is an important cause of neurological disorder and death, and stem cells from human exfoliated deciduous teeth (SHED) express early markers for mesenchymal and neuroectodermal stem cells. We investigated the treatment effect of SHED for HIE in neonatal rats. Seven-day-old rats underwent ligation of the left carotid artery and were exposed to 8% hypoxic treatment. SHED (1 × 105 cells) were injected via the right external jugular vein 24 h after the insult. The effect of intravenous administration of SHED cells was evaluated neurologically and pathophysiologically. In the evaluation of engraftment using quantum dots 655, only a few SHED were detected in the injured cortex. In the immunohistological evaluation 24 h after injection, the numbers of positive cells of active caspase-3 and anti-4 hydroxynonenal antiserum were lower in the SHED group than in the vehicle group. The number of Iba-1+ cells in the cortex was higher in the SHED group. However, the proportion of M1 microglia (Iba-1+/ED-1+) was significantly decreased, whereas M2 microglia (Iba-1+/CD206+) tended to increase in the SHED group. In the behavioral tests performed 5 months after hypoxic treatment, compared to the vehicle group, the SHED group showed significant elongation of the endurance time in the rotarod treadmill test, significantly ameliorated proportion of using the impaired hand in the cylinder test, significantly lower ratio of right/left front paw area in gait analysis, and significantly higher avoidance rate in the active avoidance test. In the in vitro experiment with cultured neurons exposed to oxygen-glucose deprivation, we confirmed the neuroprotective effect of the condition medium of SHED. These results suggested that intravenous administration of SHED exerted a treatment effect both histologically and functionally, possibly via a paracrine effect.

DOI： 10.1089/scd.2019.0221

A Case of a 14-Year-Old Boy who had Difficulty Walking Due to Drug-Induced Neuropathy During T-Cell Acute Lymphocytic Leukemia Treatment

Taro Yoshida, Aya Sawamura, Hideki Muramatsu, Masayuki Imaya, Ayako Yamamori, Manabu Wakamatsu, Shunsuke Miwata, Kotaro Narita, Hironobu Kitazawa, Rieko Taniguchi, Daisuke Ichikawa, Eri Nishikawa, Motoharu Hamada, Nozomu Kawashima, Atsushi Narita, Nobuhiro Nishio, Seiji Kojima, Tomohiko Nakata, Hiroyuki Kidokoro, Jun Natxume, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S30 - S30 2019.12

A CaseWith Dyskeratosis Congenita Achieved Transfusion Independence after Eltrombopag Treatment

Wakamatsu, M; Muramatsu, H; Imaya, M; Yamamori, A; Yoshida, T; Miwata, S; Kitazawa, H; Narita, K; Ichikawa, D; Hamada, M; Taniguchi, R; Kawasima, N; Nishikawa, E; Narita, A; Okuno, Y; Nishio, N; Kojima, S; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 66 page： S46 - S46 2019.12

Clinical and Laboratory Characteristics of Atypical Chronic Myeloid Leukemia and Chronic Myelomonocytic Leukemia in Japanese Children

Hama, A; Ito, M; Hasegawa, D; Nozawa, K; Muramatsu, H; Takahashi, Y; Watanabe, K; Ohara, A; Manabe, A; Kojima, S

PEDIATRIC BLOOD & CANCER Vol. 66 page： S21 - S22 2019.12

An Infant With Hereditary Folate Malabsorption Requiring Differentiation from Acute Megakaryoblastic Leukemia

Eri Nishikawa, Rieko Taniguchi, Tarou Yoshida, Masayuki Imaya, Manabu Wakamatsu, Syunsuke Miwata, Koutarou Narita, Ayako Yamamori, Hironobu Kitazawa, Daisuke Ichikawa, Motoharu Hamada, Nozomu Kawashima, Atsushi Narita, Yusuke Okuno, Hideki Muramatsu, Nobuhiro Nishio, Seiji Kojima, Shimaa Said, Yusuke Tozawa, Masafumi Yamada, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S73 - S73 2019.12

Identification of FANCI Mutation in Fanconi Anemia in Infancy

Urata, T; Imamura, T; Osone, S; Muramatsu, H; Takahashi, Y; Hosoi, H

PEDIATRIC BLOOD & CANCER Vol. 66 page： S44 - S44 2019.12

Integrating FANCD2 Functional Analysis With High-Throughput Sequencing for Diagnosing Fanconi Anemia

Nozomu Kawashima, Yusuke Okuno, Hideki Muramatsu, Rieko Taniguchi, Taro Yoshida, Masayuki Imaya, Ayako Yamamori, Manabu Wakamatsu, Shunsuke Miwata, Kotaro Narita, Motoharu Hamada, Daisuke Ichikawa, Nobuhiro Kitazawa, Eri Nishikawa, Atsushi Narita, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S44 - S45 2019.12

Induction of Partial Response With Ceritinib for a Child With Chemotherapy-Refractory ALK-rearranged Neuroblastoma

Kotaro Narita, Taro Yoshida, Ayako Yamamori, Manabu Wakamatsu, Masayuki Imaya, Shunsuke Miwata, Hironobu Kitazawa, Rieko Taniguchi, Daisuke Ichikawa, Motoharu Hamada, Eri Nishikawa, Nobuhiro Nishio, Yusuke Okuno, Nozomu Kawashima, Atsushi Narita, Hideki Muramatsu, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S104 - S104 2019.12

Conditioning Regimen for Allogeneic Bone Marrow Transplantation in Children With Acquired Bone Marrow Failure: Fludarabine/Melphalan vs. Fludarabine/Cyclophosphamide

Yoshida, N; Takahashi, Y; Yabe, H; Kobayashi, R; Watanabe, K; Kudo, K; Yabe, M; Miyamura, T; Koh, K; Kawaguchi, H; Goto, H; Fujita, N; Hara, J; Okamoto, Y; Kato, K; Inoue, M; Suzuki, R; Atsuta, Y; Kojima, S

PEDIATRIC BLOOD & CANCER Vol. 66 page： S95 - S95 2019.12

Genetic Diagnosis Based on a Comprehensive Fusion Gene Analysis of Pediatric Malignant Solid Tumors

Daisuke Ichikawa, Hideki Muramatsu, Yusuke Okuno, Motoharu Hamada, Rieko Taniguchi, Eri Nishikawa, Nozomu Kawashima, Atsushi Narita, Nobuhiro Nishio, Yoshie Shimoyama, Masato Nakaguro, Shigeo Nakamura, Seiji Kojima, Atsuko Nakazawa, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S61 - S61 2019.12

Evaluation of the Outcome of KIR-Ligand Mismatched Cord Blood Transplantation for High Risk Metastatic Neuroblastoma Using New SIOPEN Risk Stratification

Nobuhiro Nishio, Daisuke Ichikawa, Manabu Wakamatsu, Kotaro Narita, Shunsuke Miwata, Hironobu Kitazawa, Rieko Taniguchi, Motoharu Hamada, Eri Nishikawa, Nozomu Kawashima, Yusuke Okuno, Atsushi Narita, Hideki Muramatsu, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S106 - S106 2019.12

Correlation Between Plasma Rabbit Anti-Thymocyte Globulin Level and Response to Immunosuppressive Therapy in Patients With Severe Aplastic Anemia

Atsushi Narita, Hideki Muramatsu, Motoharu Hamada, Daisuke Ichikawa, Eri Nishikawa, Nozomu Kawashima, Yusuke Okuno, Nobuhiro Nishio, Hirohito Yamazaki, Shinji Nakao, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S45 - S45 2019.12

Two Cases Effectively Treated with Oral Budesonide Administration for Steroid-resistant Intestinal Acute Graft Versus Host Disease

Ayako Yamamori, Eri Nishikawa, Atsushi Narita, Masayuki Imaya, Manabu Wakamatsu, Taro Yoshida, Shunsuke Miwata, Hironobu Kitazawa, Kotaro Narita, Rieko Taniguchi, Daisuke Ichikawa, Motoharu Hamada, Nozomu Kawashima, Yusuke Okuno, Nobuhiro Nishio, Hideki Muramatsu, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S37 - S38 2019.12

Whole Exome Sequencing Contributes to Genetic Diagnosis of IBMFS Patients

Hideki Muramatsu, Motoharu Hamada, Yusuke Okuno, Manabu Wakamatsu, Rieko Taniguchi, Koutarou Narita, Nozomu Kawashima, Hironobu Kitazawa, Daisuke Ichikawa, Eri Nishikawa, Nazomu Kawashima, Atsushi Narita, Nobuhiro Nishio, Seiji Kojima, Tomoo Ogi, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S63 - S64 2019.12

Prediction of postnatal clinical course in primary congenital dilated cardiomyopathy. Reviewed International journal

Hidenori Yamamoto, Yoshie Fukasawa, Naoki Ohashi, Takehiko Yokoyama, Kazutaka Suzuki, Takaya Ota, Kazushi Yasuda, Kentaro Omoya, Yoshiyuki Takahashi, Taichi Kato

Pediatrics international : official journal of the Japan Pediatric Society Vol. 61 ( 12 ) page： 1196 - 1201 2019.12

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

BACKGROUND: The aim of this study was to investigate the prediction of postnatal prognosis using fetal and perinatal data in patients with primary congenital dilated cardiomyopathy (PCDCM), and to estimate the incidence of this disease. METHODS: We examined correlations between fetal or perinatal data and postnatal clinical course in a multicenter retrospective study of eight patients with PCDCM. Incidence was calculated in a population-based study. RESULTS: All patients developed heart failure at a median of 8 days (range, 0-43 days), and six patients died or required extracorporeal artificial heart therapy at a median of 67 days (range, 0-92 days). The cardiothoracic area ratio from fetal echocardiography, the Apgar score, and the standard deviation of birth weight correlated significantly with the date at onset of heart failure. However, no data correlated with survival. Cumulative incidence of PCDCM was calculated as 1.21 per 100 000 total births (95% confidence interval, 0.37 to 2.06). CONCLUSIONS: Primary congenital dilated cardiomyopathy has a poor prognosis, but cardiothoracic area ratio from fetal echocardiography, body weight at birth, and Apgar score correlate with the timing of the onset of heart failure, and these indicators might therefore be useful for peri- and postnatal management.

DOI： 10.1111/ped.14029

Successful Treatment of Central Nervous System Relapses of Neuroblastoma Stage 4 After a KIR-ligand Mismatched Allogeneic Cord Blood Transplantation

Masayuki Imaya, Atsushi Narita, Taro Yoshida, Ayako Yamamori, Manabu Wakamatsu, Syunsuke Miwata, Kotaro Narita, Hironobu Kitazawa, Rieko Taniguchi, Daisuke Ichikawa, Motoharu Hamada, Eri Nishikawa, Nozomu Kawashima, Hideki Muramatsu, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S102 - S102 2019.12

Successfully Treated Three Children With Pericardial Effusion After Hematopoietic Stem Cell Transplantation

Hironobu Kitazawa, Atsushi Narita, Taro Yoshida, Masayuki Imaya, Ayako Yamamori, Manabu Wakamatsu, Shunsuke Miwata, Kotaro Narita, Rieko Taniguchi, Motoharu Hamada, Daisuke Ichikawa, Eri Nishikawa, Nozomu Kawashima, Yusuke Okuno, Nobuhiro Nishio, Hideki Muramatsu, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 66 page： S97 - S97 2019.12

Comprehensive Mutational Analysis of Juvenile Myelomonocytic Leukemia Using Whole-Genome Sequencing Open Access

Yusuke Okuno, Hideki Muramatsu, Norihiro Murakami, Nozomu Kawashima, Manabu Wakamatsu, Hironobu Kitazawa, Tomoo Ogi, Yoshiyuki Takahashi

BLOOD Vol. 134 2019.11

Genome-Wide Methylation Analysis Using the Digital Restriction Enzyme Analysis of Methylation for Stratification of Patients with Juvenile Myelomonocytic Leukemia Open Access

Hironobu Kitazawa, Hideki Muramatsu, Norihiro Murakami, Yusuke Okuno, Manabu Wakamatsu, Taro Yoshida, Masayuki Imaya, Ayako Yamamori, Shunsuke Miwata, Kotaro Narita, Motoharu Hamada, Daisuke Ichikawa, Rieko Taniguchi, Nozomu Kawashima, Eri Nishikawa, Atsushi Narita, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

BLOOD Vol. 134 2019.11

DNA Methylation As a Biomarker of Outcome in JMML: An International Effort Towards Clinical Implementation

Meyer, J; Schönung, M; Flotho, C; Olshen, AB; Hartmann, M; Plass, C; Okuno, Y; Takahashi, Y; Murakami, N; Wakamatsu, M; Loh, ML; Niemeyer, CM; Muramatsu, H; Lipka, DB; Stieglitz, E

BLOOD Vol. 134 2019.11

Detection of Subclonal SETBP1 and JAK3 Mutations in Patients with Juvenile Myelomonocytic Leukemia Using Droplet Digital PCR Open Access

Wakamatsu, M; Muramatsu, H; Murakami, N; Okuno, Y; Kitazawa, H; Kojima, S; Takahashi, Y

BLOOD Vol. 134 2019.11

High Natural Killer Cell Count at Diagnosis Predicts a Good Response to Immunosuppressive Therapy in Aplastic Anemia

Atsushi Narita, Hideki Muramatsu, Yinyan Xu, Motoharu Hamada, Daisuke Ichikawa, Eri Nishikawa, Nozomu Kawashima, Yusuke Okuno, Nobuhiro Nishio, Hirohito Yamazaki, Shinji Nakao, Seiji Kojima, Yoshiyuki Takahashi

BLOOD Vol. 134 2019.11

Utility of Newborn Screening for Severe Combined Immunodeficiency and X-Linked Agammaglobulinemia Using TREC and KREC Assays Open Access

Wakamatsu, M; Muramatsu, H; Kataoka, S; Okuno, Y; Yoshimi, S; Nakajima, Y; Ito, T; Tsuge, I; Kojima, S; Takahashi, Y

BLOOD Vol. 134 2019.11

Phase I Study of Cord Blood Transplantation with Intra-Bone Marrow Injection of Mesenchymal Stem Cells

Goto, T; Murata, M; Nishida, T; Terakura, S; Kamoshita, S; Ishikawa, Y; Ushijima, Y; Adachi, Y; Kato, K; Hirakawa, A; Nishiwaki, S; Nishio, N; Takahashi, Y; Kodera, Y; Matsushita, T; Kiyoi, H

BLOOD Vol. 134 2019.11

Corrigendum to "Frequent intragenic microdeletions of elastin in familial supravalvular aortic stenosis." [Int. J. Cardiol., 274 (2019) 290-295]. Reviewed International journal Open Access

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

International journal of cardiology Vol. 292 page： 283 - 283 2019.10

Prospective randomized trial comparing two doses of rabbit anti-thymocyte globulin in patients with severe aplastic anaemia. Reviewed International journal Open Access

Atsushi Narita, Xiaofan Zhu, Hideki Muramatsu, Xiaojuan Chen, Ye Guo, Wenyu Yang, Jingliao Zhang, Fang Liu, Jun H Jang, Hoon Kook, Hawk Kim, Kensuke Usuki, Hirohito Yamazaki, Yoshiyuki Takahashi, Shinji Nakao, Jong Wook Lee, Seiji Kojima

British journal of haematology Vol. 187 ( 2 ) page： 227 - 237 2019.10

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

The treatment of choice for patients with severe aplastic anaemia (SAA) includes immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG) and ciclosporin A. However, the optimal dose for rabbit ATG has yet to be established. We herein report the first prospective, randomized, multicentre study comparing two doses of rabbit ATG in patients with SAA. Patients with SAA who required initial IST in Japan (n = 89), China (n = 85) and Korea (n = 48) were enrolled between May 2012 and October 2017. A 1:1 block randomization was employed for two doses of rabbit ATG. In total, 222 patients were randomized, with 112 patients receiving 2·5 mg/kg and 110 receiving 3·5 mg/kg of rabbit ATG for 5 days. The primary endpoint was the haematological response at day 180. After 6 months, no significant difference in response rates was observed between the 2·5 and 3·5 mg/kg groups (49% vs. 48%, P = 0·894). Overall survival at 3 years was similar between the two groups [85% (95% confidence interval [CI], 76%-91%) vs. 91% (95% CI, 82%-96%); P = 0·107]. The current study revealed no significant differences in the efficacy and safety between the 2·5 and 3·5 mg/kg doses of rabbit ATG in patients with SAA. Trial registration: UMIN000011134.

DOI： 10.1111/bjh.16055

Retrospective analysis of children with high-risk acute myeloid leukemia who underwent allogeneic hematopoietic stem cell transplantation following complete remission with initial induction chemotherapy in the AML-05 clinical trial. Reviewed International journal

Nobuyuki Hyakuna, Yoshiko Hashii, Hiroyuki Ishida, Katsutsugu Umeda, Yoshiyuki Takahashi, Masayuki Nagasawa, Hiromasa Yabe, Yozo Nakazawa, Katsuyoshi Koh, Hiroaki Goto, Hiroyuki Fujisaki, Kimikazu Matsumoto, Harumi Kakuda, Michihiro Yano, Akio Tawa, Daisuke Tomizawa, Takashi Taga, Souichi Adachi, Koji Kato

Pediatric blood & cancer Vol. 66 ( 10 ) page： e27875 2019.10

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

In the AML-05 clinical trial conducted by the Japanese Pediatric Leukemia/Lymphoma Group from 2006 to 2010, children with high-risk acute myeloid leukemia (HR AML) received allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1). The aim of this study was to investigate the impact of allo-HSCT on the outcome of HR AML. Patients with either monosomy 7, 5q-, t(16;21), Ph1, FLT3-ITD, or induction failure after the first course of chemotherapy were eligible for transplant. Of 53 children with HR AML, 51 received allo-HSCT-45 in CR1, five in CR2, and one with non-CR. t(8;21), t(9;11), and t(16;21) abnormalities were identified in eight, five, and four patients, respectively. The stem cell sources varied-bone marrow in 30 patients, peripheral blood in three, and cord blood in 18. The median follow-up was 62 months. The overall survival (OS) rates at 3 years were 73% and 25% for patients who received transplant at CR1 and ≥CR2, respectively. Multivariable analysis showed that patients with chronic graft-versus-host disease (cGVHD) had better OS. This study supports that allo-HSCT is a suitable treatment for HR AML in CR1. The favorable outcome associated with cGVHD indicates that a graft-versus-leukemia effect might be occurring.

DOI： 10.1002/pbc.27875

重症複合型免疫不全患児から排泄されたRV1ワクチン株の院内伝播

三浦浩樹, 河村吉紀, 小澤慶, 成田幸太郎, 村松秀城, 高橋義行, 安岡竜平, 井平勝, 吉川哲史

日本小児感染症学会総会・学術集会プログラム・抄録集 Vol. 51回 page： 195 - 195 2019.10

造血幹細胞移植後に心嚢液貯留をきたした3例(Successfully treated three children with pericardial effusion after hematopoietic stem cell transplantation)

Kitazawa Hironobu, Narita Atsushi, Yoshida Taro, Imaya Masayuki, Yamamori Ayako, Wakamatsu Manabu, Miwata Shunsuke, Narita Kotaro, Taniguchi Rieko, Hamada Motoharu, Ichikawa Daisuke, Nishikawa Eri, Kawashima Nozomu, Okuno Yusuke, Nishio Nobuhiro, Muramatsu Hideki, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 258 - 258 2019.10

遺伝性造血不全症候群に対する全エクソーム解析(Whole exome sequencing contributes to genetic diagnosis of IBMFS patients)

Muramatsu Hideki, Hamada Motoharu, Okuno Yusuke, Wakamatsu Manabu, Taniguchi Rieko, Narita Kotaro, Miwata Shunsuke, Kitazawa Hironobu, Ichikawa Daisuke, Nishikawa Eri, Kawashima Nozomu, Narita Atsushi, Nishio Nobuhiro, Kojima Seiji, Ogi Tomoo, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 229 - 229 2019.10

最期の時間を在宅で過ごすことを選んだ高校生の一例予後告知前後の発言に焦点を当てて

佐々木美和, 滝良梨子, 牧田夏美, 萩原沙織, 清水直子, 梶山早苗, 谷口理恵子, 村松秀城, 高橋義行

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 375 - 375 2019.10

日本のAYA世代のがん対策の方向性を読み解く

栗本景介, 堀部敬三, 園原史訓, 猪川祥邦, 高見秀樹, 林真路, 神田光郎, 小林大介, 田中千恵, 山田豪, 中山吾郎, 小池聖彦, 清水千佳子, 高橋義行, 小寺泰弘

日本癌治療学会学術集会抄録集 Vol. 57回 page： P166 - 5 2019.10

急性リンパ性白血病治療中に薬剤性神経障害により歩行困難となった14歳男児例(A case of a 14-year-old boy who had difficulty walking due to drug-induced neuropathy during T-cell acute lymphocytic leukemia treatment)

Yoshida Taro, Sawamura Aya, Muramatsu Hideki, Imaya Masayuki, Yamamori Ayako, Wakamatsu Manabu, Miwata Shunsuke, Narita Kotaro, Kitazawa Hironobu, Taniguchi Rieko, Ichikawa Daisuke, Nishikawa Eri, Hamada Motoharu, Kawashima Nozomu, Narita Atsushi, Nishio Nobuhiro, Kojima Seiji, Nakata Tomohiko, Kidokoro Hiroyuki, Natxume Jun, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 200 - 200 2019.10

小児発熱性好中球減少症における次世代シークエンス病原微生物診断

堀場千尋, 鳥居ゆか, 原雄一郎, 嶋田繭子, 鈴木高子, 武内俊, 奥村俊彦, 川田潤一, 村松秀城, 高橋義行, 荻朋男, 伊藤嘉規

日本小児感染症学会総会・学術集会プログラム・抄録集 Vol. 51回 page： 196 - 196 2019.10

小児悪性固形腫瘍における網羅的な融合遺伝子検出に基づいた遺伝子診断(Genetic diagnosis based on a comprehensive fusion gene analysis of pediatric malignant solid tumors)

Ichikawa Daisuke, Muramatsu Hideki, Okuno Yusuke, Hamada Motoharu, Taniguchi Rieko, Nishikawa Eri, Kawashima Nozomu, Narita Atsushi, Nishio Nobuhiro, Shimoyama Yoshie, Nakaguro Masato, Nakamura Shigeo, Kojima Seiji, Nakazawa Atsuko, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 227 - 227 2019.10

小児がん拠点病院におけるQuality Indicator

藤崎弘之, 小松裕美, 井口晶裕, 笹原洋二, 康勝好, 湯坐有希, 後藤裕明, 高橋義行, 平山雅浩, 滝田順子, 家原知子, 井上雅美, 小阪嘉之, 川口浩史, 田口智章, 木下義晶, 米田光宏, 瀧本哲也, 松本公一

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 343 - 343 2019.10

がん免疫療法のUp to Date PiggyBacトランスポゾン法によるがんに対する遺伝子改変T細胞療法コスト削減の試み

高橋義行

日本癌治療学会学術集会抄録集 Vol. 57回 page： SSY3 - 3 2019.10

ステロイド抵抗性腸管急性移植片対宿主病に対して経口ブデゾニド投与が有効であった2例(Two cases effectively treated with oral budesonide administration for steroid-resistant intestinal acute graft versus host disease)

Yamamori Ayako, Nishikawa Eri, Narita Atsushi, Imaya Masayuki, Wakamatsu Manabu, Yoshida Taro, Miwata Shunsuke, Kitazawa Hironobu, Narita Kotaro, Taniguchi Rieko, Ichikawa Daisuke, Hamada Motoharu, Kawashima Nozomu, Okuno Yusuke, Nishio Nobuhiro, Muramatsu Hideki, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 207 - 207 2019.10

セリチニブにより部分奏効が得られたALK転座陽性の治療抵抗性神経芽腫の1例(Induction of partial response with ceritinib for a child with chemotherapy-refractory ALK-rearranged neuroblastoma)

Narita Kotaro, Yoshida Taro, Yamamori Ayako, Wakamatsu Manabu, Imaya Masayuki, Miwata Shunsuke, Kitazawa Hironobu, Taniguchi Rieko, Ichikawa Daisuke, Hamada Motoharu, Nishikawa Eri, Nishio Nobuhiro, Okuno Yusuke, Kawashima Nozomu, Narita Atsushi, Muramatsu Hideki, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 264 - 264 2019.10

ファンコニ貧血診断における次世代シークエンス解析とFANCD2機能解析の統合の意義(Integrating FANCD2 functional analysis with high-throughput sequencing for diagnosing Fanconi anemia)

Kawashima Nozomu, Okuno Yusuke, Muramatsu Hideki, Taniguchi Rieko, Yoshida Taro, Imaya Masayuki, Yamamori Ayako, Wakamatsu Manabu, Miwata Shunsuke, Narita Kotaro, Hamada Motoharu, Ichikawa Daisuke, Kitazawa Hironobu, Nishikawa Eri, Narita Atsushi, Nishio Nobuhiro, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 213 - 213 2019.10

ホジキンリンパ腫治療後に治療関連急性前骨髄性白血病を発症しATRA+ATO療法で治療した1例

山森彩子, 成田敦, 片岡伸介, 濱田太立, 市川大輔, 川島希, 西川英里, 西尾信博, 村松秀城, 小島勢二, 高橋義行

臨床血液 Vol. 60 ( 10 ) page： 1471 - 1471 2019.10

再生不良性貧血における血漿中ウサギATG血中濃度と免疫抑制療法反応率の関連性(Correlation between plasma rabbit anti-thymocyte globulin level and response to immunosuppressive therapy in patients with severe aplastic anemia)

Narita Atsushi, Muramatsu Hideki, Hamada Motoharu, Ichikawa Daisuke, Nishikawa Eri, Kawashima Nozomu, Okuno Yusuke, Nishio Nobuhiro, Yamazaki Hirohito, Nakao Shinji, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 213 - 213 2019.10

初診時急性巨核芽球性白血病と鑑別を要した遺伝性葉酸吸収障害の乳児例(An infant with hereditary folate malabsorption requiring differentiation from acute megakaryoblastic leukemia)

Nishikawa Eri, Taniguchi Rieko, Yoshida Taro, Imaya Masayuki, Wakamatsu Manabu, Miwata Shunsuke, Narita Kotaro, Yamamori Ayako, Kitazawa Hironobu, Ichikawa Daisuke, Hamada Motoharu, Kawashima Nozomu, Narita Atsushi, Okuno Yusuke, Muramatsu Hideki, Nishio Nobuhiro, Kojima Seiji, Said Shimaa, Tozawa Yusuke, Yamada Masafumi, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 238 - 238 2019.10

SIPOENスコアリングシステムを用いた、転移性高リスク神経芽腫に対するKIRリガンド不一致臍帯血移植の評価(Evaluation of the outcome of KIR-ligand mismatched cord blood transplantation for high risk metastatic neuroblastoma using new SIOPEN risk stratification)

Nishio Nobuhiro, Ichikawa Daisuke, Wakamatsu Manabu, Narita Kotaro, Miwata Shunsuke, Kitazawa Hironobu, Taniguchi Rieko, Hamada Motoharu, Nishikawa Eri, Kawashima Nozomu, Okuno Yusuke, Narita Atsushi, Muramatsu Hideki, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 266 - 266 2019.10

KIRリガンド不一致臍帯血移植後神経芽腫中枢神経再発に対し、摘出及び全脳全脊髄照射により無増悪生存中の2例(Successful treatment of central nervous system relapses of neuroblastoma stage 4 after a KIR-ligand mismatched allogeneic cord blood transplantation)

Imaya Masayuki, Narita Atsushi, Yoshida Taro, Yamamori Ayako, Wakamatsu Manabu, Miwata Syunsuke, Narita Kotaro, Kitazawa Hironobu, Taniguchi Rieko, Ichikawa Daisuke, Hamada Motoharu, Nishikawa Eri, Kawashima Nozomu, Muramatsu Hideki, Nishio Nobuhiro, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 263 - 263 2019.10

CAR-T細胞療法の基礎と臨床急性リンパ性白血病に対する非ウイルスベクター法を用いたCD19標的CAR-T細胞療法の開発

高橋義行

日本小児血液・がん学会雑誌 Vol. 56 ( 4 ) page： 165 - 165 2019.10

Delayed recognition of childhood arterial ischemic stroke. Reviewed International journal

Ikumi Hori, Takeshi Tsuji, Misa Miyake, Kazuto Ueda, Erina Kataoka, Michio Suzuki, Satoru Kobayashi, Hirokazu Kurahashi, Yoshiyuki Takahashi, Akihisa Okumura, Tetsushi Yoshikawa, Shinji Saitoh, Jun Natsume

Pediatrics international : official journal of the Japan Pediatric Society Vol. 61 ( 9 ) page： 895 - 903 2019.9

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

BACKGROUND: Few population-based surveys of childhood arterial ischemic stroke (AIS) have been conducted in Asian countries. The aim of this study was to investigate the clinical features, time to diagnosis, and prognosis of childhood AIS in a population-based cohort in Japan. METHODS: Children aged 29 days-15 years 11 months old, residing in the Aichi Prefecture of Japan with radiologically confirmed AIS during 2010-2014, were identified retrospectively through questionnaires. We analyzed 40 children (23 boys, 17 girls; median age, 7 years 3 months), and collected time interval information of 26 patients. The time from clinical onset to first physician assessment and the time to AIS diagnosis were calculated. RESULTS: The most common presentation was paralysis or paresis in 27 patients (71%). No underlying disorders or possible trigger factors were identified in 14 patients (35%). The median time from symptom onset to first physician assessment was 2.9 h. The median time from symptom onset to the confirmed AIS diagnosis was 27.0 h. The diagnosis of AIS was made in the first 6 h after onset of symptoms in 27% of patients for whom the time was available. Radiological diagnosis took longer than 24 h in 54% of these patients. CONCLUSIONS: Long in-hospital delays exist in the diagnosis of AIS in children, likely due to lack of awareness of stroke by doctors. Further efforts to increase public and physician awareness of childhood stroke are needed to ensure early diagnosis and treatment.

DOI： 10.1111/ped.13966

Risk factors for absence of catch-up growth in small for gestational age very low-birthweight infants. Reviewed International journal

Sakiko Arai, Yoshiaki Sato, Hideki Muramatsu, Hidenori Yamamoto, Fumiko Aoki, Yu Okai, Shinsuke Kataoka, Yu Hanada, Motoharu Hamada, Yoshihito Morimoto, Seiji Kojima, Jun Natsume, Yoshiyuki Takahashi

Pediatrics international : official journal of the Japan Pediatric Society Vol. 61 ( 9 ) page： 889 - 894 2019.9

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

BACKGROUND: Many small for gestational age (SGA) infants have catch-up growth during the first 2 years of life, but approximately 10% have no catch-up growth, and short stature continues into adulthood. Identification of risk factors for absence of catch-up growth at an early age may be useful for earlier diagnosis and earlier treatment. METHODS: This was a retrospective multicenter study. The subjects were SGA infants with very low-birthweight (VLBW), who were followed up until the age of 3 years. The risk factors for absence of catch-up growth were identified on statistical analysis. RESULTS: Of the 217 SGA infants in this study, 181 were in the catch-up group and 36 were in the no catch-up group. The catch-up rate was 83%. On multivariate analysis adjusted for gestational age, birthweight, birth height, and birth head circumference, multipara, Z and ΔZ scores of length at 12 months of corrected age, and the Z score of height at 24 months of corrected age were risk factors for lack of catch-up at 3 years. CONCLUSIONS: The length Z and ΔZ scores at 12 months of corrected age may be useful for an earlier diagnosis and earlier initiation of growth hormone treatment in VLBW infants.

DOI： 10.1111/ped.13939

SMARCA4不活化により発症し治療抵抗性を示した胸部腫瘍の1例

再発難治急性リンパ性白血病に対する新規治療戦略次世代シークエンサーの臨床応用と遺伝子導入T細胞療法

高橋義行

日本小児血液・がん学会雑誌 Vol. 56 ( 2 ) page： 244 - 244 2019.9

がんゲノム解析の新しい流れ(全ゲノム解析、クラウド解析、全がん解析、ロングリード解析などの新規技術) 若年性骨髄単球性白血病における全ゲノム解析(Frontiers in cancer genomics Whole-genome mutational analysis of juvenile myelomonocytic leukemia)

奥野友介, 村松秀城, 村上典寛, 川島希, 若松学, 北澤宏展, 荻朋男, 高橋義行

日本癌学会総会記事 Vol. 78回 page： S23 - 2 2019.9

市川大輔, 村松秀城, 奥野友介, 若松学, 三輪田俊介, 成田幸太郎, 北澤宏展, 濱田太立, 片岡伸介, 村上典寛, 谷口理恵子, 鈴木喬悟, 西川英里, 西尾信博, 川島希, 成田敦, 小島勢二, 高橋義行, 中黒匡人, 中村栄男, 中澤温子

日本小児血液・がん学会雑誌 Vol. 56 ( 2 ) page： 246 - 246 2019.9

CAR-T細胞の臨床応用急性リンパ性白血病に対する非ウイルスベクター法を用いたCAR-T細胞療法の開発(CAR-T in Clinics Development of CAR-T cell therapy for acute lymphoblastic leukemia using non-virus vector system)

高橋義行

日本癌学会総会記事 Vol. 78回 page： S5 - 2 2019.9

Constitutive activation of mTORC1 signaling induced by biallelic loss-of-function mutations in SZT2 underlies a discernible neurodevelopmental disease. Reviewed International journal Open Access

Yuji Nakamura, Kohji Kato, Naomi Tsuchida, Naomichi Matsumoto, Yoshiyuki Takahashi, Shinji Saitoh

PloS one Vol. 14 ( 8 ) page： e0221482 2019.8

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

There have been increasing number of reports of SZT2-related neurological diseases, the main symptoms of which are epilepsy, developmental delay, macrocephaly and a dysmorphic corpus callosum. SZT2 functions as a regulator of mechanistic target of rapamycin complex 1 (mTORC1) signaling in cultured human cell lines and mouse tissues. However, it remains to be determined whether mutations in SZT2 in human patients alter mTORC1 signaling. In this study, we aimed to investigate the functional consequence of biallelic SZT2 variants in Epstein-Barr virus-induced lymphoblastoid cell lines (LCLs) established from two patients with a typical SZT2-related neurodevelopmental disease. Increased phosphorylation of S6 kinase and S6 was identified in patient-derived cell lines under amino acid-starved condition, suggestive of constitutive hyperactivation of mTORC1 signaling. This result was validated by constitutive lysosomal localization of mTOR in patients' LCLs. Furthermore, patients' LCLs display an excessive response to slight amino acid stimulation. Our data suggest the loss-of-function nature of SZT2 mutations in the patients, and consequent hyperactivation of mTORC1 signaling in response to both amino acid starvation and stimulation in their LCLs. By these functional analyses, the pathogenicity of newly identified SZT2 variants can be determined, allowing for more detailed characterization of genotype-phenotype correlations.

DOI： 10.1371/journal.pone.0221482

Impact of low-dose irradiation and in vivo T-cell depletion on hematopoietic stem cell transplantation for non-malignant diseases using fludarabine-based reduced-intensity conditioning. Reviewed International journal Open Access

Katsutsugu Umeda, Hiromasa Yabe, Koji Kato, Kohsuke Imai, Masao Kobayashi, Yoshiyuki Takahashi, Nao Yoshida, Maho Sato, Yoji Sasahara, Keisuke Kato, Souichi Adachi, Yuhki Koga, Keiko Okada, Masami Inoue, Yoshiko Hashii, Yoshiko Atsuta, Tomohiro Morio

Bone marrow transplantation Vol. 54 ( 8 ) page： 1227 - 1236 2019.8

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

Reduced-intensity conditioning is widely used with hematopoietic stem cell transplantation for non-malignant diseases: however, the optimal conditioning to ensure stable engraftment has not been established. In this study, we retrospectively compared the impact of low-dose (1-6 Gy) irradiation and in vivo T-cell depletion on the clinical outcome of 523 patients with non-malignant disease who underwent a first allogeneic hematopoietic stem cell transplantation using fludarabine-based reduced-intensity conditioning. Use of low-dose irradiation, but not of anti-thymocyte globulin/anti-lymphocyte globulin, showed a beneficial effect on overall survival (adjusted hazard ratio: 0.56; 95% confidence interval: 0.35-0.91, P = 0.018). Furthermore, use of low-dose irradiation was strongly associated with lower transplant-related mortality (adjusted hazard ratio: 0.55; 95% confidence interval: 0.32-0.96, P = 0.034). The addition of low-dose irradiation to the conditioning regimen was beneficial, at least to the short-term clinical outcome. A large prospective study with long-term follow-up is now required to extend these findings and establish the optimal hematopoietic stem cell transplant conditioning for patients with at least some subgroups of non-malignant diseases.

DOI： 10.1038/s41409-018-0418-8

愛知県におけるチャイルド・デス・レビューの試み

沼口敦, 高橋義行, 夏目淳, 伊藤嘉規, 齋藤伸治, 吉川哲史, 奥村彰久

日本小児科学会雑誌 Vol. 123 ( 8 ) page： 1313 - 1313 2019.8

小児重症呼吸不全患者の気管支肺胞洗浄液を用いた次世代シークエンス法による病原微生物の網羅的検出

武内俊, 川田潤一, 堀場千尋, 奥村俊彦, 鈴木高子, 鳥居ゆか, 奥野友介, 高橋義行, 伊藤嘉規, 河邉慎司, 池山貴也

日本小児科学会雑誌 Vol. 123 ( 8 ) page： 1336 - 1336 2019.8

先天性嚢胞性肺疾患との鑑別に苦慮した巨大縦隔気腫の2例

本部和也, 脇田浩正, 上田一仁, 田中亮, 三浦良介, 呉尚治, 浅田英之, 北瀬悠磨, 鈴木俊彦, 兵藤玲奈, 見松はるか, 伊藤美春, 齊藤明子, 村松友佳子, 佐藤義朗, 早川昌弘, 高橋義行

日本小児科学会雑誌 Vol. 123 ( 8 ) page： 1312 - 1312 2019.8

ステロイド減量に伴い再発を繰り返した抗MOG抗体陽性急性散在性脳脊髄炎(ADEM)の1例

隈井すみれ, 山本啓之, 川口将宏, 牧祐輝, 田中雅大, 岡井佑, 坂口陽子, 中田智彦, 城所博之, 高橋義行, 夏目淳, 濱口直子, 柴田元博, 金子仁彦, 高橋利幸

日本小児科学会雑誌 Vol. 123 ( 8 ) page： 1310 - 1310 2019.8

テクノロジーの進展は検査医学をどう変えるか急性リンパ性白血病に対する次世代シークエンサーを用いた遺伝子診断およびキメラ抗原受容体遺伝子改変T(CAR-T)細胞療法

高橋義行

臨床病理 Vol. 67 ( 8 ) page： 884 - 884 2019.8

CF290 for pancolonic chromoendoscopy improved sessile serrated polyp detection and procedure time: a propensity score-matching study. Reviewed

Toyoshima O, Yoshida S, Nishizawa T, Yamakawa T, Sakitani K, Hata K, Takahashi Y, Fujishiro M, Watanabe H, Koike K

Endoscopy international open Vol. 7 ( 8 ) page： E987 - E993 2019.8

Whole abdominopelvic intensity-modulated radiation therapy for peritoneal disseminated rhabdomyosarcoma with three-year follow-up: a case report. Reviewed International journal Open Access

Mariko Kawamura, Kuniyasu Okudaira, Yoshiyuki Itoh, Takeshi Kamomae, Eri Nishikawa, Hideki Muramatsu, Yoshiyuki Takahashi, Kazuki Yokota, Shinji Naganawa

Radiation oncology (London, England) Vol. 14 ( 1 ) page： 127 - 127 2019.7

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

BACKGROUND: The role of local radiotherapy in the treatment of metastatic rhabdomyosarcoma is important. However, with peritoneal dissemination, the application of local therapy is challenging. Although there are few reports addressing the efficacy of the whole abdominopelvic irradiation to peritoneal disseminated rhabdomyosarcoma patients, no precise curse of treatment nor the follow up result is explained in paper nor in the text. CASE PRESENTATION: Six years old rhabdomyosarcoma boy with peritoneal dissemination was treated at our facility under COG D9803 protocol (vincristine, dactinomycin, and cyclophosphamide (VAC)). He underwent tumor resection on the 14th week according to the protocol. During surgery, the 2-cm residual tumor was completely resected, but in the pelvis, numerous nodules that were suspected as peritoneal disseminated tumors were observed. We administered 30 Gy/20fr whole abdominopelvic radiotherapy using volumetric modulated arc therapy (VMAT) technique and a 6 Gy sequential boost to pelvis after the surgery and completed the protocol treatment. During the course of treatment, the patient experienced G4 hematological toxicity and received multiple transfusions, particularly after whole abdominopelvic irradiation. He has achieved complete remission and is alive without evidence of recurrence and severe late adverse effect for 3 years. In terms of growth, his height and weight are within the average values for Japanese boys at the same age. CONCLUSION: By using the VMAT technique, a patient with peritoneal disseminated rhabdomyosarcoma can be treated, and a dose of 30 Gy to the whole abdominopelvis with concurrent chemotherapy may be tolerable.

DOI： 10.1186/s13014-019-1333-x

Comparison of Clinical Characteristics of Human Metapneumovirus and Respiratory Syncytial Virus Infections in Hospitalized Young Children. Reviewed Open Access

Akinobu Taniguchi, Jun-Ichi Kawada, Kiyotaka Go, Naozumi Fujishiro, Yosuke Hosokawa, Yuki Maki, Yuichiro Sugiyama, Michio Suzuki, Takeshi Tsuji, Shin Hoshino, Hideki Muramatsu, Hiroyuki Kidokoro, Fumie Kinoshita, Akihiro Hirakawa, Yoshiyuki Takahashi, Yoshiaki Sato, Jun Natsume

Japanese journal of infectious diseases Vol. 72 ( 4 ) page： 237 - 242 2019.7

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

Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are the leading causes of acute respiratory tract infection in children, and clinical manifestations of these virus infections are considered similar. To investigate the differences in clinical characteristics between HMPV and RSV infections in young children, we prospectively enrolled children ＜ 3 years old who required hospitalization with acute respiratory tract infection due to HMPV or RSV at 10 hospitals in Japan. We enrolled 48 children with HMPV infection and 141 with RSV infection. Patients with HMPV infection were older than those with RSV infection. High-grade fever was more frequently observed in patients with HMPV infection, whereas no significant differences in respiratory symptoms were apparent. Abnormal serum lactate dehydrogenase values and consolidation shadows on chest X-ray were more frequently observed in patients with HMPV infection. During hospitalization, nasal mucus suction was more frequently required in patients with RSV infection. On the other hand, β2-adrenergic agonists, corticosteroids, and leukotriene receptor antagonists were more frequently used in patients with HMPV infection. These findings suggest that HMPV and RSV infections show similar respiratory symptoms, but HMPV infection is more likely to lead to the development of pneumonia, at least among hospitalized young children.

DOI： 10.7883/yoken.JJID.2018.480

Relationship between plasma rabbit anti-thymocyte globulin level and response to immunosuppressive therapy in patients with severe aplastic anemia: Results of a multicenter, prospective, randomized study

Effects of HLA mismatch on cytomegalovirus reactivation in cord blood transplantation Open Access

Yokoyama, H; Kanda, J; Kato, S; Kondo, E; Maeda, Y; Saji, H; Takahashi, S; Onizuka, M; Onishi, Y; Ozawa, Y; Kanamori, H; Ishikawa, J; Ohno, Y; Ichinohe, T; Takanashi, M; Kato, K; Atsuta, Y; Kanda, Y; Ikegame, K; Utsunomiya, A; Kawase, T; Kim, SW; Kuwatsuka, Y; Kobayashi, T; Takatsuka, Y; Takahashi, Y; Tanaka, J; Tamaki, H; Tsuji, M; Nishida, T; Masuko, M; Matsuno, R; Murata, M; Morishima, S; Morishima, Y; Yokoyama, H; Wake, A; Watanabe, N; Ashida, T; Hoshino, T; Yabe, T; Sakamoto, K; Fuji, S; Miyamura, K; Arima, N; Kondo, E; Yoshimitsu, M; Kawamura, K; Kawata, T; Kishimoto, K; Tatara, R; Hagino, T; Fujiwara, SI; Shimomura, Y; Sakaguchi, H; Hirabayashi, S; Ishii, H; Onda, Y; Kato, I; Kawajiri, A; Shindo, T; Tokunaga, M; Nonami, A; Muranushi, H; Yoshinaga, N; Kawashima, N; Shiratori, S; Tada, Y; Tanoue, SU; Hirayama, M; Fukunaga, K; Ohbiki, M

BONE MARROW TRANSPLANTATION Vol. 54 ( 7 ) page： 1004 - 1012 2019.7

Narita, A; Muramatsu, H; Xu, YY; Nishikawa, E; Kawashima, N; Okuno, Y; Nishio, N; Hama, A; Yamazaki, H; Nakao, S; Kojima, S; Takahashi, Y

BONE MARROW TRANSPLANTATION Vol. 54 page： 29 - 29 2019.7

Narita Atsushi, Muramatsu Hideki, Xu Yinyan, Nishikawa Eri, Kawashima Nozomu, Okuno Yusuke, Nishio Nobuhiro, Hama Asahito, Yamazaki Hirohito, Nakao Shinji, Kojima Seiji, Takahashi Yoshiyuki

BONE MARROW TRANSPLANTATION Vol. 54 page： 29-29 2019.7

MYCN de novo gain-of-function mutation in a patient with a novel megalencephaly syndrome. Reviewed International journal

Kohji Kato, Fuyuki Miya, Nanako Hamada, Yutaka Negishi, Yoko Narumi-Kishimoto, Hiroshi Ozawa, Hidenori Ito, Ikumi Hori, Ayako Hattori, Nobuhiko Okamoto, Mitsuhiro Kato, Tatsuhiko Tsunoda, Yonehiro Kanemura, Kenjiro Kosaki, Yoshiyuki Takahashi, Koh-Ichi Nagata, Shinji Saitoh

Journal of medical genetics Vol. 56 ( 6 ) page： 388 - 395 2019.6

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

BACKGROUND: In this study, we aimed to identify the gene abnormality responsible for pathogenicity in an individual with an undiagnosed neurodevelopmental disorder with megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly and neuroblastoma. We then explored the underlying molecular mechanism. METHODS: Trio-based, whole-exome sequencing was performed to identify disease-causing gene mutation. Biochemical and cell biological analyses were carried out to elucidate the pathophysiological significance of the identified gene mutation. RESULTS: We identified a heterozygous missense mutation (c.173C>T; p.Thr58Met) in the MYCN gene, at the Thr58 phosphorylation site essential for ubiquitination and subsequent MYCN degradation. The mutant MYCN (MYCN-T58M) was non-phosphorylatable at Thr58 and subsequently accumulated in cells and appeared to induce CCND1 and CCND2 expression in neuronal progenitor and stem cells in vitro. Overexpression of Mycn mimicking the p.Thr58Met mutation also promoted neuronal cell proliferation, and affected neuronal cell migration during corticogenesis in mouse embryos. CONCLUSIONS: We identified a de novo c.173C>T mutation in MYCN which leads to stabilisation and accumulation of the MYCN protein, leading to prolonged CCND1 and CCND2 expression. This may promote neurogenesis in the developing cerebral cortex, leading to megalencephaly. While loss-of-function mutations in MYCN are known to cause Feingold syndrome, this is the first report of a germline gain-of-function mutation in MYCN identified in a patient with a novel megalencephaly syndrome similar to, but distinct from, CCND2-related megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. The data obtained here provide new insight into the critical role of MYCN in brain development, as well as the consequences of MYCN defects.

DOI： 10.1136/jmedgenet-2018-105487

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

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

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

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

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

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-Helicobacter pylori antibody titer and Kyoto classification score could provide a more accurate diagnosis of H pylori. 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

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

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

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

Planetary-scale streak structure reproduced in high-resolution simulations of the Venus atmosphere with a low-stability layer Reviewed Open Access

Hiroki Kashimura, Norihiko Sugimoto, Masahiro Takagi, Yoshihisa Matsuda, Wataru Ohfuchi, Takeshi Enomoto, Kensuke Nakajima, Masaki Ishiwatari, Takao M. Sato, George L. Hashimoto, Takehiko Satoh, Yoshiyuki O. Takahashi, Yoshi-Yuki Hayashi

NATURE COMMUNICATIONS Vol. 10 ( 1 ) page： 23 2019.1

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Cloud patterns are important clues for revealing the atmospheric circulation of Venus. Recently, a planetary-scale streak structure has been discovered in middle- and lower-cloud images of Venus' night-side taken by IR2, the 2-mu m camera, on board the Akatsuki orbiter. However, its formation mechanism has not been investigated. Here we succeed, for the first time, in reproducing the patterns of the observed streak structure, as regions of strong downward flows that develop in high-resolution global simulations of the Venus atmosphere. The streaks are formed in both hemispheres with equatorial symmetry, which is caused by equatorial Rossby-like and Kelvin-like waves with zonal wavenumber one. The low-stability layer that has been suggested by past observations is essential for reproducing the streak structure. The streaks of downward flow result from the interaction of the meridionally tilted phase lines of the Rossby-like waves and the characteristics of baroclinic instability produced around the low-stability layer.

DOI： 10.1038/s41467-018-07919-y

Investigation of appropriate semi-quantitative index for assessment of esophageal and breast cancer treatment response in Japanese patients using 18F-FDG PET/CT findings. Reviewed

Tsuchitani T, Takahashi Y, Maeda Y, Oda M, Enoki T, Kotoura N, Kitajima K

Hellenic journal of nuclear medicine Vol. 22 ( 1 ) page： 20 - 24 2019.1

A novel CUL4B splice site variant in a young male exhibiting less pronounced features. Reviewed International journal

Yuji Nakamura, Yusuke Okuno, Hideki Muramatsu, Tomoko Kawai, Kazuhito Satou, Daisuke Ieda, Ikumi Hori, Kei Ohashi, Yutaka Negishi, Ayako Hattori, Yoshiyuki Takahashi, Seiji Kojima, Shinji Saitoh

Human genome variation Vol. 6 page： 43 - 43 2019

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

Patients with variants in CUL4B exhibit syndromic intellectual disability (MIM #300354). A seven-year-old boy presented with intellectual disability, a history of seizure, characteristic facial features, and short stature. Whole-exome sequencing detected a c.974+3A>G variant in CUL4B, which was subsequently confirmed to disrupt mRNA splicing. The current patient showed less pronounced phenotypic features compared with the previously reported cases. This report, therefore, provides evidence of genotype-phenotype correlations in CUL4B-related disorders.

DOI： 10.1038/s41439-019-0074-6

[LOCALIZED AMYLOIDOSIS OF THE RENAL SINUS: A CASE REPORT].

Ohashi T, Tanaka J, Asai K, Shimada S, Takahashi Y, Furukawa T

Nihon Hinyokika Gakkai zasshi. The japanese journal of urology Vol. 110 ( 3 ) page： 191 - 195 2019

Ureteral dilatation detected in magnetic resonance imaging predicts vesicoureteral reflux in children with urinary tract infection. Reviewed International journal Open Access

Norihiro Murakami, Jun-Ichi Kawada, Azumi Watanabe, Toshinao Arakawa, Takamasa Kano, Takako Suzuki, Ryo Tanaka, Daiei Kojima, Yoshihiko Kawano, Shin Hoshino, Hideki Muramatsu, Yoshiyuki Takahashi, Yoshiaki Sato, Masashi Koyama, Jun Natsume

PloS one Vol. 13 ( 12 ) page： e0209595 2018.12

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

OBJECTIVE: Urinary tract infection (UTI), one of the most common bacterial infections occurring during infancy and early childhood, is frequently associated with vesicoureteral reflux (VUR). Although several guidelines recommend performing ultrasonography as a screening test, its utility is not adequate and appropriate screening tests are strongly desirable. In this study, we evaluate the use of magnetic resonance imaging (MRI) as a screening test for VUR in children with UTI. METHODS: We prospectively studied 108 patients with suspected UTI between April 2014 and March 2016. UTI was diagnosed on the basis of diffusion-weighted MRI (DW-MRI) and urine culture findings. We measured ureteral dilatation using MRI in 96 patients with UTI and assessed the relationship between ureteral dilatation in MRI and VUR in 46 patients who underwent voiding cystourethrography (VCUG). RESULTS: Among 108 patients, 88 and 8 were diagnosed with upper and lower UTI, respectively. Among 46 patients who underwent VCUG, 23 had VUR (14 low grade and 9 high grade). Patients with ureteral dilatation detected on MRI had VUR more frequently than those without ureteral dilatation (any grades VUR, 71% vs. 32%; P = 0.02; high-grade VUR, 38% vs. 2%, P = 0.007). Overall, ureteral dilatation findings on MRI achieved sensitivity 65.2% and specificity 73.9% as a screening test for VUR. In addition, DW-MRI achieved sensitivity 100% and specificity 81.8% in the diagnosis of upper UTI. CONCLUSION: These findings suggested that MRI is a valuable tool for screening of VUR as well as diagnosis of upper UTI.

DOI： 10.1371/journal.pone.0209595

Identification of potential pathogenic viruses in patients with acute myocarditis using next-generation sequencing. Reviewed International journal

Suguru Takeuchi, Jun-Ichi Kawada, Yusuke Okuno, Kazuhiro Horiba, Takako Suzuki, Yuka Torii, Kazushi Yasuda, Atsushi Numaguchi, Taichi Kato, Yoshiyuki Takahashi, Yoshinori Ito

Journal of medical virology Vol. 90 ( 12 ) page： 1814 - 1821 2018.12

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

Myocarditis is an inflammatory disease of the myocardium and leads to cardiac dysfunction and heart failure. Although viral infections are considered to be the most common etiology of myocarditis, the identification of the causative virus is still challenging. Recently, next-generation sequencing (NGS) has been applied in the diagnosis of infectious diseases. The aim of the current study was to comprehensively analyze potential pathogenic microorganisms using NGS in the sera of patients with myocarditis. Twelve pediatric and five adult patients hospitalized for acute myocarditis were included. Serum samples in the acute phase were obtained and analyzed using NGS to detect pathogen-derived DNA and RNA. Viral sequence reads were detected in 7 (41%) of the 17 myocarditis patients by NGS. Among these patients, detection of Epstein-Barr virus, human parvovirus B19, torque teno virus, and respiratory syncytial virus reads by NGS was consistent with polymerase chain reaction or antigen test results in one patient each. A large number of human pegivirus reads were detected from one patient by RNA sequencing; however, its pathogenicity to human is unknown. Conversely, the number of detected virus-derived reads was small in most cases, and the pathophysiological role of these viruses remains to be clarified. No significant bacterial or fungal reads other than normal bacterial flora was detected. These data indicate that comprehensive detection of virus-derived DNA and RNA using NGS can be useful for the identification of potential pathogenic viruses in myocarditis.

DOI： 10.1002/jmv.25263

Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency. Reviewed International journal Open Access

Takuya Takeichi, Yusuke Okuno, Akane Kawamoto, Takeshi Inoue, Eiko Nagamoto, Chiaki Murase, Eri Shimizu, Kenichi Tanaka, Yuichi Kageshita, Satoshi Fukushima, Michihiro Kono, Junko Ishikawa, Hironobu Ihn, Yoshiyuki Takahashi, Masashi Akiyama

Journal of lipid research Vol. 59 ( 12 ) page： 2413 - 2420 2018.12

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

Neu-Laxova syndrome (NLS) is a very rare autosomal recessive congenital disorder characterized by disturbed development of the central nervous system and the skin and caused by mutations in any of the three genes involved in de novo l-serine biosynthesis: PHGDH, PSAT1, and PSPH l-Serine is essential for the biosynthesis of phosphatidylserine and sphingolipids. The extracellular lipid of the stratum corneum, of which sphingolipid constitutes a significant part, plays a primary role in skin barrier function. Here, we describe a Japanese NLS pedigree with a previously unreported nonsense mutation in PHGDH and a unique inversion of chromosome 1. In addition, the levels of 11 major ceramide classes in the tape-stripped stratum corneum of the NLS patient's skin were assessed by LC/MS. Notably, lower amounts of ceramides of all classes were found in the patient's stratum corneum than in those of controls. This is the first report to demonstrate the reduction of ceramides in the stratum corneum of an NLS patient due to PHGDH mutations. The clinical findings and a detailed analysis of ceramides from the stratum corneum in the family extend the spectrum of clinical anomalies and give us a clue to the pathomechanisms of ichthyosis in NLS patients with phosphoglycerate dehydrogenase deficiency.

DOI： 10.1194/jlr.P087536

The presence of defective Epstein-Barr virus (EBV) infection in EBV-associated hematological malignancies

Okuno, Y; Murata, T; Sato, Y; Ito, Y; Yoshida, K; Sawada, A; Shiraishi, Y; Miyano, S; Takahashi, Y; Kojima, S; Ogawa, S; Kimura, H

CANCER SCIENCE Vol. 109 page： 642 - 642 2018.12

The presence of defective Epstein-Barr virus (EBV) infection in EBV-associated hematological malignancies

Okuno Yusuke, Murata Takayuki, Sato Yoshitaka, Ito Yoshinori, Yoshida Kenichi, Sawada Akihisa, Shiraishi Yuichi, Miyano Satoru, Takahashi Yoshiyuki, Kojima Seiji, Ogawa Seishi, Kimura Hiroshi

CANCER SCIENCE Vol. 109 page： 642-642 2018.12

Clinical and Genetic Characteristics of Patients with Shwachman-Diamond Syndrome in Japan Open Access

Watanabe Kenichiro, Kanegane Hirokazu, Hamabata Takayuki, Kozuki Kagehiro, Umeda Katsutsugu, Ueno Hiroo, Yoshida Kenichi, Hama Asahito, Okuno Yusuke, Muramatsu Hideki, Takahashi Yoshiyuki, Hasegawa Daisuke, Manabe Atsushi, Ohara Akira, Ito Masafumi, Ogawa Seishi, Kojima Seiji, Ito Etsuro

BLOOD Vol. 132 2018.11

Combination of TREC Measurement and Next-Generation Sequencing in Newborn Screening for Severe Combined Immunodeficiency: A Pilot Program in Japan Open Access

Muramatsu Hideki, Kojima Daiei, Okuno Yusuke, Kataoka Shinsuke, Nakajima Yoko, Ito Tetsuya, Tsuge Ikuya, Yoshimi Sakai, Kato Tomoaki, Kojima Seiji, Takahashi Yoshiyuki

BLOOD Vol. 132 2018.11

Piggybac CD19 CAR T Cells Eradicate CNS Leukemia By Direct Delivery into Cerebral Ventricle of Xenograft Mice Model Open Access

Tanaka, K; Kato, I; Tanaka, M; Morita, D; Takahashi, Y; Nakahata, T; Umeda, K; Hiramatsu, H; Adachi, S; Takita, J; Nakazawa, Y

BLOOD Vol. 132 2018.11

Randomized Trial of Two Dosages of Rabbit Antithymocyte Globulin in Patients with Aplastic Anemia Open Access

Narita, A; Zhu, XF; Muramatsu, H; Chen, XJ; Guo, Y; Yang, WY; Zhang, JL; Liu, F; Jang, JH; Kook, H; Kim, H; Usuki, K; Yamazaki, H; Takahashi, Y; Nakao, S; Lee, JW; Kojima, S

BLOOD Vol. 132 2018.11

The Presence of Defective Epstein-Barr Virus (EBV) Infection in Patients with EBV-Associated Hematological Malignancy

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

BLOOD Vol. 132 2018.11

Application of RNA Sequencing for Early Diagnosis of NUT Carcinoma: A Case Report

Miwata Shunsuke, Narita Atsushi, Wakamatsu Manabu, Narita Kotaro, Kitazawa Hironobu, Kataoka Shinsuke, Hamada Motoharu, Murakami Norihiro, Taniguchi Rieko, Ichikawa Daisuke, Suzuki Kyogo, Kawashima Nozomu, Nishikawa Eri, Okuno Yusuke, Nishio Nobuhiro, Muramatsu Hideki, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 65 page： S74 - S74 2018.11

A Case of Thoracic Tumor Caused by SMARCA4 Biallelic Inactivation

Ichikawa Daisuke, Muramatsu Hideki, Okuno Yusuke, Wakamatsu Manabu, Miwata Shunsuke, Narita Kotaro, Kitazawa Hironobu, Hamada Motoharu, Kataoka Shinsuke, Taniguchi Rieko, Murakami Norihiro, Suzuki Kyogo, Nishikawa Eri, Kawashima Nozomu, Narita Atsushi, Nishio Nobuhiro, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 65 page： S74 - S74 2018.11

A Case of MLL-AF9 Fusion Positive Malignant Lymphoma Without Bone Marrow Infiltration Either at First Diagnosis or at Relapse

Narita Kotaro, Kataoka Shinsuke, Hamada Motoharu, Ichikawa Daisuke, Taniguchi Rieko, Murakami Norihiro, Suzuki Kyogo, Nishikawa Eri, Nishio Nobuhiro, Okuno Yusuke, Kawashima Nozomu, Narita Atsushi, Muramatsu Hideki, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 65 page： S99 - S99 2018.11

A Case of Dyskeratosis Congenital who Showed the Improvement of Telomere Length After Receiving Androgens for 11 Years

Wakamatsu Manabu, Nishio Nobuhiro, Miwata Shunsuke, Narita Kotaro, Kitazawa Hironobu, Kataoka Shinsuke, Hamada Motoharu, Murakami Norihiro, Ichikawa Daisuke, Taniguchi Rieko, Suzuki Kyogo, Kawashima Nozomu, Nishikawa Eri, Okuno Yusuke, Narita Atsushi, Muramatsu Hideki, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 65 page： S65 - S65 2018.11

Diagnosis of Inherited Bone Marrow Failure Syndromes Using Sequencing Approaches

Narita, A; Muramatsu, H; Okuno, Y; Yoshida, K; Shiraishi, Y; Sakaguchi, H; Kawashima, N; Wang, XA; Xu, YY; Chiba, K; Tanaka, H; Hama, A; Sanada, M; Hitoshi, K; Yamaguchi, H; Ohga, S; Manabe, A; Harigae, H; Kunishima, S; Ishii, E; Kobayashi, M; Koike, K; Watanabe, K; Ito, E; Takata, M; Yabe, M; Ogawa, S; Miyano, S; Kojima, S; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 65 page： S7 - S7 2018.11

Disappearance of Minimal Residual Disease Demonstrates Graft Versus Neuroblastoma Effect After KIR-Ligand Mismatched Allogeneic Cord Blood Transplantation

Nishio, N; Kataoka, S; Miwata, S; Narita, K; Kitazawa, H; Hamada, M; Ichikawa, D; Taniguchi, R; Murakami, N; Suzuki, K; Kawashima, N; Nishikawa, E; Okuno, Y; Narita, A; Muramatsu, H; Kojima, S; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 65 page： S8 - S8 2018.11

Herpesvirus Infection in Pediatric Autologous Hematopoietic Stem Cell Transplantation

Miura, H; Kudo, K; Tanaka, M; Takahashi, Y; Kojima, S; Yoshikawa, T

PEDIATRIC BLOOD & CANCER Vol. 65 page： S60 - S61 2018.11

Unmet Medical Needs for Japanese Kampo Medicine in Children with Hematological and Oncological Disease

Kawashima, N; Miwata, S; Narita, K; Kataoka, S; Hamada, M; Murakami, N; Ichikawa, D; Suzuki, K; Kitazawa, H; Nishikawa, E; Okuno, Y; Taniguchi, R; Narita, A; Muramatsu, H; Nishio, N; Kojima, S; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 65 page： S33 - S33 2018.11

Urgent Successful HLA-Haploidentical Stem Cell Transplantation in Children with Aplastic Anemia Considering Upfront SCT Strategy

Nishikawa, E; Wakamatsu, M; Miwata, S; Narita, K; Murakami, N; Kataoka, S; Hamada, M; Ichikawa, D; Kitazawa, H; Taniguchi, R; Suzuki, K; Kawashima, N; Okuno, Y; Narita, A; Muramatsu, H; Nishio, N; Kojima, S; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 65 page： S65 - S66 2018.11

Morphological Features of Bone Marrow in Patients with Inherited Bone Marrow Failure

Hama, A; Hasegawa, D; Manabe, A; Nozawa, K; Narita, A; Okuno, Y; Muramatsu, H; Takahashi, Y; Watanabe, K; Ohara, A; Ito, M; Kojima, S

PEDIATRIC BLOOD & CANCER Vol. 65 page： S66 - S66 2018.11

NGS-Based Methylation Analysis of Juvenile Myelomonocytic Leukemia using the Digital Restriction Enzyme Analysis of Methylation (DREAM) Method

Kitazawa, H; Murakami, N; Okuno, Y; Muramatsu, H; Wakamatsu, M; Miwata, S; Narita, K; Kataoka, S; Hamada, M; Ichikawa, D; Taniguchi, R; Suzuki, K; Kawashima, N; Nishikawa, E; Narita, A; Nishio, N; Kojima, S; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 65 page： S22 - S23 2018.11

Relapse After Spontaneous Molecular Remission in a Female with Congenital Acute Myeloid Leukemia with KAT6A-EP300 Fusion Transcript

Taniguchi, R; Kawashima, N; Ikawa, Y; Wakamatsu, M; Miwata, S; Narita, K; Kataoka, S; Hamada, M; Murakami, N; Ichikawa, D; Kitazawa, H; Suzuki, K; Nishikawa, E; Narita, A; Okuno, Y; Muramatsu, H; Nishio, N; Nishimura, R; Kojima, S; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 65 page： S98 - S98 2018.11

Urgent Successful HLA-Haploidentical Stem Cell Transplantation in Children with Aplastic Anemia Considering Upfront SCT Strategy

Nishikawa Eri, Wakamatsu Manabu, Miwata Shunsuke, Narita Kotaro, Murakami Norihiro, Kataoka Shinsuke, Hamada Motoharu, Ichikawa Daisuke, Kitazawa Hironobu, Taniguchi Rieko, Suzuki Kyogo, Kawashima Nozomu, Okuno Yusuke, Narita Atsushi, Muramatsu Hideki, Nishio Nobuhiro, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 65 page： S65-S66 2018.11

Unmet Medical Needs for Japanese Kampo Medicine in Children with Hematological and Oncological Disease

Kawashima Nozomu, Miwata Shunsuke, Narita Kotaro, Kataoka Shinsuke, Hamada Motoharu, Murakami Norihiro, Ichikawa Daisuke, Suzuki Kyogo, Kitazawa Hironobu, Nishikawa Eri, Okuno Yusuke, Taniguchi Rieko, Narita Atsushi, Muramatsu Hideki, Nishio Nobuhiro, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 65 page： S33-S33 2018.11

Relapse After Spontaneous Molecular Remission in a Female with Congenital Acute Myeloid Leukemia with KAT6A-EP300 Fusion Transcript

Taniguchi Rieko, Kawashima Nozomu, Ikawa Yasuhiro, Wakamatsu Manabu, Miwata Shunsuke, Narita Kotaro, Kataoka Shinsuke, Hamada Motoharu, Murakami Norihiro, Ichikawa Daisuke, Kitazawa Hironobu, Suzuki Kyogo, Nishikawa Eri, Narita Atsushi, Okuno Yusuke, Muramatsu Hideki, Nishio Nobuhiro, Nishimura Ryosei, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 65 page： S98-S98 2018.11

Morphological Features of Bone Marrow in Patients with Inherited Bone Marrow Failure

Hama Asahito, Hasegawa Daisuke, Manabe Atsushi, Nozawa Kazue, Narita Atsushi, Okuno Yusuke, Muramatsu Hideki, Takahashi Yoshiyuki, Watanabe Kenichiro, Ohara Akira, Ito Masafumi, Kojima Seiji

PEDIATRIC BLOOD & CANCER Vol. 65 page： S66-S66 2018.11

NGS-Based Methylation Analysis of Juvenile Myelomonocytic Leukemia using the Digital Restriction Enzyme Analysis of Methylation (DREAM) Method

Kitazawa Hironobu, Murakami Norihiro, Okuno Yusuke, Muramatsu Hideki, Wakamatsu Manabu, Miwata Shunsuke, Narita Kotaro, Kataoka Shinsuke, Hamada Motoharu, Ichikawa Daisuke, Taniguchi Rieko, Suzuki Kyogo, Kawashima Nozomu, Nishikawa Eri, Narita Atsushi, Nishio Nobuhiro, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 65 page： S22-S23 2018.11

Disappearance of Minimal Residual Disease Demonstrates Graft Versus Neuroblastoma Effect After KIR-Ligand Mismatched Allogeneic Cord Blood Transplantation

Nishio Nobuhiro, Kataoka Shinsuke, Miwata Shunsuke, Narita Kotaro, Kitazawa Hironobu, Hamada Motoharu, Ichikawa Daisuke, Taniguchi Rieko, Murakami Norihiro, Suzuki Kyogo, Kawashima Nozomu, Nishikawa Eri, Okuno Yusuke, Narita Atsushi, Muramatsu Hideki, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 65 page： S8-S8 2018.11

Compound heterozygous RYR1 mutations by whole exome sequencing in a family with three repeated affected fetuses with fetal akinesia. Reviewed

Suzumori N, Inagaki H, Ohtani A, Kumagai K, Takeda E, Yoshihara H, Sawada Y, Inuzuka S, Iwagaki S, Takahashi Y, Kurahashi H, Sugiura-Ogasawara M

European journal of obstetrics, gynecology, and reproductive biology Vol. 230 page： 200 - 202 2018.11

Diagnosis of Inherited Bone Marrow Failure Syndromes Using Sequencing Approaches

Narita Atsushi, Muramatsu Hideki, Okuno Yusuke, Yoshida Kenichi, Shiraishi Yuichi, Sakaguchi Hirotoshi, Kawashima Nozomu, Wang Xinan, Xu Yinyan, Chiba Kenichi, Tanaka Hiroko, Hama Asahito, Sanada Masashi, Hitoshi Kanno, Yamaguchi Hiroki, Ohga Shouichi, Manabe Atsushi, Harigae Hideo, Kunishima Shinji, Ishii Eiichi, Kobayashi Masao, Koike Kenichi, Watanabe Kenichiro, Ito Etsuro, Takata Minoru, Yabe Miharu, Ogawa Seishi, Miyano Satoru, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 65 page： S7-S7 2018.11

Application of RNA Sequencing for Early Diagnosis of NUT Carcinoma: A Case Report

PEDIATRIC BLOOD & CANCER Vol. 65 page： S74-S74 2018.11

A Case of Dyskeratosis Congenital who Showed the Improvement of Telomere Length After Receiving Androgens for 11 Years

PEDIATRIC BLOOD & CANCER Vol. 65 page： S65-S65 2018.11

A Case of MLL-AF9 Fusion Positive Malignant Lymphoma Without Bone Marrow Infiltration Either at First Diagnosis or at Relapse

PEDIATRIC BLOOD & CANCER Vol. 65 page： S99-S99 2018.11

A Case of Thoracic Tumor Caused by SMARCA4 Biallelic Inactivation

PEDIATRIC BLOOD & CANCER Vol. 65 page： S74-S74 2018.11

骨髄MRDの消失は神経芽腫に対するKIRリガンド不一致同種臍帯血移植後の移植片対腫瘍効果を示唆する(Disappearance of minimal residual disease demonstrates graft versus neuroblastoma effect after KIR-ligand mismatched allogeneic cord blood transplantation)

日本小児血液・がん学会雑誌 Vol. 55 ( 4 ) page： 154 - 154 2018.10

自然寛解後に再発をきたしたKAT6A-EP300融合転写を伴う先天性急性骨髄性白血病(Relapse after spontaneous molecular remission in a female with congenital acute myeloid leukemia with KAT6A-EP300 fusion transcript)

日本小児血液・がん学会雑誌 Vol. 55 ( 4 ) page： 314 - 314 2018.10

蛋白同化ステロイド内服を11年継続している先天性角化不全症の一例(A case of dyskeratosis congenital who showed the improvement of telomere length after receiving androgens for 11 years)

日本小児血液・がん学会雑誌 Vol. 55 ( 4 ) page： 246 - 246 2018.10

小児再生不良性貧血に対するUpfront移植を含むハプロ移植の7例(Urgent successful HLA-haploidentical stem cell transplantation in children with aplastic anemia considering upfront SCT strategy)

日本小児血液・がん学会雑誌 Vol. 55 ( 4 ) page： 247 - 247 2018.10

シーケンスによる先天性骨髄不全症の診断(Diagnosis of Inherited Bone Marrow Failure Syndromes Using Sequencing Approaches)

Narita Atsushi, Muramatsu Hideki, Okuno Yusuke, Yoshida Kenichi, Shiraishi Yuichi, Sakaguchi Hirotoshi, Kawashima Nozomu, Wang Xinan, Xu Yinyan, Chiba Kenichi, Tanaka Hiroko, Hama Asahito, Sanada Masashi, Kanno Hitoshi, Yamaguchi Hiroki, Ohga Shouichi, Manabe Atsushi, Harigae Hideo, Kunishima Shinji, Ishii Eiichi, Kobayashi Masao, Koike Kenichi, Watanabe Kenichiro, Ito Etsuro, Takata Minoru, Yabe Miharu, Ogawa Seishi, Miyano Satoru, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 55 ( 4 ) page： 153 - 153 2018.10

初発時および再発時に骨髄浸潤を認めなかったMLL/AF9融合遺伝子を持つ悪性リンパ腫の1例(A case of MLL-AF9 fusion positive malignant lymphoma without bone marrow infiltration either at first diagnosis or at relapse)

日本小児血液・がん学会雑誌 Vol. 55 ( 4 ) page： 316 - 316 2018.10

小児がん拠点病院単一施設における漢方診療の患者ニーズ調査(Unmet medical needs for Japanese Kampo medicine in children with hematological and oncological disease)

日本小児血液・がん学会雑誌 Vol. 55 ( 4 ) page： 219 - 219 2018.10

SMARCA4の不活化変異により発症した胸部腫瘍の1例(A case of thoracic tumor caused by SMARCA4 biallelic inactivation)

日本小児血液・がん学会雑誌 Vol. 55 ( 4 ) page： 255 - 255 2018.10

RNAシーケンスが早期診断に有用であったNUT carcinomaの1例(Application of RNA sequencing for early diagnosis of NUT carcinoma: a case report)

日本小児血液・がん学会雑誌 Vol. 55 ( 4 ) page： 255 - 255 2018.10

DREAM法を用いた若年性骨髄単球性白血病に対するメチル化解析(NGS-based methylation analysis of juvenile myelomonocytic leukemia using the digital restriction enzyme analysis of methylation(DREAM) method)

日本小児血液・がん学会雑誌 Vol. 55 ( 4 ) page： 206 - 206 2018.10

Defibrotide for Prophylaxis of Hepatic Veno-Occlusive Disease Hematopoietic Stem Cell Transplantation: Results from the Japanese Prophylactic Use, Phase II, Randomized Trial

Kikuta, A; Fukuda, T; Ohashi, K; Taniguchi, S; Asano-Mori, Y; Horibe, K; Goto, H; Nakamae, H; Ogawa, H; Tamaki, H; Takahashi, Y; Kimura, T; Yoshimura, K; Umemura, K; Ogawa, C

BONE MARROW TRANSPLANTATION Vol. 53 page： 316 - 317 2018.9

Defibrotide for Treatment of Hepatic Veno-Occlusive Disease Following Hematopoietic Stem Cell Transplantation: Results from the Japanese Therapeutic Use Protocol

Kikuta, A; Fukuda, T; Ohashi, K; Taniguchi, S; Asano-Mori, Y; Horibe, K; Goto, H; Nakamae, H; Ogawa, H; Tamaki, H; Takahashi, Y; Kimura, T; Yoshimura, K; Umemura, K; Ogawa, C

BONE MARROW TRANSPLANTATION Vol. 53 page： 318 - 319 2018.9

Updated Treatment Algorism for Children with Acquired Aplastic Anemia: A Report from the Japan Childhood Aplastic Anemia Study Group

Yoshida, N; Narita, A; Muramatsu, H; Kobayashi, R; Yabe, H; Kudo, K; Yagasaki, H; Watanabe, K; Morimoto, A; Ito, E; Ohga, S; Ohara, A; Takahashi, Y; Kojima, S

BONE MARROW TRANSPLANTATION Vol. 53 page： 34 - 35 2018.9

Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia. Reviewed

Motoharu Hamada, Sayoko Doisaki, Yusuke Okuno, Hideki Muramatsu, Asahito Hama, Nozomu Kawashima, Atsushi Narita, Nobuhiro Nishio, Kenichi Yoshida, Hitoshi Kanno, Atsushi Manabe, Takashi Taga, Yoshiyuki Takahashi, Satoru Miyano, Seishi Ogawa, Seiji Kojima

International journal of hematology Vol. 108 ( 3 ) page： 306 - 311 2018.9

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

Congenital dyserythropoietic anemia (CDA) is a heterogeneous group of rare congenital disorders characterized by ineffective erythropoiesis and dysplastic changes in erythroblasts. Diagnosis of CDA is based primarily on the morphology of bone marrow erythroblasts; however, genetic tests have recently become more important. Here, we performed genetic analysis of 10 Japanese patients who had been diagnosed with CDA based on laboratory findings and morphological characteristics. We examined 10 CDA patients via central review of bone marrow morphology and genetic analysis for congenital bone marrow failure syndromes. Sanger sequencing for CDAN1, SEC23B, and KLF1 was performed for all patients. We performed whole-exome sequencing in patients without mutation in these genes. Three patients carried pathogenic CDAN1 mutations, whereas no SEC23B mutations were identified in our cohort. WES unexpectedly identified gene mutations known to cause congenital hemolytic anemia in two patients: canonical G6PD p.Val394Leu mutation and SPTA1 p.Arg28His mutation. Comprehensive genetic analysis is warranted for more effective diagnosis of patients with suspected CDA.

DOI： 10.1007/s12185-018-2482-7

Risk Factors for Viral Infections in Pediatric Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Narita, A; Ito, Y; Torii, Y; Kawada, JI; Miwata, S; Narita, K; Kitazawa, H; Hamada, M; Kataoka, S; Ichikawa, D; Ito, R; Murakami, N; Kojima, D; Suzuki, K; Nishikawa, E; Kawashima, N; Okuno, Y; Muramatsu, H; Hama, A; Kojima, S; Takahashi, Y

BONE MARROW TRANSPLANTATION Vol. 53 page： 588 - 589 2018.9

Serum anti-Helicobacter pylori antibody titer and its association with gastric nodularity, atrophy, and age: A cross-sectional study. Reviewed International journal Open Access

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

World journal of gastroenterology Vol. 24 ( 35 ) page： 4061 - 4068 2018.9

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

AIM: To clarify the role of serum anti-Helicobacter pylori (H. pylori) antibody titers in gastric cancer. METHODS: In this cross-sectional study, the effect of patients' baseline characteristics and endoscopic findings on their serum antibody titers were assessed. We evaluated consecutive patients who underwent esophagogastroduodenoscopy and their first evaluation for H. pylori infection using a serum antibody test. We excluded patients with a history of eradication therapy. The participants were divided into four groups according to their E-plate serum antibody titer. Patients with serum antibody titers < 3, 3-9.9, 10-49.9, and ≥ 50 U/mL were classified into groups A, B, C, and D, respectively. RESULTS: In total, 874 participants were analyzed with 70%, 16%, 8.7%, and 5.1% of them in the groups A, B, C, and D, respectively. Patients in group C were older than patients in groups A and B. Gastric open-type atrophy, intestinal metaplasia, enlarged folds, diffuse redness, and duodenal ulcers were associated with a high titer. Regular arrangements of collecting venules, fundic gland polyps, superficial gastritis, and gastroesophageal reflux disease were related to a low titer. Multivariate analysis revealed that nodularity (P = 0.0094), atrophy (P = 0.0076), and age 40-59 years (vs age ≥ 60 years, P = 0.0090) were correlated with a high serum antibody titer in H. pylori-infected patients. Intestinal metaplasia and atrophy were related to age ≥ 60 years in group C and D. CONCLUSION: Serum antibody titer changes with age, reflects gastric mucosal inflammation, and is useful in predicting the risk of gastric cancer.

DOI： 10.3748/wjg.v24.i35.4061

Risk Factors for Viral Infections in Pediatric Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Narita Atsushi, Ito Yoshinori, Torii Yuka, Kawada Jun-Ichi, Miwata Shunsuke, Narita Kotaro, Kitazawa Hironobu, Hamada Motoharu, Kataoka Shinsuke, Ichikawa Daisuke, Ito Rieko, Murakami Norihiro, Kojima Daiei, Suzuki Kyogo, Nishikawa Eri, Kawashima Nozomu, Okuno Yusuke, Muramatsu Hideki, Hama Asahito, Kojima Seiji, Takahashi Yoshiyuki

BONE MARROW TRANSPLANTATION Vol. 53 page： 588-589 2018.9

Integration Mapping of piggyBac-Mediated CD19 Chimeric Antigen Receptor T Cells Analyzed by Novel Tagmentation-Assisted PCR. Reviewed International journal Open Access

Motoharu Hamada, Nobuhiro Nishio, Yusuke Okuno, Satoshi Suzuki, Nozomu Kawashima, Hideki Muramatsu, Shoma Tsubota, Matthew H Wilson, Daisuke Morita, Shinsuke Kataoka, Daisuke Ichikawa, Norihiro Murakami, Rieko Taniguchi, Kyogo Suzuki, Daiei Kojima, Yuko Sekiya, Eri Nishikawa, Atsushi Narita, Asahito Hama, Seiji Kojima, Yozo Nakazawa, Yoshiyuki Takahashi

EBioMedicine Vol. 34 page： 18 - 26 2018.8

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

Insertional mutagenesis is an important risk with all genetically modified cell therapies, including chimeric antigen receptor (CAR)-T cell therapy used for hematological malignancies. Here we describe a new tagmentation-assisted PCR (tag-PCR) system that can determine the integration sites of transgenes without using restriction enzyme digestion (which can potentially bias the detection) and allows library preparation in fewer steps than with other methods. Using this system, we compared the integration sites of CD19-specific CAR genes in final T cell products generated by retrovirus-based and lentivirus-based gene transfer and by the piggyBac transposon system. The piggyBac system demonstrated lower preference than the retroviral system for integration near transcriptional start sites and CpG islands and higher preference than the lentiviral system for integration into genomic safe harbors. Integration into or near proto-oncogenes was similar in all three systems. Tag-PCR mapping is a useful technique for assessing the risk of insertional mutagenesis.

DOI： 10.1016/j.ebiom.2018.07.008

Late-phase human herpesvirus 6B reactivation in hematopoietic stem cell transplant recipients. Reviewed International journal

Hiroki Miura, Yoshiki Kawamura, Fumihiko Hattori, Makito Tanaka, Kazuko Kudo, Masaru Ihira, Hiroshi Yatsuya, Yoshiyuki Takahashi, Seiji Kojima, Tetsushi Yoshikawa

Transplant infectious disease : an official journal of the Transplantation Society Vol. 20 ( 4 ) page： e12916 2018.8

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

BACKGROUND: We sought to determine whether late-phase human herpesvirus 6B (HHV-6B) infection in hematopoietic stem cell transplant (HSCT) recipients was associated with serious outcomes and mortality. METHODS: The occurrence and course of HHV-6B infection was monitored for at least 60 days after transplant using virus isolation and real-time polymerase chain reaction. Risk factors for late-phase HHV-6B infection were examined, and the propensity score was calculated with significant risk factors. The inverse probability-weighted multivariable logistic regression analysis was performed to estimate odds ratios (ORs) and the 95% confidence intervals (95% CI) for mortality. RESULTS: Late-phase HHV-6B infection was observed in 12/89 (13.5%) of the HSCT recipients. Older age (OR: 10.3, 95% CI: 2.1/72.9, P = .0027), hematologic malignancy (OR: 10.3, 95% CI: 1.8/97.1, P = .0063), unrelated donor transplantation (OR: 5.3, 95% CI: 1.1/36.0, P = .0345), and sex-mismatched donor transplantation (OR: 6.3, 95% CI: 1.4/39.5, P = .0149) were identified as risk factors for late-phase HHV-6B infection. Fifteen subjects died (17%). Inverse probability-weighted multivariable logistic model analysis revealed that late-phase HHV-6B infection was an independent risk factor for mortality (OR: 4.2, 95% CI: 1.7/11.0, P = .0012). Among 5 of the fatal cases of late-phase HHV-6B infection, viral infection might be associated with severe clinical manifestations. CONCLUSION: Late-phase HHV-6B infection in HSCT recipients was associated with worse outcomes. The full spectrum of clinical features of the infection has not been fully elucidated, and therefore, recipients with high-risk factors for late-phase HHV-6B infection should be carefully monitored.

DOI： 10.1111/tid.12916

Expression and localization of aquaporins 3 and 7 in bull spermatozoa and their relevance to sperm motility after cryopreservation. Reviewed Open Access

Fujii T, Hirayama H, Fukuda S, Kageyama S, Naito A, Yoshino H, Moriyasu S, Yamazaki T, Sakamoto K, Hayakawa H, Takahashi K, Takahashi Y, Sawai K

The Journal of reproduction and development Vol. 64 ( 4 ) page： 327 - 335 2018.8

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

Artificial insemination with cryopreserved semen is a well-developed technique commonly used for controlled reproduction in cattle. However, despite current technical advances, cryopreservation continues to damage bull spermatozoa, resulting in a loss of approximately 30 to 50% of viable spermatozoa post thawing. To further improve the efficiency of cryopreservation of bull spermatozoa, understanding the molecular mechanisms underlying the cryobiological properties that affect cryoinjuries during cryopreservation process of bull spermatozoa is required. In this study, we examined the expression and localization of aquaporin (AQP) 3 and AQP7 in fresh, cooled, and frozen-thawed bull spermatozoa. Furthermore, we investigated the relevance of AQP3 and AQP7 to motility and to membrane integrity in frozen-thawed bull spermatozoa. Western blotting against AQP3 and AQP7 in bull spermatozoa revealed bands with molecular weights of approximately 42 kDa and 53 kDa, respectively. In immunocytochemistry analyses, immunostaining of AQP3 was clearly observed in the principal piece of the sperm tail. Two immunostaining patterns were observed for AQP7 -pattern 1: diffuse staining in head and entire tail, and pattern 2: diffuse staining in head and clear staining in mid-piece. Cooling and freeze-thawing did not affect the localization pattern of AQP7 and the relative abundances of AQP3 and AQP7 evaluated by Western blotting. Furthermore, we demonstrated that the relative abundances of AQP3 and AQP7 varied among ejaculates, and they were positively related to sperm motility, particularly sperm velocity, post freeze-thawing. Our findings suggest that AQP3 and AQP7 are possibly involved in the tolerance to freeze-thawing in bull spermatozoa, particularly in the sperm's tail.

DOI： 10.1262/jrd.2017-166

Diagnostic performance of 18F-FDG PET/CT and whole-body diffusion-weighted imaging with background body suppression (DWIBS) in detection of lymph node and bone metastases from pediatric neuroblastoma. Reviewed Open Access

小児循環器疾患の基礎研究から臨床への応用家族性大動脈弁上狭窄において、遺伝子内微小欠失の頻度は高い次世代シーケンサーによる7家系の解析と臨床応用への可能性

早野聡, 奥野友介, 堤真紀子, 稲垣秀人, 深澤佳絵, 倉橋浩樹, 小島勢二, 高橋義行, 加藤太一

日本小児循環器学会雑誌 Vol. 34 ( Suppl.1 ) page： s1 - 122 2018.7

冠動脈病変合併リスクの高い川崎病患者に対する投与期間を短縮した免疫グロブリン・プレドニゾロン初期併用療法多施設共同ランダム化比較試験による検証

加藤太一, 深澤佳絵, 山本英範, 沼口敦, 早野聡, 岸本泰明, 長井典子, 安藤昌彦, 高橋義行

日本小児循環器学会雑誌 Vol. 34 ( Suppl.1 ) page： s1 - 283 2018.7

Hiroaki Ishiguchi, Shinji Ito, Katsuhiko Kato, Yusuke Sakurai, Hisashi Kawai, Naotoshi Fujita, Shinji Abe, Atsushi Narita, Nobuhiro Nishio, Hideki Muramatsu, Yoshiyuki Takahashi, Shinji Naganawa

Annals of nuclear medicine Vol. 32 ( 5 ) page： 348 - 362 2018.6

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

OBJECTIVE: Recent many studies have shown that whole body "diffusion-weighted imaging with background body signal suppression" (DWIBS) seems a beneficial tool having higher tumor detection sensitivity without ionizing radiation exposure for pediatric tumors. In this study, we evaluated the diagnostic performance of whole body DWIBS and 18F-FDG PET/CT for detecting lymph node and bone metastases in pediatric patients with neuroblastoma. METHODS: Subjects in this retrospective study comprised 13 consecutive pediatric patients with neuroblastoma (7 males, 6 females; mean age, 2.9 ± 2.0 years old) who underwent both 18F-FDG PET/CT and whole-body DWIBS. All patients were diagnosed as neuroblastoma on the basis of pathological findings. Eight regions of lymph nodes and 17 segments of skeletons in all patients were evaluated. The images of 123I-MIBG scintigraphy/SPECT-CT, bone scintigraphy/SPECT, and CT were used to confirm the presence of lymph node and bone metastases. Two radiologists trained in nuclear medicine evaluated independently the uptake of lesions in 18F-FDG PET/CT and the signal-intensity of lesions in whole-body DWIBS visually. Interobserver difference was overcome through discussion to reach a consensus. The sensitivities, specificities, and overall accuracies of 18F-FDG PET/CT and whole-body DWIBS were compared using McNemer's test. Positive predictive values (PPVs) and negative predictive values (NPVs) of both modalities were compared using Fisher's exact test. RESULTS: The total numbers of lymph node regions and bone segments which were confirmed to have metastasis in the total 13 patients were 19 and 75, respectively. The sensitivity, specificity, overall accuracy, PPV, and NPV of 18F-FDG PET/CT for detecting lymph node metastasis from pediatric neuroblastoma were 100, 98.7, 98.9, 95.0, and 100%, respectively, and those for detecting bone metastasis were 90.7, 73.1, 80.3, 70.1, and 91.9%, respectively. In contrast, the sensitivity, specificity, overall accuracy, PPV, and NPV of whole-body DWIBS for detecting bone metastasis from pediatric neuroblastoma were 94.7, 24.0, 53.0, 46.4 and 86.7%, respectively, whereas those for detecting lymph node metastasis were 94.7, 85.3, 87.2, 62.1, and 98.5%, respectively. The low specificity, overall accuracy, and PPV of whole-body DWIBS for detecting bone metastasis were due to a high incidence of false-positive findings (82/108, 75.9%). The specificity, overall accuracy, and PPV of whole-body DWIBS for detecting lymph node metastasis were also significantly lower than those of 18F-FDG PET/CT for detecting lymph node metastasis, although the difference between these 2 modalities was less than that for detecting bone metastasis. CONCLUSION: The specificity, overall accuracy, and PPV of whole-body DWIBS are significantly lower than those of 18F-FDG PET/CT because of a high incidence of false-positive findings particularly for detecting bone metastasis, whereas whole-body DWIBS shows a similar level of sensitivities for detecting lymph node and bone metastases to those of 18F-FDG PET/CT. DWIBS should be carefully used for cancer staging in children because of its high incidence of false-positive findings in skeletons.

DOI： 10.1007/s12149-018-1254-z

Integrated molecular profiling of juvenile myelomonocytic leukemia. Reviewed International journal Open Access

Norihiro Murakami, Yusuke Okuno, Kenichi Yoshida, Yuichi Shiraishi, Genta Nagae, Kyogo Suzuki, Atsushi Narita, Hirotoshi Sakaguchi, Nozomu Kawashima, Xinan Wang, Yinyan Xu, Kenichi Chiba, Hiroko Tanaka, Asahito Hama, Masashi Sanada, Masafumi Ito, Masashi Hirayama, Arata Watanabe, Toshihide Ueno, Seiji Kojima, Hiroyuki Aburatani, Hiroyuki Mano, Satoru Miyano, Seishi Ogawa, Yoshiyuki Takahashi, Hideki Muramatsu

Blood Vol. 131 ( 14 ) page： 1576 - 1586 2018.4

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

Juvenile myelomonocytic leukemia (JMML), a rare and aggressive myelodysplastic/myeloproliferative neoplasm that occurs in infants and during early childhood, is characterized by excessive myelomonocytic cell proliferation. More than 80% of patients harbor germ line and somatic mutations in RAS pathway genes (eg, PTPN11, NF1, NRAS, KRAS, and CBL), and previous studies have identified several biomarkers associated with poor prognosis. However, the molecular pathogenesis of 10% to 20% of patients and the relationships among these biomarkers have not been well defined. To address these issues, we performed an integrated molecular analysis of samples from 150 JMML patients. RNA-sequencing identified ALK/ROS1 tyrosine kinase fusions (DCTN1-ALK, RANBP2-ALK, and TBL1XR1-ROS1) in 3 of 16 patients (18%) who lacked canonical RAS pathway mutations. Crizotinib, an ALK/ROS1 inhibitor, markedly suppressed ALK/ROS1 fusion-positive JMML cell proliferation in vitro. Therefore, we administered crizotinib to a chemotherapy-resistant patient with the RANBP2-ALK fusion who subsequently achieved complete molecular remission. In addition, crizotinib also suppressed proliferation of JMML cells with canonical RAS pathway mutations. Genome-wide methylation analysis identified a hypermethylation profile resembling that of acute myeloid leukemia (AML), which correlated significantly with genetic markers with poor outcomes such as PTPN11/NF1 gene mutations, 2 or more genetic mutations, an AML-type expression profile, and LIN28B expression. In summary, we identified recurrent activated ALK/ROS1 fusions in JMML patients without canonical RAS pathway gene mutations and revealed the relationships among biomarkers for JMML. Crizotinib is a promising candidate drug for the treatment of JMML, particularly in patients with ALK/ROS1 fusions.

DOI： 10.1182/blood-2017-07-798157

Phase I study of cord blood transplantation with intrabone marrow injection of mesenchymal stem cells: A clinical study protocol. Reviewed International journal Open Access

Tatsunori Goto, Makoto Murata, Seitaro Terakura, Tetsuya Nishida, Yoshiya Adachi, Yoko Ushijima, Kazuyuki Shimada, Yuichi Ishikawa, Fumihiko Hayakawa, Nobuhiro Nishio, Satoshi Nishiwaki, Akihiro Hirakawa, Katsuyoshi Kato, Yoshiyuki Takahashi, Hitoshi Kiyoi

Medicine Vol. 97 ( 17 ) page： e0449 2018.4

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

INTRODUCTION: Delayed hematological recovery, graft failure, and acute graft-versus-host disease (GVHD) still remain major problems in cord blood transplantation (CBT). Mesenchymal stem cells (MSCs) are known to support bone marrow stroma and promote hematopoiesis. Additionally, MSCs possess immunomodulatory properties and are used clinically for the treatment of acute GVHD. Therefore, the use of MSCs to enhance engraftment and prevent GVHD after allogeneic hematopoietic cell transplantation has been explored. Recent clinical trials have shown the feasibility and safety of intravenous cotransplantation of MSCs with cord blood cells in pediatric patients, but not in adult patients, who are at greater risk of graft failure. As for the route of administration of MSCs, direct intrabone marrow injection of MSCs is thought to enhance the engraftment of cord blood cells more than intravenous injection. Based on these background findings, this clinical trial was designed to develop a new strategy to enhance engraftment and prevent GVHD after CBT. METHODS AND ANALYSIS: This is a single-center, phase I, clinical study to evaluate the safety of CBT combined with intrabone marrow injection of ex vivo expanded MSCs from bone marrow of a third-party donor. Adult patients with hematological disorders are eligible for this study. The target sample size is 5, and the registration period is 3 years. The target dose of MSCs infused is 0.5 × 10 cells/kg of patient body weight. On the day of CBT, MSCs are injected into the intrabone marrow of the patient 4 hours before the infusion of a single cord blood unit. The conditioning regimen varies according to patient age and disease. GVHD prophylaxis consists of a combination of tacrolimus and methotrexate. The primary endpoint of this study is infusional toxicity of MSCs within 14 days after transplantation.

DOI： 10.1097/MD.0000000000010449

Enhanced Expression of Anti-CD19 Chimeric Antigen Receptor in piggyBac Transposon-Engineered T Cells. Reviewed International journal Open Access

Daisuke Morita, Nobuhiro Nishio, Shoji Saito, Miyuki Tanaka, Nozomu Kawashima, Yusuke Okuno, Satoshi Suzuki, Kazuyuki Matsuda, Yasuhiro Maeda, Matthew H Wilson, Gianpietro Dotti, Cliona M Rooney, Yoshiyuki Takahashi, Yozo Nakazawa

Molecular therapy. Methods & clinical development Vol. 8 page： 131 - 140 2018.3

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

Adoptive T cell therapy using chimeric antigen receptor (CAR)-modified T cells is a promising cancer immunotherapy. We previously developed a non-viral method of gene transfer into T cells using a piggyBac transposon system to improve the cost-effectiveness of CAR-T cell therapy. Here, we have further improved our technology by a novel culture strategy to increase the transfection efficiency and to reduce the time of T cell manufacturing. Using a CH2CH3-free CD19-specific CAR transposon vector and combining irradiated activated T cells (ATCs) as feeder cells and virus-specific T cell receptor (TCR) stimulation, we achieved 51.4% ± 14% CAR+ T cells and 2.8-fold expansion after 14 culture days. Expanded CD19.CAR-T cells maintained a significant fraction of CD45RA+CCR7+ T cells and demonstrated potent antitumor activity against CD19+ leukemic cells both in vitro and in vivo. Therefore, piggyBac-based gene transfer may provide an alternative to viral gene transfer for CAR-T cell therapy.

DOI： 10.1016/j.omtm.2017.12.003

Comprehensive detection of pathogens in immunocompromised children with bloodstream infections by next-generation sequencing. Reviewed International journal Open Access

Kazuhiro Horiba, Jun-Ichi Kawada, Yusuke Okuno, Nobuyuki Tetsuka, Takako Suzuki, Shotaro Ando, Yasuko Kamiya, Yuka Torii, Tetsuya Yagi, Yoshiyuki Takahashi, Yoshinori Ito

Scientific reports Vol. 8 ( 1 ) page： 3784 - 3784 2018.2

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

Bloodstream infection (BSI) is a severe complication in immunocompromised patients. Next-generation sequencing (NGS) allows us to analyze comprehensively and quantitatively all microorganisms present in a clinical sample. Thirty-five pediatric patients (12 with BSI and 23 with suspected BSI/negative blood culture) were enrolled. Plasma/serum samples were used for sequencing and the results were compared with those from blood culture. Sequencing reads of bacteria isolated in blood culture were identified by NGS in all plasma/serum samples at disease onset. Bacteria isolated in blood culture were identical to the dominant bacteria by NGS in 8 of 12 patients. Bacterial reads per million reads of the sequence depth (BR) > 200 and relative importance values of the dominant bacteria (P1) > 0.5 were employed to determine causative pathogens. Causative pathogens were detected using these criteria in 7 of 12 patients with BSI. Additionally, causative bacteria were detected in the plasma/serum at 7 days before disease onset in two patients with catheter-related BSI. Causative pathogens, including virus, were identified in three patients with suspected BSI. Lastly, a total of 62 resistance genes were detected by NGS. In conclusion, NGS is a new method to identify causative microorganisms in BSI and may predict BSI in some patients.

DOI： 10.1038/s41598-018-22133-y

Comprehensive genetic analysis of donor cell derived leukemia with KMT2A rearrangement. Reviewed International journal

Rieko Taniguchi, Hideki Muramatsu, Yusuke Okuno, Kyogo Suzuki, Satoshi Obu, Masahiro Nakatochi, Teppei Shimamura, Yoshiyuki Takahashi, Yasuo Horikoshi, Kenichiro Watanabe, Seiji Kojima

Pediatric blood & cancer Vol. 65 ( 2 ) 2018.2

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

BACKGROUND: Donor cell leukemia (DCL) occurs after allogeneic hematopoietic stem cell transplantation. Several mechanisms, including occult leukemic/preleukemic subclones in the donor graft and germline predisposition to leukemia, are proposed to be associated with DCL's molecular pathogenesis. We report a comprehensive genetic analysis of a patient with KMT2A-rearranged DCL after allogeneic bone marrow transplantation for refractory cytopenia of childhood. PROCEDURE: We performed a whole-exome sequencing of the recipient's peripheral blood before transplant and the donor's peripheral blood and the recipient's bone marrow at the time of DCL diagnosis. RNA sequencing was also performed to detect fusion genes in DCL blasts. RESULTS: There were no germline mutations that were associated with a predisposition to leukemia in the recipient and donor. Furthermore, there were no detectable somatic alterations except KMT2A-MLLT10 and other related gene fusions in DCL. KMT2A-MLLT10 was not detectable in the donor's bone marrow. CONCLUSION: We propose a novel pattern of the molecular pathogenesis of DCL solely involving a genetic mutation acquired after transplant with no identifiable genetic factor related to the donor and recipient.

DOI： 10.1002/pbc.26823

[5. Evaluation of Pathology of Heart Disease Models Using Preclinical Ultra-high Field MRI]. Reviewed

Takahashi Y, Saito S

Nihon Hoshasen Gijutsu Gakkai zasshi Vol. 74 ( 4 ) page： 404 - 411 2018

Neurocan, an extracellular chondroitin sulfate proteoglycan, stimulates neuroblastoma cells to promote malignant phenotypes. Reviewed International journal Open Access

Zhendong Su, Satoshi Kishida, Shoma Tsubota, Kazuma Sakamoto, Dongliang Cao, Shinichi Kiyonari, Miki Ohira, Takehiko Kamijo, Atsushi Narita, Yinyan Xu, Yoshiyuki Takahashi, Kenji Kadomatsu

Oncotarget Vol. 8 ( 63 ) page： 106296 - 106310 2017.12

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

Neurocan (NCAN), a secreted chondroitin sulfate proteoglycan, is one of the major inhibitory molecules for axon regeneration in nervous injury. However, its role in cancer is not clear. Here we observed that high NCAN expression was closely associated with the unfavorable outcome of neuroblastoma (NB). NCAN was also highly and ubiquitously expressed in the early lesions and terminal tumor of TH-MYCN mice, a NB model. Interestingly, exogenous NCAN (i.e., overexpression, recombinant protein and conditioned medium) transformed adherent NB cells into spheres whose malignancies in vitro (anchorage-independent growth and chemoresistance) and in vivo (xenograft tumor growth) were potentiated. Both chondroitin sulfate sugar chains and NCAN's core protein were essential for the sphere formation. The CSG3 domain was essential in the moiety of NCAN. Our comprehensive microarray analysis and RT-qPCR of mRNA expression suggested that NCAN treatment promoted cell division, and urged cells to undifferentiated state. The knockdown of NCAN in tumor sphere cells cultured from TH-MYCN mice resulted in growth suppression in vitro and in vivo. Our findings suggest that NCAN, which stimulates NB cells to promote malignant phenotypes, is an extracellular molecule providing a growth advantage to cancer cells.

DOI： 10.18632/oncotarget.22435

Comprehensive detection of viruses in pediatric patients with acute liver failure using next-generation sequencing. Reviewed International journal

Takako Suzuki, Jun-Ichi Kawada, Yusuke Okuno, Satoshi Hayano, Kazuhiro Horiba, Yuka Torii, Yoshiyuki Takahashi, Syuichiro Umetsu, Tsuyoshi Sogo, Ayano Inui, Yoshinori Ito

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Vol. 96 page： 67 - 72 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

BACKGROUND: Pediatric acute liver failure (PALF) is a rare and severe syndrome that frequently requires liver transplantation. Viruses are one of the most frequent causes of this disease, however, pathogenic viruses are not determined in many patients. Recently next-generation sequencing (NGS) has been applied to comprehensively detect pathogens of infectious diseases of unknown etiology. OBJECTIVES: To evaluate an NGS-based approach for detecting pathogenic viruses in patients with PALF or acute hepatitis of unknown etiology. STUDY DESIGN: To detect virus-derived DNA and RNA sequences existing in sera/plasma from patients, both DNA and RNA sequencing were performed. First, we validated the ability of NGS to detect viral pathogens in clinical serum/plasma samples, and compared different commercial RNA library preparation methods Then, serum/plasma of fourteen patients with PALF or acute hepatitis of unknown etiology were evaluated using NGS. RESULTS: Among three RNA library preparation methods, Ovation RNA-Seq System V2 had the highest sensitivity to detect RNA viral sequences. Among fourteen patients, sequence reads of torque teno virus, adeno-associated virus, and stealth virus were found in the sera of one patient each, however, the pathophysiological role of these three viruses was not clarified. Significant virus reads were not detected in the remaining 11 patients. CONCLUSIONS: This finding might be due to low virus titer in blood at the time of referral or a non-infectious cause might be more frequent. These results suggest an NGS-based approach has potential to detect viral pathogens in clinical samples and would contribute to clarification of the etiology of PALF.

DOI： 10.1016/j.jcv.2017.10.001

Clinical Trial of CD19 CAR-T Cell Therapy with non-virus Vector System

Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 64 page： S3 - S3 2017.11

Bevacizumab, Irinotecan, and Temozolomide Combination as Salvage Chemotherapy for Relapsed Pediatric Brain Tumor

Shinsuke Kataoka, Hideki Muramatsu, Kotaro Narita, Motoharu Hamada, Norihiro Murakami, Rieko Tanigushi, Daisuke Ichikawa, Hironori Kitazawa, Daiei Kojima, Kyogo Suzuki, Nozomu Kawashima, Eri Nishikawa, Atsushi Narita, Yusuke Okuno, Nobuhiro Nishio, Asahito Hama, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 64 page： S55 - S55 2017.11

Clinical Prognostic Factors in Patients with High-risk Neuroblastoma Undergoing A Single Autologous Stem Cell Transplant

Yuya Saito, Chikako Kiyotani, Masami Inoue, Yoshiyuki Takahashi, Atsushi Ogawa, Motoaki Chin, Yuuki Koga, Koji Kato, Katsuyoshi Koh, Kenichiro Watanabe, Yoshiko Hashii, Atsushi Sato, Yuko Atsuta, Kimikazu Matsumoto

PEDIATRIC BLOOD & CANCER Vol. 64 page： S42 - S42 2017.11

Human Herpesvirus 6B Infection in Pediatric Hematopoietic Stem Cell Transplantation

Hiroki Miura, Kazuko Kudo, Makito Tanaka, Yoshiyuki Takahashi, Seji Kojima, Koji Kato, Nao Yoshida, Hirotoshi Sakaguchi, Tetsushi Yoshikawa

PEDIATRIC BLOOD & CANCER Vol. 64 page： S76 - S76 2017.11

Killer Cell Immunoglobulin-like Receptor Ligand-mismatched Allogeneic Cord Blood Transplantation Reduces Relapse and Improves Survival in Children with Refractory Neuroblastoma

Nobuhiro Nishio, Shinnsuke Kataoka, Motoharu Hamada, Daisuke Ichikawa, Rieko Taniguchi, Norihiro Murakami, Daiei Kojima, Kyogo Suzuki, Nozomu Kawasima, Eri Nishikawa, Yusuke Okuno, Atsushi Narita, Hideki Muramatsu, Asahito Hama, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 64 page： S23 - S24 2017.11

Integrated Molecular Profiling of Juvenile Myelomonocytic Leukemia

Norihiro Murakami, Hideki Muramatsu, Yusuke Okuno, Kenichi Yoshida, Yuichi Shiraishi, Genta Nagae, Kyogo Suzuki, Atsushi Narita, Hirotoshi Sakaguchi, Nozomu Kawashima, Xinan Wang, Yinyan Xu, Kenichi Chiba, Hiroko Tanaka, Nobuhiro Nishio, Asahito Hama, Masashi Sanada, Masashi Hirayama, Arata Watanabe, Toshihide Ueno, Seiji Kojima, Hiroyuki Aburatani, Hiroyuki Mano, Satoru Miyano, Seishi Ogawa, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 64 page： S19 - S20 2017.11

Identification of FLVCR1 as a Novel Causative Gene of Inherited Ineffective Erythropoiesis in Humans

Nozomu Kawashima, Yusuke Okuno, Mitsutaka Shiota, Hideki Muramatsu, Kenichi Yoshida, Masahito Ikawa, Asahito Hama, Masafumi Ito, Sayoko Doisaki, Norihiro Murakami, Kyogo Suzuki, Atsushi Narita, Nobuhiro Nishio, Yoshiyuki Takahashi, Seishi Ogawa, Seiji Kojima

PEDIATRIC BLOOD & CANCER Vol. 64 page： S20 - S20 2017.11

Correlation of Bone Marrow Morphology with Clinical Findings and Gene Alterations in Patients with Diamond-Blackfan Anemia

Asahito Hama, Tsutomu Toki, Akie Kobayashi, Hideki Muramatsu, Yusuke Okuno, Daisuke Hasegawa, Kazue Nozawa, Yoshiyuki Takahashi, Kenichiro Watanabe, Atsushi Manabe, Masafumi Ito, Etsuro Ito, Seiji Kojima

PEDIATRIC BLOOD & CANCER Vol. 64 page： S28 - S28 2017.11

Germline Mutation in Pediatric Patients with Aplastic Anemia

Atsushi Narita, Hideki Muramatsu, Yusuke Okuno, Xinan Wang, Yinyan Xu, Nozomu Kawashima, Nobuhiro Nishio, Asahito Hama, Hirotoshi Sakaguchi, Nao Yoshida, Koji Kato, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 64 page： S28 - S29 2017.11

Vorinostat and Bortezomib Combined Intensive Chemotherapy for Children with KMT2A (MLL)-rearranged Acute Lymphoblastic Leukemia

Suzuki, K; Muramatsu, H; Okuno, Y; Narita, K; Kitazawa, H; Huang, Y; Ichikawa, D; Kataoka, S; Hamada, M; Murakami, N; Taniguchi, R; Kojima, D; Sekiya, Y; Nishikawa, E; Kawashima, N; Narita, A; Nishio, N; Hama, A; Kojima, S; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 64 page： S90 - S90 2017.11

Newborn Screening for Severe Combined Immunodeficiency in Aichi Prefecture

Daiei Kojima, Hideki Muramatsu, Yusuke Okuno, Kotaro Narita, Norihiro Murakami, Daisuke Ichikawa, Motoharu Hamada, Shinsuke Kataoka, Hironobu Kitazawa, Rieko Taniguchi, Kyogo Suzuki, Nozomu Kawashima, Eri Nishikawa, Atsushi Narita, Nobuhiro Nishio, Asahito Hama, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 64 page： S33 - S33 2017.11

Retrospective Analysis of High Risk Childhood AML Undergoing Allo-SCT in First CR: Results of AML-05 by JPLSG

PEDIATRIC BLOOD & CANCER Vol. 64 page： S68 - S68 2017.11

Treatment Outcomes and Prognostic Factors after Allogeneic-HSCT for Patients with Low and Intermediate Risk in JPLSG AML-05 study

Yoshiko Hashii, Nobuyuki Hyakuna, Hiroyuki Ishida, Katsutsugu Umeda, Yoshiyuki Takahashi, Masayuki Nagasawa, Hiromasa Yabe, Yozo Nakazawa, Hiroyuki Fujisaki, Michihiro Yano, Kimikazu Matsumoto, Hiroaki Goto, Harumi Kakuda, Katsuyoshi Koh, Daisuke Tomizawa, Akio Tawa, Takashi Taga, Souichi Adachi, Koji Kato

PEDIATRIC BLOOD & CANCER Vol. 64 page： S19 - S19 2017.11

Successful Allogeneic Cord Blood Transplantation in three Children with Aplastic Anemia Pretreated with Flu plus Mel plus TBI

Eri Nishikawa, Hironobu Kitazawa, Koutarou Narita, Motoharu Hamada, Shinsuke Kataoka, Norihiro Murakami, Daisuke Ichikawa, Daiei Kojima, Kyogo Suzuki, Rieko Taniguchi, Nozomu Kawashima, Atsushi Narita, Yusuke Okuno, Hideki Muramatsu, Nobuhiro Nishio, Asahito Hama, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 64 page： S75 - S76 2017.11

Vorinostat and Bortezomib Combined Intensive Chemotherapy for Children with KMT2A (MLL)-rearranged Acute Lymphoblastic Leukemia

Suzuki Kyogo, Muramatsu Hideki, Okuno Yusuke, Narita Kotaro, Kitazawa Hironobu, Huang Yue, Ichikawa Daisuke, Kataoka Shinsuke, Hamada Motoharu, Murakami Norihiro, Taniguchi Rieko, Kojima Daiei, Sekiya Yuko, Nishikawa Eri, Kawashima Nozomu, Narita Atsushi, Nishio Nobuhiro, Hama Asahito, Kojima Seiji, Takahashi Yoshiyuki

PEDIATRIC BLOOD & CANCER Vol. 64 page： S90-S90 2017.11

難治性進行神経芽腫に対するKIRリガンド不一致同種臍帯血移植による再発抑制効果と生存率の向上(Killer cell immunoglobulin-like receptor ligand-mismatched allogeneic cord blood transplantation reduces relapse and improves survival in children with refractory neuroblastoma)

Nishio Nobuhiro, Kataoka Shinsuke, Hamada Motoharu, Ichikawa Daisuke, Taniguchi Rieko, Murakami Norihiro, Kojima Daiei, Suzuki Kyogo, Kawashima Nozomu, Nishikawa Eri, Okuno Yusuke, Narita Atsushi, Muramatsu Hideki, Hama Asahito, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 54 ( 4 ) page： 227 - 227 2017.10

若年性骨髄単球性白血病に対する包括的遺伝子解析(Integrated molecular profiling of juvenile myelomonocytic leukemia)

Murakami Norihiro, Muramatsu Hideki, Okuno Yusuke, Yoshida Kenichi, Shiraishi Yuichi, Nagae Genta, Suzuki Kyogo, Narita Atsushi, Sakaguchi Hirotoshi, Kawashima Nozomu, Wang Xinan, Xu Yinyan, Chiba Kenichi, Tanaka Hiroko, Nishio Nobuhiro, Hama Asahito, Sanada Masashi, Hirayama Masashi, Watanabe Arata, Ueno Toshihide, Kojima Seiji, Aburatani Hiroyuki, Mano Hiroyuki, Miyano Satoru, Ogawa Seishi, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 54 ( 4 ) page： 224 - 224 2017.10

愛知県における重症複合免疫不全症に対する新生児マススクリーニング(Newborn screening for severe combined immunodeficiency in Aichi Prefecture)

Kojima Daiei, Muramatsu Hideki, Okuno Yusuke, Narita Kotaro, Murakami Norihiro, Ichikawa Daisuke, Hamada Motoharu, Kataoka Shinsuke, Kitazawa Hironobu, Taniguchi Rieko, Suzuki Kyogo, Kawashima Nozomu, Nishikawa Eri, Narita Atsushi, Nishio Nobuhiro, Hama Asahito, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 54 ( 4 ) page： 238 - 238 2017.10

小児再生不良性貧血における胚細胞変異(Germline mutation in pediatric patients with aplastic anemia)

Narita Atsushi, Muramatsu Hideki, Okuno Yusuke, Wang Xinan, Xu Yinyan, Kawashima Nozomu, Nishio Nobuhiro, Hama Asahito, Sakaguchi Hirotoshi, Yoshida Nao, Kato Koji, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 54 ( 4 ) page： 233 - 233 2017.10

ヒト遺伝性無効造血の原因となる新規FLVCR1遺伝子変異の同定(Identification of FLVCR1 as a novel causative gene of inherited ineffective erythropoiesis in humans)

Kawashima Nozomu, Okuno Yusuke, Shiota Mitsutaka, Muramatsu Hideki, Yoshida Kenichi, Ikawa Masahito, Hama Asahito, Ito Masafumi, Doisaki Sayoko, Murakami Norihiro, Suzuki Kyogo, Narita Atsushi, Nishio Nobuhiro, Takahashi Yoshiyuki, Ogawa Seishi, Kojima Seiji

日本小児血液・がん学会雑誌 Vol. 54 ( 4 ) page： 224 - 224 2017.10

再発小児脳腫瘍に対するベバシズマブ・イリノテカン・テモゾロミド併用救援化学療法(Bevacizumab, Irinotecan, and Temozolomide combination as salvage chemotherapy for relapsed pediatric brain tumor)

Kataoka Shinsuke, Muramatsu Hideki, Narita Kotaro, Hamada Motoharu, Murakami Norihiro, Tanigushi Rieko, Ichikawa Daisuke, Kitazawa Hironori, Kojima Daiei, Suzuki Kyogo, Kawashima Nozomu, Nishikawa Eri, Narita Atsushi, Okuno Yusuke, Nishio Nobuhiro, Hama Asahito, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 54 ( 4 ) page： 256 - 256 2017.10

KMT2A(MLL)遺伝子再構成陽性急性リンパ性白血病に対するボリノスタット・ボルテゾミブ併用化学療法(Vorinostat and bortezomib combined intensive chemotherapy for children with KMT2A(MLL)-rearranged acute lymphoblastic leukemia)

日本小児血液・がん学会雑誌 Vol. 54 ( 4 ) page： 287 - 287 2017.10

Flu+Mel+TBI前処置で同種臍帯血移植を施行した小児再生不良性貧血の3例(Successful allogeneic cord blood transplantation in three children with aplastic anemia pretreated with Flu+Mel+TBI)

Nishikawa Eri, Kitazawa Hironobu, Narita Kotaro, Hamada Motoharu, Kataoka Shinsuke, Murakami Norihiro, Ichikawa Daisuke, Kojima Daiei, Suzuki Kyogo, Taniguchi Rieko, Kawashima Nozomu, Narita Atsushi, Okuno Yusuke, Muramatsu Hideki, Nishio Nobuhiro, Hama Asahito, Kojima Seiji, Takahashi Yoshiyuki

日本小児血液・がん学会雑誌 Vol. 54 ( 4 ) page： 274 - 274 2017.10

Development of clinical paroxysmal nocturnal haemoglobinuria in children with aplastic anaemia. Reviewed International journal Open Access

Atsushi Narita, Hideki Muramatsu, Yusuke Okuno, Yuko Sekiya, Kyogo Suzuki, Motoharu Hamada, Shinsuke Kataoka, Daisuke Ichikawa, Rieko Taniguchi, Norihiro Murakami, Daiei Kojima, Eri Nishikawa, Nozomu Kawashima, Nobuhiro Nishio, Asahito Hama, Yoshiyuki Takahashi, Seiji Kojima

British journal of haematology Vol. 178 ( 6 ) page： 954 - 958 2017.9

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

The clinical significance of paroxysmal nocturnal haemoglobinuria (PNH) in children with aplastic anaemia (AA) remains unclear. We retrospectively studied 57 children with AA between 1992 and 2010. During the follow-up, five patients developed clinical PNH, in whom somatic PIGA mutations were detected by targeted sequencing. The 10-year probability of clinical PNH development was 10·2% (95% confidence interval, 3·6-20·7%). Furthermore, the detection of minor PNH clones by flow cytometry at AA diagnosis was a risk factor for the subsequent development of clinical PNH. These patients with PNH clones at AA diagnosis should undergo periodic monitoring for potential clinical PNH development.

DOI： 10.1111/bjh.14790

若年性骨髄単球性白血病に対する包括的遺伝子解析(Integrated molecular profiling of juvenile myelomonocytic leukemia)

Murakami Norihiro, Okuno Yusuke, Yoshida Kenichi, Shiraishi Yuichi, Nagae Genta, Suzuki Kyogo, Narita Atsushi, Sakaguchi Hirotoshi, Kawashima Nozomu, Wang Xinan, Xu Yinyan, Chiba Kenichi, Tanaka Hiroko, Hama Asahito, Sanada Masashi, Hirayama Masashi, Watanabe Arata, Ueno Toshihide, Kojima Seiji, Aburatani Hiroyuki, Mano Hiroyuki, Miyano Satoru, Ogawa Seishi, Takahashi Yoshiyuki, Muramatsu Hideki

臨床血液 Vol. 58 ( 9 ) page： 1457 - 1457 2017.9

先天性および後天性造血不全375例に対するクリニカルシーケンス(Clinical sequencing of 375 patients with inherited and acquired bone marrow failure syndromes)

Muramatsu Hideki, Okuno Yusuke, Yoshida Kenichi, Shiraishi Yuichi, Narita Atsushi, Sakaguchi Hirotoshi, Kawashima Nozomu, Xu Yinyan, Chiba Kenichi, Tanaka Hiroko, Hama Asahito, Sanada Masashi, Takahashi Yoshiyuki, Kanno Hitoshi, Yamaguchi Hiroki, Ohga Shouichi, Manabe Atsushi, Harigae Hideo, Kunishima Shinji, Ishii Eiichi, Kobayashi Masao, Koike Kenichi, Watanabe Kenichiro, Ito Etsuro, Takata Minoru, Yabe Miharu, Miyano Satoru, Ogawa Seishi, Kojima Seiji

臨床血液 Vol. 58 ( 9 ) page： 1519 - 1519 2017.9

Comparison of sperm subpopulation structures in first and second ejaculated semen from Japanese black bulls by a cluster analysis of sperm motility evaluated by a CASA system Reviewed Open Access

Chihiro Kanno, Kentaro Q. Sakamoto, Yojiro Yanagawa, Yoshiyuki Takahashi, Seiji Katagiri, Masashi Nagano

JOURNAL OF VETERINARY MEDICAL SCIENCE Vol. 79 ( 8 ) page： 1359 - 1365 2017.8

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC VET SCI

In the present study, bull sperm in the first and second ejaculates were divided into subpopulations based on their motility characteristics using a cluster analysis of data from computer-assisted sperm motility analysis (CASA). Semen samples were collected from 4 Japanese black bulls. Data from 9,228 motile sperm were classified into 4 clusters; 1) very rapid and progressively motile sperm, 2) rapid and circularly motile sperm with widely moving heads, 3) moderately motile sperm with heads moving frequently in a short length, and 4) poorly motile sperm. The percentage of cluster 1 varied between bulls. The first ejaculates had a higher proportion of cluster 2 and lower proportion of cluster 3 than the second ejaculates.

DOI： 10.1292/jvms.17-0012

Bone marrow transplantation for children with acquired bone marrow failure

Hama A., Manabe A., Hasegawa D., Nozawa K., Suzuki K., Narita A., Muramatsu H., Takahashi Y., Watanabe K., Ohara A., Ito M., Kojima S.

BONE MARROW TRANSPLANTATION Vol. 52 page： S414 - S414 2017.7

Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. Reviewed International journal Open Access

Hideki Muramatsu, Yusuke Okuno, Kenichi Yoshida, Yuichi Shiraishi, Sayoko Doisaki, Atsushi Narita, Hirotoshi Sakaguchi, Nozomu Kawashima, Xinan Wang, Yinyan Xu, Kenichi Chiba, Hiroko Tanaka, Asahito Hama, Masashi Sanada, Yoshiyuki Takahashi, Hitoshi Kanno, Hiroki Yamaguchi, Shouichi Ohga, Atsushi Manabe, Hideo Harigae, Shinji Kunishima, Eiichi Ishii, Masao Kobayashi, Kenichi Koike, Kenichiro Watanabe, Etsuro Ito, Minoru Takata, Miharu Yabe, Seishi Ogawa, Satoru Miyano, Seiji Kojima

Genetics in medicine : official journal of the American College of Medical Genetics Vol. 19 ( 7 ) page： 796 - 802 2017.7

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

PURPOSE: Precise genetic diagnosis of inherited bone marrow failure syndromes (IBMFS), a heterogeneous group of genetic disorders, is challenging but essential for precise clinical decision making. METHODS: We analyzed 121 IBMFS patients using a targeted sequencing covering 184 associated genes and 250 IBMFS patients using whole-exome sequencing (WES). RESULTS: We achieved successful genetic diagnoses for 53 of 121 patients (44%) using targeted sequencing and for 68 of 250 patients (27%) using WES. In the majority of cases (targeted sequencing: 45/53, 85%; WES: 63/68, 93%), the detected variants were concordant with, and therefore supported, the clinical diagnoses. However, in the remaining 13 cases (8 patients by target sequencing and 5 patients by WES), the clinical diagnoses were incompatible with the detected variants. CONCLUSION: Our approach utilizing targeted sequencing and WES achieved satisfactory diagnostic rates and supported the efficacy of massive parallel sequencing as a diagnostic tool for IBMFS.Genet Med advance online publication 19 January 2017.

DOI： 10.1038/gim.2016.197

PiggyBac transposon, a non-viral gene transfer system, mediated T cells expressing CD19 chimeric antigen receptor for a 'first in human' clinical trial

Takahashi, Y; Nishio, N; Hamada, M; Tanaka, M; Morita, D; Kawashima, N; Okuno, Y; Narita, A; Muramatsu, H; Hama, A; Kojima, S; Dotti, G; Nakazawa, Y

BONE MARROW TRANSPLANTATION Vol. 52 page： S161 - S162 2017.7

Recurrent MYB rearrangement in blastic plasmacytoid dendritic cell neoplasm

K Suzuki, Y Suzuki, A Hama, H Muramatsu, M Nakatochi, M Gunji, D Ichikawa, M Hamada, R Taniguchi, S Kataoka, N Murakami, D Kojima, Y Sekiya, E Nishikawa, N Kawashima, A Narita, N Nishio, Y Nakazawa, H Iwafuchi, K-i Watanabe, Y Takahashi, M Ito, S Kojima, S Kato, Y Okuno

Leukemia Vol. 31 ( 7 ) page： 1629 - 1633 2017.7

肺高血圧症(PH)をきたしtadalafilで治療した造血幹細胞移植(HSCT)後の3例

深澤佳絵, 早野聡, 沼口敦, 高橋義行, 加藤太一

日本小児循環器学会雑誌 Vol. 33 ( Suppl.1 ) page： s1 - 402 2017.7

PiggyBac transposon, a non-viral gene transfer system, mediated T cells expressing CD19 chimeric antigen receptor for a 'first in human' clinical trial

Takahashi Y, Nishio N, Hamada M, Tanaka M, Morita D, Kawashima N, Okuno Y, Narita A, Muramatsu H, Hama A, Kojima S, Dotti G, Nakazawa Y

BONE MARROW TRANSPLANTATION Vol. 52 page： S161-S162 2017.7

RECURRENT MYB REARRANGEMENT IN BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM

K. Suzuki, Y. Okuno, Y. Suzuki, A. Hama, H. Muramatsu, M. Nakatochi, M. Gunji, D. Ichikawa, M. Hamada, R. Taniguchi, S. Kataoka, N. Murakami, D. Kojima, Y. Sekiya, E. Nishikawa, N. Kawashima, A. Narita, N. Nishio, Y. Nakazawa, H. Iwafuchi, K. Watanabe, M. Ito, S. Kojima, S. Kato, Y. Takahashi

HAEMATOLOGICA Vol. 102 page： 35 - 35 2017.6

Efficacy of neutrophil non-muscle myosin heavy chain-IIA immunofluorescence analysis in determining the pathogenicity of MYH9 variants. Reviewed International journal

Shinji Kunishima, Okuno Yusuke, Hideki Muramatsu, Daiei Kojima, Noriko Nagai, Yoshiyuki Takahashi, Seiji Kojima

Annals of hematology Vol. 96 ( 6 ) page： 1065 - 1066 2017.6

Long-term outcomes of 95 children with moderate aplastic anemia treated with horse antithymocyte globulin and cyclosporine. Reviewed International journal

Eri Nishikawa, Hiroshi Yagasaki, Asahito Hama, Hiromasa Yabe, Akira Ohara, Yoshiyuki Kosaka, Kazuko Kudo, Ryoji Kobayashi, Shouichi Ohga, Akira Morimoto, Ken-Ichiro Watanabe, Nao Yoshida, Hideki Muramatsu, Yoshiyuki Takahashi, Seiji Kojima

Pediatric blood & cancer Vol. 64 ( 5 ) 2017.5

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

BACKGROUND: Currently, the standard management of moderate aplastic anemia (MAA) has not been well described, although the superiority of the combination of antithymocyte globulin (ATG) and cyclosporine (CyA) over CyA alone has been demonstrated in terms of hematological responses and failure-free survival (FFS). PROCEDURE: We adopted this therapeutic strategy and treated 95 children with MAA who were enrolled in two consecutive prospective studies between October 1992 and August 2009. RESULTS: For these patients, the 6-month response rate was 54.7% (complete response, 13.7%; partial response, 41.1%). There were no statistically significant differences in the overall response rates between the transfusion-dependent (48.8%, n = 41) and transfusion-independent groups (59.3%, n = 54; P = 0.4). Treatment failure was defined as the requirement of salvage treatment, and was observed in 52 patients. The 10-year FFS was 44.0% (95% confidence interval [CI], 32.9%-54.6%). Of the 22 patients who underwent a second immunosuppressive therapy (IST), 12 responded. Forty patients underwent hematopoietic stem cell transplantation as second- or third-line therapy and three died of complications. Consequently, the 10-year overall survival rate was 96.0% (95% CI, 88.0%-98.7%) with a median follow-up period of 103 months (range, 29-221 months). CONCLUSIONS: Although current guidelines recommend only observation for patients with transfusion-independent MAA, the results of our study justify early intervention with ATG and CyA in those patients. A prospective randomized trial is warranted to clarify the risks and benefits of early intervention with IST and observation alone until progression to severe AA in patients with MAA.

DOI： 10.1002/pbc.26305

Paroxysmal nonepileptic events in children with epilepsy. Reviewed International journal

Yuji Ito, Hiroyuki Kidokoro, Tamiko Negoro, Masaharu Tanaka, Yu Okai, Yoko Sakaguchi, Chikako Ogawa, Tomoya Takeuchi, Atsuko Ohno, Hiroyuki Yamamoto, Tomohiko Nakata, Satoshi Maesawa, Kazuyoshi Watanabe, Yoshiyuki Takahashi, Jun Natsume

Epilepsy research Vol. 132 page： 59 - 63 2017.5

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

OBJECTIVE: The aim of this study was to clarify the characteristics of paroxysmal nonepileptic events (PNEs) suspected as being epileptic seizures by families of children with epilepsy. METHODS: The video-EEG (vEEG) recordings of habitual paroxysmal events in children with epilepsy at Nagoya University Hospital between October 2006 and January 2016 were reviewed. Based on the doctor's suspicion before the vEEG, the PNEs were divided into two groups that included PNEs suspected as epileptic seizures and PNEs suspected as PNEs. PNEs in the former group were classified based on the suspected seizure type. RESULTS: Of 886 habitual paroxysmal events, vEEG confirmed that 83 events (68 children) were PNEs. The median age of the 68 children was 3.2 years. Concurrent epilepsies included focal epilepsies (n=33), infantile spasms (n=16), and other types (n=19). The most common types of PNEs were sleep myoclonus (n=11), followed by stereotypies (n=9), awake myoclonus (n=8), paroxysmal ocular deviations (PODs, n=8), and tonic posturing (n=8). Even after direct observation or video viewing, the doctors suspected epileptic seizures in all three of the PODs and two of the tonic posturing children. Before the vEEG, however, the accurate visual information led to the speculation that the four psychogenic and two sleep myoclonus events were all PNEs. Myoclonus, stereotypies, and head drops were often misdiagnosed as epileptic spasms, while PODs and tonic posturing were often misdiagnosed as focal seizures with motor components. Additionally, staring and motion arrest during a drowsy state were often misdiagnosed as focal dyscognitive seizures. Seven of eight patients with PODs had epileptic spasms that were concurrent with epileptic seizures. A diffuse cerebral lesion or reduced visual acuity was seen in seven patients with PODs. CONCLUSION: We re-emphasize that vEEG is essential for accurate diagnosis and provides evidence for listing POD in the differential diagnosis of oculomotor paroxysmal events.

DOI： 10.1016/j.eplepsyres.2017.02.009

PiggyBac Mediated T Cells Expressing Anti CD19 Chimeric Antigen Receptor for a Clinical Trial

Nobuhiro Nishio, Yozo Nakazawa, Motoharu Hamada, Satoshi Suzuki, Miyuki Tanaka, Daisuke Morita, Nozomu Kawashima, Yusuke Okuno, Atsushi Narita, Asahito Hama, Hideki Muramatsu, Hideki Muramatsu, Seiji Kojima, Yoshiyuki Takahashi

MOLECULAR THERAPY Vol. 25 ( 5 ) page： 291 - 291 2017.5

Germline IKAROS mutation associated with primary immunodeficiency that progressed to T-cell acute lymphoblastic leukemia Reviewed

N. Yoshida, H. Sakaguchi, H. Muramatsu, Y. Okuno, C. Song, S. Dovat, A. Shimada, M. Ozeki, H. Ohnishi, T. Teramoto, T. Fukao, N. Kondo, Y. Takahashi, K. Matsumoto, K. Kato, S. Kojima

LEUKEMIA Vol. 31 ( 5 ) page： 1221 - 1223 2017.5

Early germinal vesicle breakdown is a predictor of high preimplantation developmental competent oocytes in mice Reviewed

Shogo Higaki, Masao Kishi, Keisuke Koyama, Masashi Nagano, Seiji Katagiri, Tatsuyuki Takada, Yoshiyuki Takahashi

ZYGOTE Vol. 25 ( 1 ) page： 41 - 48 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：CAMBRIDGE UNIV PRESS

The preselection of highly developmentally competent oocytes for in vitro maturation (IVM) is crucial for improving assisted reproductive technology. Although several intrinsic markers of oocyte quality are known to be closely related to the onset of nuclear maturation (germinal vesicle break down, GVBD), a direct comparison between GVBD timing and oocyte quality has never been reported. In this study, we established a non-invasive oocyte evaluation method based on GVBD timing for preselecting more developmental competent oocytes in mice. Because the O-2 concentration during IVM may affect the nuclear kinetics, all experiments were performed under two distinct O-2 concentrations: 20% and 5% O-2. First, we determined the time course of changes in nuclear maturation and preimplantation developmental competence of in vitro-matured oocytes to estimate GVBD timing in high developmental competent oocytes. Two-thirds of oocytes that underwent GVBD in early IVM seemed to mainly contribute to the blastocyst yield. To confirm this result, we compared the preimplantation developmental competence of the early and late GVBD oocytes. Cleavage and blastocyst formation rates of early GVBD oocytes (80.2% and 52.7% under 20% O-2, respectively, and 67.6% and 47.3% under 5% O-2, respectively) were almost double those of late GVBD oocytes (44.8% and 26.0% under 20% O-2, respectively, and 40.4% and 17.9% under 5% O-2, respectively). With no observable alterations by checking the timing of GVBD in preimplantation developmental competence, oocyte evaluation based on GVBD timing can be used as an efficient and non-invasive preselection method for high developmental competent oocytes.

DOI： 10.1017/S0967199416000290

Investigation of a Rotavirus Gastroenteritis Outbreak among Immunosuppressed Patients in a Hospital Setting.

Sugata K, Hull J, Wang H, Foytich K, Moon SS, Takahashi Y, Kojima S, Yoshikawa T, Jiang B

Journal of immunological techniques in infectious diseases Vol. 6 ( 1 ) 2017.1

Clinical utility of next-generation sequencing-based minimal residual disease in paediatric B-cell acute lymphoblastic leukaemia. Reviewed International journal Open Access

Yuko Sekiya, Yinyan Xu, Hideki Muramatsu, Yusuke Okuno, Atsushi Narita, Kyogo Suzuki, Xinan Wang, Nozomu Kawashima, Hirotoshi Sakaguchi, Nao Yoshida, Asahito Hama, Yoshiyuki Takahashi, Koji Kato, Seiji Kojima

British journal of haematology Vol. 176 ( 2 ) page： 248 - 257 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

We assessed the clinical utility of next-generation sequencing (NGS)-based monitoring of minimal residual disease (MRD) in a uniformly treated cohort of 79 patients with paediatric B-cell acute lymphoblastic leukaemia. Bone marrow samples were collected at the time of diagnosis, days 33 and 80, pre- (4-5 months) and post- (24 months) maintenance therapy time points, and at relapse. We identified leukaemia-specific CDR3 sequences in 72 of 79 patients (91%) and detected MRD in 59 of 232 samples. Although MRD was detected in 28 of 55 samples (51%) on day 33, the frequencies of MRD detection decreased to 25% (16/65) at day 80, 19% (11/58) at 4-5 months and 7·4% (4/54) at 24 months. In a univariate analysis, positive MRD results on day 80 [relative risk (RR) 95% confidence interval (CI) = 7·438 (2·561-21·6), P < 0·001], at 4-5 months [RR (95% CI) = 10·24 (3·374-31·06), P < 0·001], and at 24 months [RR (95% CI) = 19·26 (4·974-74·59), P < 0·001] exhibited statistically significant associations with inferior leukaemia-free survival; this was confirmed using a Cox proportional hazard model. Our study suggests the promising potential of NGS-MRD for patients with B-cell ALL.

DOI： 10.1111/bjh.14420