Papers - SATO, Yoshiaki

Clinical factors related to bilirubin encephalopathy in preterm infants: A case-control study. Reviewed

Okumura A, Hayakawa M, Arai H, Maruo Y, Kusaka T, Kunikata T, Iwatani S, Sato Y, Morioka I

Brain & development   Vol. 47 ( 2 ) page： 104342   2025.4

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DOI： 10.1016/j.braindev.2025.104342

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Characteristics of neonatal-onset and presumed neonatal arterial ischemic stroke Reviewed

Ueda K, Kataoka E, Natsume J, Hori I, Tsuji T, Miyake M, Suzuki M, Kobayashi S, Kurahashi H, Sato Y, Okumura A, Yoshikawa T, Saitoh S, Takahashi Y.

Brain and Development     2025.3

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

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

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DOI： 10.1007/s00247-025-06194-6

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

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

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DOI： 10.1136/archdischild-2024-327942

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Development and validation of a prediction model for bronchopulmonary dysplasia using respiratory severity score. Reviewed

Kanzawa T, Kinoshita F, Namba F, Tanaka T, Oshiro M, Sugiura T, Kato Y, Miyata M, Yamada Y, Iwata O, Hayakawa M, Sato Y, BPD Prediction Model Collaborative Clinical Research Team, Neonatal Research Network of Japan

Pediatric research     2025.2

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DOI： 10.1038/s41390-025-03862-z

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Isolated congenital diaphragmatic hernia and three-year neurodevelopmental outcomes Reviewed

Toyoshima, K; Aoki, H; Katsumata, K; Sato, Y; Inoue, H; Ito, M; Amari, S; Maruyama, H; Arahori, H; Kondo, T; Kim, K; Yamoto, M; Saito, T; Okuyama, H; Usui, N; Terui, K; Nagata, K; Japanese Congenital Diaphragmatic Hernia Study Grp

PEDIATRIC RESEARCH     2025.1

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DOI： 10.1038/s41390-025-03870-z

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Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders Reviewed

Fuma, K; Iitani, Y; Imai, K; Ushida, T; Tano, S; Yoshida, K; Yokoi, A; Miki, R; Kidokoro, H; Sato, Y; Hara, Y; Ogi, T; Nomaki, K; Tsuda, M; Komine, O; Yamanaka, K; Kajiyama, H; Kotani, T

COMMUNICATIONS BIOLOGY   Vol. 8 ( 1 ) page： 75   2025.1

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DOI： 10.1038/s42003-025-07511-3

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Updates on neonatal cell and novel therapeutics: Proceedings of the Second Neonatal Cell Therapies Symposium (2024) Reviewed

Paton, MCB; Benders, M; Blatch-Williams, R; Dallimore, E; Edwards, A; Elwood, N; Facer, K; Finch-Edmondson, M; Garrity, N; Gordon, A; Hunt, RW; Jenkin, G; Mcdonald, CA; Moore, J; Nold, MF; Novak, I; Popat, H; Salomon, C; Sato, Y; Tolcos, M; Wixey, JA; Yawno, T; Zhou, LD; Malhotra, A

PEDIATRIC RESEARCH     2025.1

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DOI： 10.1038/s41390-025-03856-x

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Early Discontinuation of Steroid Treatment in Children with Abdominal Pain due to IgA Vasculitis Reviewed

European Journal of Pediatrics     2025

Risk factors of undescended testis in congenital diaphragmatic hernia: A multicenter study in Japan Reviewed

Journal of Pediatric Surgery     2025

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

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

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DOI： 10.1093/sleep/zsae225

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Safety and tolerability of a Muse cell-based product in neonatal hypoxic-ischemic encephalopathy with therapeutic hypothermia (SHIELD trial) Reviewed

Sato, Y; Shimizu, S; Ueda, K; Suzuki, T; Suzuki, S; Miura, R; Ando, M; Tsuda, K; Iwata, O; Muramatsu, Y; Kidokoro, H; Hirakawa, A; Hayakawa, M

STEM CELLS TRANSLATIONAL MEDICINE   Vol. 13 ( 11 ) page： 1053 - 1066   2024.10

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DOI： 10.1093/stcltm/szae071

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Effect of chorioamnionitis on postnatal growth in very preterm infants: a population-based study in Japan. Reviewed

Ushida T, Nosaka R, Nakatochi M, Kobayashi Y, Tano S, Fuma K, Matsuo S, Imai K, Sato Y, Hayakawa M, Kajiyama H, Kotani T, Neonatal Research Network of Japan

Archives of gynecology and obstetrics     2024.10

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DOI： 10.1007/s00404-024-07757-y

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Impact of antenatal corticosteroids-to-delivery interval on very preterm neonatal outcomes: a retrospective study in two tertiary centers in Japan. Reviewed

Fuma K, Kotani T, Tsuda H, Oshiro M, Tano S, Ushida T, Imai K, Sato Y, Kajiyama H

BMC pregnancy and childbirth   Vol. 24 ( 1 ) page： 607   2024.9

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DOI： 10.1186/s12884-024-06790-8

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

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

EARLY HUMAN DEVELOPMENT   Vol. 196   page： 106098   2024.9

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DOI： 10.1016/j.earlhumdev.2024.106098

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Impact of antenatal corticosteroids on subcortical volumes in preterm infants at term-equivalent age: A retrospective observational study. Reviewed

Fuma K, Ushida T, Kawaguchi M, Nosaka R, Kidokoro H, Tano S, Imai K, Sato Y, Hayakawa M, Kajiyama H, Kotani T

European journal of obstetrics, gynecology, and reproductive biology   Vol. 302   page： 7 - 14   2024.8

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DOI： 10.1016/j.ejogrb.2024.08.034

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Intraoperative surgical complications of open surgery for congenital diaphragmatic hernia: a multicenter, observational study in Japan Reviewed

Terui, K; Nagata, K; Yamoto, M; Sato, Y; Okuyama, H; Maruyama, H; Yokoi, A; Kim, K; Masumoto, K; Okazaki, T; Inamura, N; Toyoshima, K; Koike, Y; Yazaki, Y; Sato, Y; Usui, N

PEDIATRIC SURGERY INTERNATIONAL   Vol. 40 ( 1 ) page： 240   2024.8

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DOI： 10.1007/s00383-024-05826-6

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A Netherton syndrome infant complicated with infective endocarditis Reviewed

Tago, M; Takeichi, T; Suzuki, Y; Yoshikawa, T; Sato, Y; Kato, T; Go, K; Sakaida, T; Muro, Y; Akiyama, M

JOURNAL OF DERMATOLOGY   Vol. 52 ( 1 ) page： e12 - e13   2024.7

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DOI： 10.1111/1346-8138.17382

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Intrauterine exposure to chorioamnionitis and neuroanatomical alterations at term-equivalent age in preterm infants Reviewed

Nosaka, R; Ushida, T; Kidokoro, H; Kawaguchi, M; Shiraki, A; Iitani, Y; Imai, K; Nakamura, N; Sato, Y; Hayakawa, M; Natsume, J; Kajiyama, H; Kotani, T

ARCHIVES OF GYNECOLOGY AND OBSTETRICS   Vol. 309 ( 5 ) page： 1909 - 1918   2024.5

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DOI： 10.1007/s00404-023-07064-y

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Total Hydrocortisone Dosage in the Neonatal Period May Be Related to Low Developmental Quotient in Extremely Low Birth Weight Infants: A Retrospective Cohort Study. Reviewed International journal

Akinobu Taniguchi, Kazuki Nishida, Toshihiko Suzuki, Erina Kataoka, Naozumi Fujishiro, Eiko Kato, Hikaru Yamamoto, Koji Takemoto, Miharu Ito, Seiji Hayashi, Yuichiro Sugiyama, Takashi Maeda, Yoshiyuki Takahashi, Yoshiaki Sato

Neonatology   Vol. 121 ( 2 ) page： 195 - 202   2024.3

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INTRODUCTION: The effects of hydrocortisone (HDC) administration to extremely low birth weight (ELBW) infants on later development remain unclear. This study examined the association between HDC dosage during neonatal period and neurodevelopmental outcomes in ELBW infants. METHODS: This study was a retrospective cohort study conducted in eight centers in Japan. The subjects of this study were ELBW infants born between April 2015 and March 2017. The association between postnatal total HDC dosage up to 36 weeks postmenstrual age and the developmental quotient (DQ) at 3 years of age was examined. Multiple linear regression evaluated the association, adjusting for weeks of gestation, birth weight, and the presence of bronchopulmonary dysplasia, late-onset circulatory collapse, intracranial hemorrhage, necrotizing enterocolitis, and sepsis. RESULTS: This study included 218 ELBW infants, of whom 144 underwent a developmental test at 3 years of age. Simple linear regression analysis revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: -2.65, 95% CI: -3.73, -1.57). Multiple linear regression analysis adjusted for the presence of bronchopulmonary dysplasia and late-onset circulatory collapse also revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: -2.66, 95% CI: -3.89, -1.42). CONCLUSION: Higher total HDC dosage up to 36 weeks postmenstrual age in ELBW infants was associated with impaired neurodevelopmental outcomes. Although HDC is often needed in the treatment of ELBW infants, clinicians should be aware that an increased dose of HDC may be associated with impaired neurodevelopmental outcomes.

DOI： 10.1159/000534934

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PubMed

Next-generation sequencing-based detection of Ureaplasma in the gastric fluid of neonates with respiratory distress and chorioamnionitis. Reviewed International journal

Toshihiko Okumura, Kazuhiro Horiba, Nobuyuki Tetsuka, Yoshiaki Sato, Yuichiro Sugiyama, Kazunori Haruta, Makoto Yamaguchi, Takako Suzuki, Yuka Torii, Jun-Ichi Kawada, Tomoo Ogi, Masahiro Hayakawa, Yoshinori Ito

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians   Vol. 36 ( 1 ) page： 2207113 - 2207113   2023.12

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BACKGROUND: Respiratory distress is common in neonates admitted to neonatal intensive care units. Additionally, infectious diseases such as intrauterine infections or vertical transmission are important underlying causes of respiratory failure. However, pathogens often cannot be identified in neonates, and there are many cases in which antibacterial drugs are empirically administered. Next-generation sequencing (NGS) is advantageous in that it can detect trace amounts of bacteria that cannot be detected by culturing or bacteria that are difficult to cultivate. However, there are few reports on the diagnosis of infectious diseases using NGS in the neonatal field, especially those targeting respiratory distress. OBJECTIVE: The purpose of our study was to investigate the microorganisms associated with neonatal respiratory distress and to determine whether less invasive collection specimens such as plasma and gastric fluid are useful. METHODS: Neonates were prospectively recruited between January and August 2020 from Nagoya University Hospital. The inclusion criteria were as follows: 1) admission to the neonatal intensive care unit; 2) respiratory distress presentation within 48 h of birth; and 3) suspected infection, collection of blood culture, and administration of antibiotics. Plasma samples and blood cultures were simultaneously collected. Gastric fluid samples were also collected if the patient was not started on enteral nutrition. Information on the patients and their mothers were collected from the medical records. DNA was extracted from 140 µL of plasma and gastric fluid samples. DNA sequencing libraries were prepared, and their quality was analyzed. DNA libraries were sequenced using high-throughput NGS. The NGS data of plasma and gastric fluid samples were analyzed using the metagenomic pipeline PATHDET, which calculated the number of reads assigned to microorganisms and their relative abundance. Putative pathogens were listed. RESULTS: Overall, 30 plasma samples and 25 gastric fluid samples from 30 neonates were analyzed. Microorganism-derived reads of gastric fluid samples were significantly higher than those of plasma samples. Transient tachypnea of the newborn was the most common cause of respiratory distress with 13 cases (43%), followed by respiratory distress syndrome with 7 cases (23%). There were 8 cases (29%) of chorioamnionitis and 7 cases (25%) of funisitis pathologically diagnosed. All blood cultures were negative, and only two gastric fluid cultures were positive for group B Streptococcus (Patient 15) and Candida albicans (Patient 24). Putative pathogens that met the positive criteria for PATHET were detected in four gastric fluid samples, one of which was group B Streptococcus from Patient 15. In the gastric fluid sample of Patient 24, Candida albicans were detected by NGS but did not meet the positive criteria for PATHDET. Cluster analysis of the plasma samples divided them into two study groups, and the indicator genera of each cluster (Phormidium or Toxoplasma) are shown in Figure 1. Clinical findings did not show any significant differences between the two groups. Cluster analysis of the gastric fluid samples divided them into three study groups, and the indicator genera of each cluster (Ureaplasma, Nostoc, and Streptococcus) are shown in Figure 2. The incidence rate of chorioamnionitis was significantly higher in Ureaplasma group than in the other two groups. CONCLUSION: Gastric fluid may be useful for assessing neonatal patients with respiratory distress. To the best of our knowledge, this was the first study to reveal that the presence of Ureaplasma in the gastric fluid of neonates with respiratory distress was associated with chorioamnionitis. The early diagnosis of intra-amniotic infections using gastric fluid and its treatment may change the treatment strategy for neonatal respiratory distress. Screening for Ureaplasma in neonates with respiratory distress may reduce the need for empirical antibiotic administration. Further research is required to confirm these findings.

DOI： 10.1080/14767058.2023.2207113

PubMed

Antenatal corticosteroids and outcomes of small for gestational age infants born at 24-31 gestational weeks: a population-based propensity score matching analysis. Reviewed International journal

Takafumi Ushida, Masahiro Nakatochi, Yumiko Kobayashi, Noriyuki Nakamura, Kazuya Fuma, Yukako Iitani, Kenji Imai, Yoshiaki Sato, Masahiro Hayakawa, Hiroaki Kajiyama, Tomomi Kotani

Archives of gynecology and obstetrics   Vol. 308 ( 5 ) page： 1463 - 1471   2023.11

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PURPOSE: To evaluate the effect of antenatal corticosteroid (ACS) treatment on neonatal outcomes in small for gestational age (SGA) infants born at 24-31 gestational weeks compared with non-SGA infants. METHODS: A population-based retrospective study was conducted that analyzed clinical data from the Neonatal Research Network of Japan database, which enrolls neonates born at < 32 gestational weeks and weighing 1500 g or less (n = 22,414). Propensity score matching (with the ratio of ACS to no-ACS groups of 1:1) was performed in SGA (n = 7028) and non-SGA (n = 15,386) infants, respectively. Univariate logistic and interaction analyses were performed to compare the short-term neonatal outcomes of infants with and without ACS treatment in utero. RESULTS: In the SGA and non-SGA infants, ACS treatment significantly reduced in-hospital mortality (odds ratio 0.67 95% confidence interval [0.50-0.88] and 0.62 [0.50-0.78], respectively), respiratory distress syndrome (0.77 [0.69-0.87] and 0.63 [0.58-0.68], respectively), and composite adverse outcomes (0.73 [0.58-0.91] and 0.57 [0.50-0.65], respectively). ACS treatment also significantly reduced intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, and sepsis in the non-SGA infants, but not in the SGA infants. However, interaction analyses revealed no significant differences between the SGA and non-SGA infants in the efficacy of ACS treatment on short-term outcomes except for respiratory distress syndrome. CONCLUSIONS: ACS treatment was associated with beneficial effects on mortality, respiratory distress syndrome, and adverse composite outcomes in extremely and very preterm SGA infants, with similar efficacy on all neonatal outcomes except for respiratory distress syndrome observed in the non-SGA infants.

DOI： 10.1007/s00404-022-06834-4

PubMed

Various Organ Damages in Rats with Fetal Growth Restriction and Their Slight Attenuation by Bifidobacterium breve Supplementation. Reviewed

Tsuji M, Tanaka N, Koike H, Sato Y, Shimoyama Y, Itoh A

Life (Basel, Switzerland)   Vol. 13 ( 10 )   2023.10

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DOI： 10.3390/life13102005

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Systemic administration of clinical-grade multilineage-differentiating stress-enduring cells ameliorates hypoxic-ischemic brain injury in neonatal rats. Reviewed International journal

Kazuto Ueda, Yoshiaki Sato, Shinobu Shimizu, Toshihiko Suzuki, Atsuto Onoda, Ryosuke Miura, Shoji Go, Haruka Mimatsu, Yuma Kitase, Yuta Yamashita, Keiichi Irie, Masahiro Tsuji, Kenichi Mishima, Masaaki Mizuno, Yoshiyuki Takahashi, Mari Dezawa, Masahiro Hayakawa

Scientific reports   Vol. 13 ( 1 ) page： 14958 - 14958   2023.9

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Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic-ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 106 cells/body) or Hank's balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel.

DOI： 10.1038/s41598-023-41026-3

PubMed

Vascular perforation of umbilical venous catheter and awaiting it to be shallow. Reviewed

Taniguchi A, Hayakawa M, Sato Y

Nagoya journal of medical science   Vol. 85 ( 3 ) page： 635 - 638   2023.8

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DOI： 10.18999/nagjms.85.3.635

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Dedifferentiated fat cells administration ameliorates abnormal expressions of fatty acids metabolism-related protein expressions and intestinal tissue damage in experimental necrotizing enterocolitis Reviewed

Haruka Mimatsu, Atsuto Onoda, Tomohiko Kazama, Koji Nishijima, Yoshie Shimoyama, Shoji Go, Kazuto Ueda, Yoshiyuki Takahashi, Taro Matsumoto, Masahiro Hayakawa, Yoshiaki Sato

Scientific Reports   Vol. 13 ( 1 ) page： 8266   2023.5

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Abstract

Neonatal necrotizing enterocolitis (NEC) is a serious disease of premature infants that necessitates intensive care and frequently results in life-threatening complications and high mortality. Dedifferentiated fat cells (DFATs) are mesenchymal stem cell-like cells derived from mature adipocytes. DFATs were intraperitoneally administrated to a rat NEC model, and the treatment effect and its mechanism were evaluated. The NEC model was created using rat pups hand fed with artificial milk, exposed to asphyxia and cold stress, and given oral lipopolysaccharides after cesarean section. The pups were sacrificed 96 h after birth for macroscopic histological examination and proteomics analysis. DFATs administration significantly improved the survival rate from 25.0 (vehicle group) to 60.6% (DFAT group) and revealed a significant reduction in macroscopical, histological, and apoptosis evaluation compared with the vehicle group. Additionally, the expression of C–C motif ligand 2 was significantly decreased, and that of interleukin-6 decreased in the DFAT group. DFAT administration ameliorated 93 proteins mainly related to proteins of fatty acid metabolism of the 436 proteins up-/down-regulated by NEC. DFATs improved mortality and restored damaged intestinal tissues in NEC, possibly by improving the abnormal expression of fatty acid-related proteins and reducing inflammation.

DOI： 10.1038/s41598-023-34156-1

PubMed

Other Link： https://www.nature.com/articles/s41598-023-34156-1

Antenatal corticosteroids-to-delivery interval associates cord blood S100B levels. Reviewed International journal

Kazuya Fuma, Tomomi Kotani, Takafumi Ushida, Kenji Imai, Yukako Iitani, Noriyuki Nakamura, Rika Miki, Satoru Katsuki, Fumie Kinoshita, Yoshiaki Sato, Masahiro Hayakawa, Hiroaki Kajiyama

The journal of obstetrics and gynaecology research   Vol. 49 ( 4 ) page： 1129 - 1136   2023.4

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AIM: Antenatal corticosteroids (ACS) are recommended for women at risk of preterm birth before 34 weeks' gestation. However, adverse effects of ACS on the fetal brain have also been reported. The time interval from ACS administration to delivery (ACS-to-delivery interval) might alter the effect of ACS on the fetal brain. This study aimed to evaluate the effect of ACS-to-delivery interval on cord blood S100 calcium-binding protein B (S100B) levels as a biomarker of brain damage. METHODS: Women who delivered between 2012 and 2020 at a tertiary medical center were divided into three groups according to ACS use and ACS-to-delivery interval, retrospectively: non-ACS, ACS ≤7 days, and ACS >7 days. Patients who did not complete the ACS regimen were excluded. The primary outcome was cord blood S100B levels. RESULTS: Cord blood S100B levels were significantly lower in the ACS ≤7 days group than in the non-ACS and ACS >7 days groups. In the multiple regression analysis, birth ≤7 days after ACS showed a significant negative association with S100B level (p < 0.001). CONCLUSIONS: Reduced S100B levels were observed in infants born ≤7 days after ACS but not in infants born >7 days after ACS. These findings suggest the importance of ACS timing to optimize its effects on the fetal brain, although further studies are required to identify these mechanisms.

DOI： 10.1111/jog.15582

PubMed

Umbilical cord-derived mesenchymal stromal cell therapy to prevent the development of neurodevelopmental disorders related to low birth weight. Reviewed

Tsuji M, Mukai T, Sato Y, Azuma Y, Yamamoto S, Cayetanot F, Bodineau L, Onoda A, Nagamura-Inoue T, Coq JO

Scientific reports   Vol. 13 ( 1 ) page： 3841   2023.3

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DOI： 10.1038/s41598-023-30817-3

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

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

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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

PubMed

Refractory pneumothorax due to tracheal laceration in extremely preterm infant. Reviewed

Maeda T, Suzuki T, Mizutani K, Hasegawa H, Sato Y

Pediatrics international : official journal of the Japan Pediatric Society   Vol. 65 ( 1 ) page： e15698   2023.1

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DOI： 10.1111/ped.15698

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Case report: High-dose epoprostenol therapy in pediatric patients with pulmonary hypertension and developmental lung disease Reviewed

Yoshie Fukasawa, Hidenori Yamamoto, Miharu Ito, Akiko Saito, Kiyotaka Go, Yoshihito Morimoto, Kazushi Yasuda, Yoshiaki Sato, Masahiro Hayakawa, Taichi Kato

Frontiers in Pediatrics   Vol. 11   page： 1116434   2023

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Pulmonary hypertension (PH) with developmental lung disease is a life-threatening disease and accounts for 10%–12% of pediatric PH patients. Administration of specific pulmonary vasodilators to pediatric PH patients has brought about improvement of their long-term prognosis. Intravenous epoprostenol therapy is a gold standard therapy for severe idiopathic pulmonary arterial hypertension (IPAH), but there are few reports demonstrating the efficacy of epoprostenol for pediatric PH patients with developmental lung disease, especially when treating with high doses of epoprostenol. Two cases of pediatric PH patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) and congenital diaphragmatic hernia (CDH) with bronchopulmonary dysplasia (BPD), respectively, treated with epoprostenol above 100 ng/kg/min are presented. In these two cases, severe PH was improved significantly by an aggressive increase of the epoprostenol infusion rate with administration of oral pulmonary vasodilators and appropriate respiratory management, without any significant adverse effects. High-dose epoprostenol therapy may be one of the therapeutic options in pediatric PH patients with developmental lung disease.

DOI： 10.3389/fped.2023.1116434

PubMed

Altered offspring neurodevelopment in an L-NAME-induced preeclampsia rat model Reviewed

Noriyuki Nakamura, Takafumi Ushida, Atsuto Onoda, Kazuto Ueda, Ryosuke Miura, Toshihiko Suzuki, Satoru Katsuki, Hidesuke Mizutani, Kosuke Yoshida, Sho Tano, Yukako Iitani, Kenji Imai, Masahiro Hayakawa, Hiroaki Kajiyama, Yoshiaki Sato, Tomomi Kotani

Frontiers in Pediatrics   Vol. 11   page： 1168173   2023

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Introduction

To investigate the mechanism underlying the increased risk of subsequent neurodevelopmental disorders in children born to mothers with preeclampsia, we evaluated the neurodevelopment of offspring of a preeclampsia rat model induced by the administration of N-nitro-L-arginine methyl ester (L-NAME) and identified unique protein signatures in the offspring cerebrospinal fluid.

Methods

Pregnant rats received an intraperitoneal injection of L-NAME (250 mg/kg/day) during gestational days 15–20 to establish a preeclampsia model. Behavioral experiments (negative geotaxis, open-field, rotarod treadmill, and active avoidance tests), immunohistochemistry [anti-neuronal nuclei (NeuN) staining in the hippocampal dentate gyrus and cerebral cortex on postnatal day 70], and proteome analysis of the cerebrospinal fluid on postnatal day 5 were performed on male offspring.

Results

Offspring of the preeclampsia dam exhibited increased growth restriction at birth (52.5%), but showed postnatal catch-up growth on postnatal day 14. Several behavioral abnormalities including motor development and vestibular function (negative geotaxis test: p &amp;lt; 0.01) in the neonatal period; motor coordination and learning skills (rotarod treadmill test: p = 0.01); and memory skills (active avoidance test: p &amp;lt; 0.01) in the juvenile period were observed. NeuN-positive cells in preeclampsia rats were significantly reduced in both the hippocampal dentate gyrus and cerebral cortex (p &amp;lt; 0.01, p &amp;lt; 0.01, respectively). Among the 1270 proteins in the cerebrospinal fluid identified using liquid chromatography-tandem mass spectrometry, 32 were differentially expressed. Principal component analysis showed that most cerebrospinal fluid samples achieved clear separation between preeclampsia and control rats. Pathway analysis revealed that differentially expressed proteins were associated with endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins, which are involved in various nervous system disorders including autism spectrum disorders, schizophrenia, and Alzheimer's disease.

Conclusion

The offspring of the L-NAME-induced preeclampsia model rats exhibited key features of neurodevelopmental abnormalities on behavioral and pathological examinations similar to humans. We found altered cerebrospinal fluid protein profiling in this preeclampsia rat, and the unique protein signatures related to endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins may be associated with subsequent adverse neurodevelopment in the offspring.

DOI： 10.3389/fped.2023.1168173

PubMed

末梢挿入式中心静脈カテーテル(PICC)長期留置後の抜去困難症例　PICC抜去困難症の対応手順の作成 Reviewed

橋本佑樹、村松友佳子、伊藤美春、齊藤明子、佐藤義朗、早川昌弘

日本新生児成育医学会雑誌   Vol. 35 ( 1 ) page： 91－94   2023

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

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

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Authorship：Last author   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 &amp;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 &amp;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 &amp;lt; .001) and hospitalization stay (5.7 vs 6.0 days, P &amp;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

PubMed

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

Impact of hypertensive disorders of pregnancy on respiratory outcomes in extremely and very preterm infants: A population-based study in Japan. Reviewed International journal

Takafumi Ushida, Noriyuki Nakamura, Masahiro Nakatochi, Yumiko Kobayashi, Yoshiaki Sato, Yukako Iitani, Kenji Imai, Tomoko Nakano-Kobayashi, Masahiro Hayakawa, Hiroaki Kajiyama, Tomomi Kotani

Pregnancy hypertension   Vol. 29   page： 54 - 60   2022.8

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OBJECTIVES: We aimed to evaluate the impact of hypertensive disorders of pregnancy (HDP) on short- and medium-term respiratory outcomes in extremely and very preterm infants using the Neonatal Research Network of Japan database. STUDY DESIGN: This was a population-based retrospective study of preterm infants weighing ≤ 1500 g born between 22 and 31 weeks of gestation between 2003 and 2017. After 1:1 stratification matching by four factors (maternal age, gestational age, parity, and year of delivery), a total of 5137 infants in each group (HDP and non-HDP groups) were selected. MAIN OUTCOME MEASURES: The association between HDP and various respiratory outcomes was evaluated using univariate and multivariate logistic regression analyses. RESULTS: In the multivariate analyses, HDP was associated with higher odds for respiratory distress syndrome (RDS) (odds ratio 1.83, 95% confidence interval [1.65-2.03]), but reduced odds of persistent pulmonary hypertension of the newborn (PPHN) (0.34 [0.26-0.46]) and inhaled nitric oxide use (0.43 [0.33-0.55]). Although HDP was associated with an increased risk of chronic lung disease (CLD) in the univariate analysis, this association was not significant after adjustment for covariates (0.94 [0.83-1.07]). No significant association was found between HDP and home oxygen therapy (HOT) and medium-term oxygen use. CONCLUSION: The impact of maternal HDP largely differed depending on respiratory disorders and respiratory support. HDP was associated with higher odds of RDS but reduced odds of PPHN. The risks for CLD, HOT, and medium-term respiratory outcomes in the HDP group were comparable to those in the non-HDP group.

DOI： 10.1016/j.preghy.2022.06.003

PubMed

Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial. Reviewed International journal

Nao Matsuyama, Shinobu Shimizu, Kazuto Ueda, Toshihiko Suzuki, Sakiko Suzuki, Ryosuke Miura, Akemi Katayama, Masahiko Ando, Masaaki Mizuno, Akihiro Hirakawa, Masahiro Hayakawa, Yoshiaki Sato

BMJ open   Vol. 12 ( 4 ) page： e057073   2022.4

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INTRODUCTION: Neonatal hypoxic-ischaemic encephalopathy (HIE) is an important illness associated with death or cerebral palsy. This study aims to assess the safety and tolerability of the allogenic human multilineage-differentiating stress-enduring cell (Muse cell)-based product (CL2020) cells in newborns with HIE. This is the first clinical trial of CL2020 cells in neonates. METHODS AND ANALYSIS: This is a single-centre, open-label, dose-escalation study enrolling up to 12 patients. Neonates with HIE who receive a course of therapeutic hypothermia therapy, which cools to a body temperature of 33°C-34°C for 72 hours, will be included in this study. A single intravenous injection of CL2020 cells will be administered between 5 and 14 days of age. Subjects in the low-dose and high-dose cohorts will receive 1.5 and 15 million cells per dose, respectively. The primary outcome is the occurrence of any adverse events within 12 weeks after administration. The main secondary outcome is the Bayley Scales of Infant and Toddler Development Third Edition score and the developmental quotient per the Kyoto Scale of Psychological Development 2001 at 78 weeks. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. The Nagoya University Hospital Institutional Review Board (No. 312005) approved this study on 13 November 2019. The results of this study will be published in peer-reviewed journal and reported in international conferences. TRIAL REGISTRATION NUMBERS: NCT04261335, jRCT2043190112.

DOI： 10.1136/bmjopen-2021-057073

PubMed

Relationship between Neonatal MRI Findings and Emotional/Behavioral Evaluation in Early Childhood for Extremely Low-Birth-Weight Infants. Reviewed International journal

Akinobu Taniguchi, Masahiro Hayakawa, Erina Kataoka, Naozumi Fujishiro, Yoshiaki Sato

Journal of clinical medicine   Vol. 11 ( 3 )   2022.1

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The aim of this study is to investigate whether it is possible to detect future behavioral and emotional problems in extremely low-birth-weight infants by evaluating the neonatal head magnetic resonance imaging (MRI) using a scoring system. This study included 62 extremely low-birth-weight infants born between April 2015 and March 2017 and those who had undergone MRI at 36 to 42 weeks of gestation. These subjects were administered with the Strength and Difficulties Questionnaire (SDQ) at age 4-5, and the patients who responded to the questionnaire were included in the study. A positive correlation was observed between the Global Brain Abnormality Score and Total Difficulties Score of the SDQ (r = 0.26, p = 0.038). However, no significant difference was observed between the median Global Brain Abnormality Score of the normal and borderline-range group and the Total Difficulties Score of the clinical-range group (p = 0.51). This study demonstrated the relationship between the MRI findings in the newborn period and the emotional and behavioral problems in early childhood, but it is not clinically useful as a predictive marker.

DOI： 10.3390/jcm11030772

PubMed

Hypertensive disorders of pregnancy and alterations in brain metabolites in preterm infants: A multi-voxel proton MR spectroscopy study. Reviewed International journal

Satoru Katsuki, Takafumi Ushida, Hiroyuki Kidokoro, Noriyuki Nakamura, Yukako Iitani, Kazuya Fuma, Kenji Imai, Tomoko Nakano-Kobayashi, Yoshiaki Sato, Masahiro Hayakawa, Jun Natsume, Hiroaki Kajiyama, Tomomi Kotani

Early human development   Vol. 163   page： 105479 - 105479   2021.12

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BACKGROUND: Infants born to mothers with hypertensive disorders of pregnancy (HDP) have adverse neurodevelopmental consequences in later life. Magnetic resonance spectroscopy (MRS) is used to predict subsequent neurodevelopment in the field of perinatology. AIM: We aimed to determine whether exposure to HDP in utero leads to alterations in brain metabolites in preterm infants using multi-voxel proton MRS at term-equivalent age. STUDY DESIGN: Retrospective cohort study. SUBJECTS: A total of 103 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible. Twenty-seven infants were born to mothers with HDP (HDP group), and 76 were born to mothers without HDP (non-HDP group). OUTCOME MEASURES: The peak area ratios of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr), and Cho/Cr were evaluated at 10 designated regions of interest (bilateral frontal lobes, basal ganglia, thalami, temporal lobes, and occipital lobes). RESULTS: The peak area ratios of NAA/Cho and NAA/Cr in the bilateral thalami were significantly higher in the HDP group than in the non-HDP group after adjustment for covariates (postmenstrual age at MRS assessment and infant sex). No significant differences were observed in other regions. Preeclampsia, abnormal umbilical artery blood flow, and fetal growth restrictions were significantly associated with increased NAA/Cho and NAA/Cr ratios in the thalami. CONCLUSIONS: Based on the evidence that NAA/Cho and NAA/Cr ratios constantly increase with postmenstrual age in normal brain development, exposure to maternal HDP in utero may accelerate brain maturation and increase neuronal activity in preterm infants.

DOI： 10.1016/j.earlhumdev.2021.105479

PubMed

Trajectory of the incidence of brushes on preterm electroencephalogram and its association with neurodevelopment in extremely low birth weight infants. Reviewed International journal

Takashi Maeda, Hiroyuki Kidokoro, Takashi Tachibana, Anna Shiraki, Hiroyuki Yamamoto, Tomohiko Nakata, Tatsuya Fukasawa, Tetsuo Kubota, Yoshiaki Sato, Toru Kato, Jun Natsume, Akihisa Okumura, Masahiro Hayakawa

Brain & development   Vol. 43 ( 10 ) page： 979 - 987   2021.11

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BACKGROUND: Brush or delta brush is a well-known characteristic waveform in preterm electroencephalograms. However, the longitudinal trajectory of brushes and its association with neurodevelopment remain uncertain. METHODS: We analyzed the longitudinal incidence of brushes in 36 extremely low birth weight infants without severe brain lesions and its association with neurodevelopment and white matter abnormality. Conventional eight-channel electroencephalograms were recorded at 30, 32, 36, and 40 postmenstrual weeks (PMW). Incidence of brushes was calculated as the sum of brushes from each channel separated by active sleep and quiet sleep. A developmental delay was defined as a developmental quotient of <85 assessed at corrected age of 18 months. White matter abnormalities were evaluated with term-equivalent magnetic resonance imaging. RESULTS: The median incidence of brushes (per minute) in 36 infants at PMW 30, 32, 36, and 40 was 16.4, 20.4, 22.5, and 1.8 during active sleep and 7.5, 10.3, 11.5, and 1.7 during quiet sleep, respectively. Among the 36 infants, 14 infants were diagnosed with developmental delay. Longitudinal trajectories of the incidence of brushes were different between the normal and the delayed development groups. Brushes were observed most frequently at 36 PMW in the delayed development group. The incidence of brushes at 36 PMW was significantly correlated with the severity of white matter abnormalities and negatively correlated with the developmental quotient. CONCLUSION: The incidence of brushes at 36 PMW can be a unique predictor of early neurodevelopment in extremely low birth weight infants without severe brain lesions.

DOI： 10.1016/j.braindev.2021.07.003

PubMed

Impact of maternal hypertensive disorders of pregnancy on brain volumes at term-equivalent age in preterm infants: A voxel-based morphometry study. Reviewed International journal

Takafumi Ushida, Hiroyuki Kidokoro, Noriyuki Nakamura, Satoru Katsuki, Kenji Imai, Tomoko Nakano-Kobayashi, Yoshinori Moriyama, Yoshiaki Sato, Masahiro Hayakawa, Jun Natsume, Hiroaki Kajiyama, Tomomi Kotani

Pregnancy hypertension   Vol. 25   page： 143 - 149   2021.8

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OBJECTIVES: Infants born to mothers with hypertensive disorders of pregnancy (HDP) reportedly have negative behavioral and neurodevelopmental outcomes. However, the effects of maternal HDP on infant brain growth have not been fully evaluated. We aimed to evaluate brain volumes and brain injury in preterm infants born to mothers with HDP using magnetic resonance (MR) imaging at term-equivalent age. STUDY DESIGN: In this cohort study, MR imaging was performed for 94 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018. Twenty infants were born to mothers with HDP and 74 to mothers without HDP. MAIN OUTCOME MEASURES: Total brain volumes and regional volumetric alterations were assessed by voxel-based morphometry, and brain injury was evaluated using the Kidokoro global brain abnormality score. Developmental quotient was assessed at a corrected age of 1.5 years in 59 infants (HDP, n = 11; non-HDP, n = 48). RESULTS: No significant differences were observed in the gray and white matter volumes of the two groups (HDP: 175 ± 24 mL, 137 ± 13 mL, respectively; non-HDP: 172 ± 24 mL, 142 ± 13 mL, respectively). Additionally, no regional volumetric alterations were observed between the two groups after covariate adjustment (gestational age and infant sex). The total Kidokoro score and developmental quotient were similar in both groups. CONCLUSIONS: No significant differences in the global and regional brain volumes were observed. Further research is needed to confirm our findings at different time points of MR imaging and in different populations.

DOI： 10.1016/j.preghy.2021.06.003

PubMed

Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy. Reviewed International journal

Toshihiko Suzuki, Yoshiaki Sato, Yoshihiro Kushida, Masahiro Tsuji, Shohei Wakao, Kazuto Ueda, Kenji Imai, Yukako Iitani, Shinobu Shimizu, Hideki Hida, Takashi Temma, Shigeyoshi Saito, Hidehiro Iida, Masaaki Mizuno, Yoshiyuki Takahashi, Mari Dezawa, Cesar V Borlongan, Masahiro Hayakawa

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism   Vol. 41 ( 7 ) page： 1707 - 1720   2021.7

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Perinatal hypoxic ischemic encephalopathy (HIE) results in serious neurological dysfunction and mortality. Clinical trials of multilineage-differentiating stress enduring cells (Muse cells) have commenced in stroke using intravenous delivery of donor-derived Muse cells. Here, we investigated the therapeutic effects of human Muse cells in an HIE model. Seven-day-old rats underwent ligation of the left carotid artery then were exposed to 8% oxygen for 60 min, and 72 hours later intravenously transplanted with 1 × 104 of human-Muse and -non-Muse cells, collected from bone marrow-mesenchymal stem cells as stage-specific embryonic antigen-3 (SSEA-3)+ and -, respectively, or saline (vehicle) without immunosuppression. Human-specific probe revealed Muse cells distributed mainly to the injured brain at 2 and 4 weeks, and expressed neuronal and glial markers until 6 months. In contrast, non-Muse cells lodged in the lung at 2 weeks, but undetectable by 4 weeks. Magnetic resonance spectroscopy and positron emission tomography demonstrated that Muse cells dampened excitotoxic brain glutamatergic metabolites and suppressed microglial activation. Muse cell-treated group exhibited significant improvements in motor and cognitive functions at 4 weeks and 5 months. Intravenously transplanted Muse cells afforded functional benefits in experimental HIE possibly via regulation of glutamate metabolism and reduction of microglial activation.

DOI： 10.1177/0271678X20972656

PubMed

Diverse actions of cord blood cell therapy for hypoxic-ischemic encephalopathy. Invited Reviewed International journal

Yoshiaki Sato, Masahiro Tsuji

Pediatrics international : official journal of the Japan Pediatric Society   Vol. 63 ( 5 ) page： 497 - 503   2021.5

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death and permanent neurological deficits. However, effective treatments have not yet been established, except therapeutic hypothermia, which is not effective for severe HIE; therefore, developing a novel therapy for HIE is of the utmost importance. Stem cell therapy has recently been identified as a novel therapy for HIE. Among the various stem cell sources, ethical hurdles can be avoided by using stem cells that originate from non-embryonic or non-neural tissues, such as umbilical cord blood cells (UCBCs), which are readily available and can be exploited for autologous transplantations. Human UCBs are a rich source of stem and progenitor cells. Many recent studies have reported the treatment effect of UCBCs. Additionally, phase I clinical trials have already been conducted, showing this therapy's safety and feasibility. One advantage of stem cell therapies, including UCBC administration, is that they exert treatment effects through multifaceted mechanisms. According to the findings of several publications, replacement of lost cells, namely, engraftment and differentiation into neuronal cells, is not likely to be the main mechanism. However, the association between UCBCs and various mechanism of action, such as neurogenesis, angiogenesis, and anti-inflammation, has been suggested in many studies, and most mechanisms are due to growth factors secreted from UCBCs. These diverse actions of UCBC treatment are expected to exert a substantial effect on HIE, which has a complex injury mechanism.

DOI： 10.1111/ped.14604

PubMed

Outcomes in symptomatic preterm infants with postnatal cytomegalovirus infection. Reviewed

Takemoto K, Oshiro M, Sato Y, Yamamoto H, Ito M, Hayashi S, Kato E, Kato Y, Hayakawa M

Nagoya journal of medical science   Vol. 83 ( 2 ) page： 311 - 319   2021.5

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Premature infants are at risk for developing symptomatic postnatal cytomegalovirus (CMV) disease, including sepsis-like syndrome. We performed a retrospective case-control study including infants born before 32 weeks of gestation and diagnosed with symptomatic postnatal CMV infection during the neonatal period. Neurodevelopmental outcome was evaluated using the Kyoto Scale of Psychological Development 2001 at 18 months of corrected age and at 3 years of age. Twenty-four infants were diagnosed with postnatal CMV infection; of them, 14 had sepsis-like symptoms and 10 had laboratory test abnormalities only. Home oxygen therapy was used significantly higher in the CMV-positive group compared with the control group at hospital discharge (52% vs 21%, P=0.032). The incidence of neurodevelopmental impairment was not significantly different between the two groups at 18 months of corrected age (29% vs 17%, P=0.48) and at 3 years of age (43% vs 29%, P=0.34). Postnatal CMV infection did not have a significant influence on neurodevelopmental outcomes of symptomatic preterm infants, although those in the CMV-positive group appeared worse. Larger studies with long-term follow-up are needed for a better understanding of continued neurodevelopmental outcomes in preterm infants with postnatal CMV infection.

DOI： 10.18999/nagjms.83.2.311

PubMed

A Study of Respiration Residual Template Matching Method for Neonatal Heartbeat Detection Using Doppler Sensor Reviewed

UEBAYASHI Shinji, MORI Tomoya, SATO Yoshiaki

  Vol. J104-B ( 3 ) page： 369 - 378   2021.3

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A neonatal heartbeat detection method using doppler sensor has been proposed. The method removes respiration waveform from the measured signal with template matching method synchronizing at each respiration period. The proportion of heartbeat to respiration rate of neonate decreases of 58% compared to adult, and desired effects of current frequrncy analyses will not be enough. The proposed method calculates heartbeat interval directly without frequency analyses, and measurements are stable even when the proportion is small. Through the experiments of the neonatal model which can simulate respiration and heartbet, and of an adult, we show that the measurement errors are 0.0-3.3%.

DOI： 10.14923/transcomj.2020jbp3039

CiNii Research

Brain damage caused by neonatal hypoxia-ischemia and the effects of hypothermia in severe combined immunodeficient (SCID) mice. Reviewed International journal

Yuko Ogawa, Emi Tanaka, Yoshiaki Sato, Masahiro Tsuji

Experimental neurology   Vol. 337   page： 113577 - 113577   2021.3

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Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of brain damage in newborns. Although therapeutic hypothermia has been shown to be neuroprotective against neonatal HIE in clinical trials, its effect is not satisfactory. Cell-based therapies have attracted much attention as novel treatments for HIE. Preclinical studies on a variety of human cell transplantation methods have been performed in immunodeficient/immunosuppressed animals, such as severe combined immunodeficient (SCID) mice, which lack functional T and B lymphocytes. The detailed characteristics of neonatal HIE in SCID mice, however, have not been delineated. In preclinical studies, novel therapies for neonatal HIE should be evaluated in combination with hypothermia, which has become a standard treatment for neonatal HIE. However, the effects of hypothermia in SCID mice have not been delineated. In the present study, we compared neonatal hypoxic-ischemic (HI) brain damage in SCID mice and wild-type mice treated with or without hypothermia. Male and female mouse pups were subjected to HI insult induced by unilateral common carotid artery ligation combined with systemic hypoxia on postnatal day 12. In the first 4 h after HI insult, body temperature was maintained at 36 °C for the normothermia groups or 32 °C for the hypothermia groups. The severity of brain damage in SCID mice did not differ from that in wild-type mice based on most evaluations, i.e., cerebral blood flow, hemiparesis, muscle strength, spontaneous activity, cerebral hemispheric volume, neuropathological injury, and serum cytokine levels, although spleen weight, brain weight, leukocyte counts and the levels of some cytokines in the peripheral blood were different between genotypes. The effects of hypothermia in SCID mice were comparable to those in wild-type mice based on most evaluations. Taken together, these findings indicate that SCID mice can be used as an appropriate preclinical model for cell therapies for neonatal HIE.

DOI： 10.1016/j.expneurol.2020.113577

Web of Science

PubMed

Non-invasive biosignals detection for continuous monitoring of a neonate using quartz crystal resonator Reviewed

Shiro Watanabe, Yuichi Murozaki, Hirotaka Sugiura, Yoshiaki Sato, Kazuya Honbe, Fumihito Arai

Sensors and Actuators A: Physical   Vol. 317   page： 112475 - 112475   2021.1

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DOI： 10.1016/j.sna.2020.112475

Web of Science

Muse細胞を用いた新生児低酸素性虚血性脳症の新規治療法開発 ～動物実験から探索的臨床試験（医師主導治験）まで～ Invited Reviewed

佐藤 義朗

日本周産期・新生児医学会雑誌   Vol. 56 ( 4 ) page： 586 - 589   2021

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：一般社団法人 日本周産期・新生児医学会  

<p>　<b>はじめに</b></p><p>　新生児死亡率は年々減少しているが，脳性麻痺の発症は出生1,000人に対し，1.5から2.5の間であり一向に減少の兆しがない．脳性麻痺は生涯続き，1人当たりの経済的費用は約1億円と非常に高額である．患者本人はもちろん，支える家族にとっても大きな負担となる．そのため脳性麻痺を未然に防ぐことが極めて重要である．</p><p>　周産期低酸素性虚血性脳症（HIE）は，脳性麻痺の主たる原因である．発症頻度は出生1,000人に対し1.3から1.7であるが，確立した治療は低体温療法のみである．その低体温療法も18カ月後の死亡，もしくは，重度の神経学的後遺症を減少させる治療必要数（NNT：number needed to treat）は9と効果は限定的であり，新たな治療法が望まれる．そこで，我々は幹細胞療法に着目し，研究を進めてきた．</p>

DOI： 10.34456/jjspnm.56.4_586

CiNii Research

Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains. Reviewed International journal

Tanaka E, Ogawa Y, Fujii R, Shimonaka T, Sato Y, Hamazaki T, Nagamura-Inoue T, Shintaku H, Tsuji M

Scientific reports   Vol. 10 ( 1 ) page： 21881 - 21881   2020.12

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Ischemic brain injury provokes complex, time-dependent downstream pathways that ultimately lead to cell death. We aimed to demonstrate the levels of a wide range of metabolites in brain lysates and their on-tissue distribution following neonatal stroke and cell therapies. Postnatal day 12 mice underwent middle cerebral artery occlusion (MCAO) and were administered 1 × 105 cells after 48 h. Metabolomic analysis of the injured hemisphere demonstrated that a variety of amino acids were significantly increased and that tricarboxylic acid cycle intermediates and some related amino acids, such as glutamate, were decreased. With the exception of the changes in citric acid, neither mesenchymal stem/stromal cells nor CD34+ cells ameliorated these changes. On-tissue visualization with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) imaging revealed that the signal intensity of glutamate was significantly decreased in the infarct area, consistent with the metabolomic analysis, while its intensity was significantly increased in the peri-infarct area after MCAO. Although cell therapies did not ameliorate the changes in metabolites in the infarct area, mesenchymal stem cells ameliorated the increased levels of glutamate and carnitine in the peri-infarct area. MALDI-MS imaging showed the location-specific effect of cell therapies even in this subacute setting after MCAO. These methodologies may be useful for further investigation of possible treatments for ischemic brain injury.

DOI： 10.1038/s41598-020-78930-x

Web of Science

PubMed

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

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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

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Autologous cord blood cell therapy for neonatal hypoxic-ischaemic encephalopathy: a pilot study for feasibility and safety. Reviewed International journal

Tsuji M, Sawada M, Watabe S, Sano H, Kanai M, Tanaka E, Ohnishi S, Sato Y, Sobajima H, Hamazaki T, Mori R, Oka A, Ichiba H, Hayakawa M, Kusuda S, Tamura M, Nabetani M, Shintaku H

Scientific reports   Vol. 10 ( 1 ) page： 4603 - 4603   2020.3

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Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. Preclinical studies show that the systemic administration of umbilical cord blood cells (UCBCs) is beneficial for neonatal HIE. We conducted a single-arm clinical study to examine the feasibility and safety of intravenous infusion of autologous UCBCs for newborns with HIE. When a neonate was born with severe asphyxia, the UCB was collected, volume-reduced, and divided into three doses. The processed UCB was infused at 12-24, 36-48, and 60-72 hours after the birth. The designed enrolment was six newborns. All six newborns received UCBC therapy strictly adhering to the study protocol together with therapeutic hypothermia. The physiological parameters and peripheral blood parameters did not change much between pre- and postinfusion. There were no serious adverse events that might be related to cell therapy. At 30 days of age, the six infants survived without circulatory or respiratory support. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants. This pilot study shows that autologous UCBC therapy is feasible and safe.

DOI： 10.1038/s41598-020-61311-9

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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

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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

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

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

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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

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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

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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

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Comparison of Clinical Characteristics of Human Metapneumovirus and Respiratory Syncytial Virus Infections in Hospitalized Young Children

Taniguchi Akinobu, Kawada Jun-ichi, Go Kiyotaka, Fujishiro Naozumi, Hosokawa Yosuke, Maki Yuki, Sugiyama Yuichiro, Suzuki Michio, Tsuji Takeshi, Hoshino Shin, Muramatsu Hideki, Kidokoro Hiroyuki, Kinoshita Fumie, Hirakawa Akihiro, Takahashi Yoshiyuki, Sato Yoshiaki, Natsume Jun, Nagoya Collaborative Clinical Research Team

Japanese Journal of Infectious Diseases   Vol. 72 ( 4 ) page： 237 - 242   2019.7

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<p>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.</p>

DOI： 10.7883/yoken.JJID.2018.480

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Factors related to survival discharge in trisomy 18: A retrospective multicenter study. Reviewed International journal

Eiko Kato, Yuma Kitase, Takashi Tachibana, Tetsuo Hattori, Akiko Saito, Yukako Muramatsu, Koji Takemoto, Hikaru Yamamoto, Seiji Hayashi, Ayako Yasuda, Yuichi Kato, Kuniko Ieda, Makoto Oshiro, Yoshiaki Sato, Masahiro Hayakawa

American journal of medical genetics. Part A   Vol. 179 ( 7 ) page： 1253 - 1259   2019.7

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Infants with trisomy 18 (T18) previously had a poor prognosis; however, the intensive care of these patients has markedly diversified the prognosis. We investigated the current situation of patients with T18, clarified factors for survival discharge, and surveyed actual home healthcare. A total of 117 patients with T18 admitted to nine institutions between 2000 and 2015 were retrospectively investigated. After excluding four patients whose outcomes were unclear, we divided 113 patients into two groups-the survival discharge group (n = 52) and the death discharge group (n = 61)-and compared maternal factors, perinatal factors, neonatal factors, and therapeutic factors between the groups. In addition, home healthcare, readmission, utilization of respite care and home nursing, and cause of death among the survival group were surveyed. Fifty-two (44%) patients with T18 survived at discharge and their 1-year survival rate was 29%. The survival group had a longer gestation period, larger physique, and longer survival time, compared to the death group. Independent factors associated with survival discharge were the absence of an extremely low birthweight infant (ELBWI), the absence of esophageal atresia and patent ductus arteriosus, and cardiovascular surgery. All surviving patients required some home healthcare. The most frequent cause of death was a respiratory disorder. We recommend discussing the treatment strategy with families in the presence of neonatologists or pediatric surgeons, who can explain differences in prognosis, based on the gestation period, birthweight, severity of cardiovascular disease, and cardiovascular surgery.

DOI： 10.1002/ajmg.a.61146

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

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

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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

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

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

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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

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Correction: Treatment with silver nitrate versus topical steroid treatment for umbilical granuloma: A non-inferiority randomized control trial. Reviewed International journal

Chikako Ogawa, Yoshiaki Sato, Chiyo Suzuki, Azusa Mano, Atsushi Tashiro, Takafumi Niwa, Sayako Hamazaki, Yoshihiro Tanahashi, Midori Suzumura, Satoshi Hayano, Masahiro Hayakawa, Takeshi Tsuji, Shin Hoshino, Yuichiro Sugiyama, Hiroyuki Kidokoro, Jun-Ichi Kawada, Hideki Muramatsu, Akihiro Hirakawa, Masahiko Ando, Jun Natsume, Seiji Kojima

PloS one   Vol. 14 ( 6 ) page： e0218205   2019

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[This corrects the article DOI: 10.1371/journal.pone.0192688.].

DOI： 10.1371/journal.pone.0218205

PubMed

Magnetic resonance spectroscopy in preterm infants: association with neurodevelopmental outcomes. Reviewed International journal

Reina Hyodo, Yoshiaki Sato, Miharu Ito, Yuichiro Sugiyama, Chikako Ogawa, Hisashi Kawai, Toshiki Nakane, Akiko Saito, Akihiro Hirakawa, Hiroyuki Kidokoro, Jun Natsume, Masahiro Hayakawa

Archives of disease in childhood. Fetal and neonatal edition   Vol. 103 ( 3 ) page： F238 - F244   2018.5

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OBJECTIVE: To compare magnetic resonance spectroscopy (MRS) metabolite ratios in preterm infants at term-equivalent age with those in term infants and to evaluate the association between MRS metabolites and neurodevelopmental outcomes at 18 months corrected age in preterm infants. DESIGN: We studied infants born at a gestational age <37 weeks and weighing <1500 g during 2009-2013 using MRS at term-equivalent age. Infants with major brain abnormalities were excluded. The ratios of N-acetylaspartate (NAA) to creatine (Cre), NAA to choline-containing compounds (Cho) and Cho to Cre in the frontal white matter and thalamus were measured using multivoxel point-resolved proton spectroscopy sequence. Neurodevelopmental outcomes were assessed at 18 months corrected age. RESULTS: Thirty-three preterm infants and 16 term infants were enrolled in this study. Preterm infants with normal development at 18 months showed significantly lower NAA/Cho ratios in the frontal white matter than term infants. There were no differences in the Cre/Cho ratios between preterm and term infants. At 18 months corrected age, 9 preterm infants with a mild developmental delay showed significantly lower NAA/Cho ratios in the thalamus than 24 preterm infants with normal development. CONCLUSIONS: Preterm infants at term-equivalent age showed reduced MRS metabolites (NAA/Cho) compared with term infants. Decreased NAA/Cho ratios in the thalamus were associated with neurodevelopmental delay at 18 months corrected age in preterm infants.

DOI： 10.1136/archdischild-2016-311403

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Successful Infant Pneumonectomy with Unilateral Pulmonary Artery Occlusion Test Reviewed

Kato Koji, Kato Taichi, Hayano Satoshi, Fukasawa Yoshie, Numaguchi Atsushi, Hattori Tetsuo, Saito Akiko, Sato Yoshiaki, Hayakawa Masahiro

International Heart Journal   Vol. 59 ( 1 ) page： 237 - 239   2018.1

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<p>The use of unilateral pulmonary artery occlusion (UPAO) test for the preoperative evaluation of pneumonectomy was reported in adult patients. On the contrary, in infants, no strategies have yet been recommended to predict hemodynamics after pneumonectomy, nor has use of the UPAO test been reported. We describe the first case of infant with abnormal pulmonary circulation in whom successful pneumonectomy was performed after preoperative evaluation using UPAO test. Right pneumonectomy was planned for an 8-month-old girl, because of decreased right pulmonary function, high risk of pneumothorax, and impaired left lung expansion due to overexpansion caused by severe left bronchial stenosis and bronchomalacia. However, she had also prolonged pulmonary hypertension and there was difficulty in accurate echocardiographic evaluation of its severity due to concomitant left pulmonary artery stenosis. Furthermore, contrast-enhanced computer tomography suggested a certain degree of right pulmonary venous flow, discordant with the result showing scarce right pulmonary flow in perfusion scintigraphy. Predicting postoperative hemodynamic changes was therefore considered difficult. To evaluate these concerns, we performed cardiac catheterization and UPAO test to simulate postoperative hemodynamics. Pulmonary arteriography showed decreased but significant right pulmonary arterial and venous flows. Measurements including pulmonary artery pressure and cardiac index showed no marked changes after occlusion. Based on UPAO test results, the operation was successfully performed and hemodynamics remained stable postoperatively. The UPAO test may be useful for infants with cardiopulmonary impairment to evaluate the tolerability of pneumonectomy.</p>

DOI： 10.1536/ihj.16-606

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Other Link： http://orcid.org/0000-0001-6320-9176

Treatment with silver nitrate versus topical steroid treatment for umbilical granuloma: A non-inferiority randomized control trial. Reviewed International journal

Chikako Ogawa, Yoshiaki Sato, Chiyo Suzuki, Azusa Mano, Atsushi Tashiro, Takafumi Niwa, Sayako Hamazaki, Yoshihiro Tanahashi, Midori Suzumura, Satoshi Hayano, Masahiro Hayakawa, Takeshi Tsuji, Shin Hoshino, Yuichiro Sugiyama, Hiroyuki Kidokoro, Jun-Ichi Kawada, Hideki Muramatsu, Akihiro Hirakawa, Masahiko Ando, Jun Natsume, Seiji Kojima

PloS one   Vol. 13 ( 2 ) page： e0192688   2018

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OBJECTIVE: The aim of this prospective multicenter randomized controlled trial was to compare the efficacy of silver nitrate cauterization against that of topical steroid ointment in the treatment of neonatal umbilical granuloma. METHODS: An open-label, non-inferiority randomized controlled trial was conducted from January 2013 to January 2016. The primary endpoint for the silver nitrate cauterization and topical steroid ointment groups was the healing rate after 2 weeks of treatment, applying a non-inferiority margin of 10%. The healing rate was evaluated until completion of 3 weeks of treatment. RESULTS: Participants comprised 207 neonates with newly diagnosed umbilical granuloma, randomized to receive silver nitrate cauterization (n = 104) or topical steroid ointment (n = 103). Healing rates after 2 weeks of treatment were 87.5% (91/104) in the silver nitrate cauterization and 82% (82/100) in the topical steroid ointment group group. The difference between groups was -5.5% (95% confidence interval, -19.1%, 8.4%), indicating that the non-inferiority criterion was not met. After 3 weeks of treatment, the healing rate with topical steroid ointment treatment was almost identical to that of silver nitrate cauterization (94/104 [90.4%] vs. 91/100 [91.0%]; 0.6% [-13.2 to 14.3]). No major complications occurred in either group. CONCLUSIONS: This study did not establish non-inferiority of topical steroid ointment treatment relative to silver nitrate cauterization, presumably due to lower healing rates than expected leading to an underpowered trial. However, considering that silver nitrate cauterization carries a distinct risk of chemical burns and that the overall efficacy of topical steroid ointment treatment is similar to that of silver nitrate cauterization, topical steroid ointment might be considered as a good alternative in the treatment of neonatal umbilical granuloma due to its safety and simplicity. To clarify non-inferiority, a larger study is needed.

DOI： 10.1371/journal.pone.0192688

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Other Link： http://orcid.org/0000-0001-6320-9176

Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice. Reviewed International journal

Emi Tanaka, Yuko Ogawa, Takeo Mukai, Yoshiaki Sato, Takashi Hamazaki, Tokiko Nagamura-Inoue, Mariko Harada-Shiba, Haruo Shintaku, Masahiro Tsuji

Frontiers in neurology   Vol. 9   page： 133 - 133   2018

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Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs) have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12), and low-dose (1 × 104) or high-dose (1 × 105) UC-MSCs were administered intravenously 48 h after the insult (P14). To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by modulating the microglial reaction in the peri-infarct cortex.

DOI： 10.3389/fneur.2018.00133

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Administration of Bone Marrow-Derived Mononuclear Cells Contributed to the Reduction of Hypoxic-Ischemic Brain Injury in Neonatal Rats. Reviewed International journal

Yoshiaki Sato, Kazuto Ueda, Taiki Kondo, Tetsuo Hattori, Alkisti Mikrogeorgiou, Yuichiro Sugiyama, Toshihiko Suzuki, Michiro Yamamoto, Hitoshi Hirata, Akihiro Hirakawa, Keiko Nakanishi, Masahiro Tsuji, Masahiro Hayakawa

Frontiers in neurology   Vol. 9   page： 987 - 987   2018

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Background/Objective: Perinatal hypoxic-ischemia (HI) causes neonatal death and permanent neurological deficits. Cell therapy using various cell sources has been recently identified as a novel therapy for perinatal HI. Among the available types of cell sources, bone marrow-derived mononuclear cells (BMMNCs) have unique features for clinical application. For example, stem cells can be collected after admission, thus enabling us to perform autologous transplantation. This study aimed to investigate whether the administration of BMMNCs ameliorated HI brain injury in a neonatal rat model. Methods: Seven-day-old rats underwent left carotid artery ligation and were exposed to 8% oxygen for 60 min. BMMNCs were collected from the femurs and tibias of juvenile rats using the Ficoll-Hypaque technique and injected intravenously 24 h after the insult (1 × 105 cells). Active caspase-3, as an apoptosis marker, and ED1, as an activated microglia/macrophage marker, were evaluated immunohistochemically 48 h after the insult (vehicle, n = 9; BMMNC, n = 10). Behavioral assessments using the rotarod treadmill, gait analysis, and active avoidance tests were initiated 3 weeks after the insult (sham, n = 9, vehicle, n = 8; BMMNC, n = 8). After these behavioral tests (6 weeks after the insult), we evaluated the volumes of their hippocampi, cortices, thalami, striata, and globus pallidus. Results: The mean cell densities of the sum of four parts that were positive for active caspase-3 significantly decreased in the BMMNC group (p < 0.05), whereas in the hippocampi, cortices, thalami, and striata cell densities decreased by 42, 60, 56, and 47%, respectively, although statistical significance was not attained. The number of ED1 positive cells for the sum of the four parts also significantly decreased in the BMMNC group compared to the vehicle group (p < 0.05), whereas in each of the four parts the decrease was 35, 39, 47, and 36%, respectively, although statistical significance was not attained. In gait analysis, the BMMNC normalized the contact area of the affected hind paw widened by HI. The volumes of the affected striata and globus pallidus were significantly larger in the BMMNC group than in the control group. Conclusion: These results indicated that the injection of BMMNCs ameliorated HI brain injury in a neonatal rat model.

DOI： 10.3389/fneur.2018.00987

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Ureteral dilatation detected in magnetic resonance imaging predicts vesicoureteral reflux in children with urinary tract infection. Reviewed International journal

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

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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

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Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cell, but not Adipose Tissue-Derived Stem Cell, Ameliorated the Neonatal Hypoxic-Ischemic Brain Injury by Changing Cerebral Inflammatory State in Rat. Reviewed International journal

Yuichiro Sugiyama, Yoshiaki Sato, Yuma Kitase, Toshihiko Suzuki, Taiki Kondo, Alkisti Mikrogeorgiou, Asuka Horinouchi, Shoichi Maruyama, Yoshie Shimoyama, Masahiro Tsuji, Satoshi Suzuki, Tokunori Yamamoto, Masahiro Hayakawa

Frontiers in neurology   Vol. 9   page： 757 - 757   2018

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Perinatal hypoxic-ischemic (HI) brain injury occurs in 1 in 1,000 live births and remains the main cause of neurological disability and death in term infants. Cytotherapy has recently emerged as a novel treatment for tissue injury. In particular, mesenchymal stem cells (MSCs) are thought to have therapeutic potential, but little is known about the differences according to their origin. In the current study, we investigated the therapeutic effects and safety of intravenous injection of allogeneic bone marrow-derived MSCs (BM-MSCs) and adipose-derived stem cells (ADSCs) in a rat model of HI brain injury. HI models were generated by ligating the left carotid artery of postnatal day 7 Wistar/ST rats and exposing them to 8% hypoxia for 60 min. Bone marrow and adipose tissue were harvested from adult green fluorescent protein transgenic Wistar rats, and cells were isolated and cultured to develop BM-MSCs and ADSCs. At passaging stages 2-3, 1 × 105 cells were intravenously injected into the external right jugular vein of the HI rats at 4 or 24 h after hypoxia. Brain damage was evaluated by counting the number of cells positive for active caspase-3 in the entire dentate gyrus. Microglial isotypes and serum cytokines/chemokines were also evaluated. Distribution of each cell type after intravenous injection was investigated pathologically and bio-optically by ex vivo imaging (IVIS®) with a fluorescent lipophilic tracer DiR. The mortality rate was higher in the ADSC group compared to the BM-MSC group, in pups injected with cells 4 h after hypoxia. The number of active caspase-3-positive cells significantly decreased in the BM-MSC group, and the percentage of M1 microglia (a proinflammatory isotype) was also lower in the BM-MSC vs control group in the penumbra of the cortex. Moreover, BM-MSC administration increased anti-inflammatory cytokine and growth factor levels, while ADSCs did not. Each injected cell type was mainly distributed in the lungs and liver, but ADSCs remained in the lungs longer. Pathologically, pulmonary embolisms and diffuse alveolar hemorrhages were seen in the ADSC group. These results indicated that injection of allogeneic BM-MSCs ameliorated neonatal HI brain injury, whereas ADSCs induced severe lung hemorrhage and higher mortality.

DOI： 10.3389/fneur.2018.00757

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Grafting Neural Stem and Progenitor Cells Into the Hippocampus of Juvenile, Irradiated Mice Normalizes Behavior Deficits. Reviewed International journal

Yoshiaki Sato, Noriko Shinjyo, Machiko Sato, Marie K L Nilsson, Kazuhiro Osato, Changlian Zhu, Marcela Pekna, Hans G Kuhn, Klas Blomgren

Frontiers in neurology   Vol. 9   page： 715 - 715   2018

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The pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus of the hippocampus is reduced by ionizing radiation. This explains, at least partly, the learning deficits observed in patients after radiotherapy, particularly in pediatric cases. An 8 Gy single irradiation dose was delivered to the whole brains of postnatal day 9 (P9) C57BL/6 mice, and BrdU-labeled, syngeneic NSPCs (1.0 × 105 cells/injection) were grafted into each hippocampus on P21. Three months later, behavior tests were performed. Irradiation impaired novelty-induced exploration, place learning, reversal learning, and sugar preference, and it altered the movement pattern. Grafting of NSPCs ameliorated or even normalized the observed deficits. Less than 4% of grafted cells survived and were found in the dentate gyrus 5 months later. The irradiation-induced loss of endogenous, undifferentiated NSPCs in the dentate gyrus was completely restored by grafted NSPCs in the dorsal, but not the ventral, blade. The grafted NSPCs did not exert appreciable effects on the endogenous NSPCs; however, more than half of the grafted NSPCs differentiated. These results point to novel strategies aimed at ameliorating the debilitating late effects of cranial radiotherapy, particularly in children.

DOI： 10.3389/fneur.2018.00715

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Carbamylated Erythropoietin Decreased Proliferation and Neurogenesis in the Subventricular Zone, but Not the Dentate Gyrus, After Irradiation to the Developing Rat Brain. Reviewed International journal

Kazuhiro Osato, Yoshiaki Sato, Akari Osato, Machiko Sato, Changlian Zhu, Marcel Leist, Hans G Kuhn, Klas Blomgren

Frontiers in neurology   Vol. 9   page： 738 - 738   2018

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Cranial radiotherapy for pediatric brain tumors causes progressive, debilitating late effects, including cognitive decline. Erythropoietin (EPO) has been shown to be neuroprotective and to promote neuroregeneration. Carbamylated erythropoietin (CEPO) retains the protective properties of EPO but is not erythrogenic. To study the effects of CEPO on the developing brain exposed to radiotherapy, a single irradiation (IR) dose of 6 Gy was administered to the brains of postnatal day 9 (P9) rats, and CEPO (40 μg/kg s.c.) was injected on P8, P9, P11, P13, and P15. To examine proliferation, 5-Bromo-2-deoxyuridine (BrdU) was injected on P15, P16, and P17. CEPO administration did not affect BrdU incorporation in the granule cell layer (GCL) of the hippocampus or in the subventricular zone (SVZ) as quantified 7 days after the last BrdU injection, whereas IR decreased BrdU incorporation in the GCL and SVZ by 63% and 18%, respectively. CEPO did not affect BrdU incorporation in the GCL of irradiated brains, although it was reduced even further (to 31%) in the SVZ. To evaluate the effect of CEPO on neurogenesis, BrdU/doublecortin double-positive cells were quantified. CEPO did not affect neurogenesis in non-irradiated brains, whereas IR decreased neurogenesis by 58% in the dentate gyrus (DG) but did not affect it in the SVZ. In the DG, CEPO did not affect the rate of neurogenesis following IR, whereas in the SVZ, the rate decreased by 30% following IR compared with the rate in vehicle-treated rats. Neither CEPO nor IR changed the number of microglia. In summary, CEPO did not promote neurogenesis in non-irradiated or irradiated rat brains and even aggravated the decreased neurogenesis in the SVZ. This raises concerns regarding the use of EPO-related compounds following radiotherapy.

DOI： 10.3389/fneur.2018.00738

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Factors related to home health-care transition in trisomy 13. Reviewed International journal

Yuma Kitase, Masahiro Hayakawa, Taiki Kondo, Akiko Saito, Takashi Tachibana, Makoto Oshiro, Kuniko Ieda, Eiko Kato, Yuichi Kato, Tetsuo Hattori, Seiji Hayashi, Masatoki Ito, Reina Hyodo, Yukako Muramatsu, Yoshiaki Sato

American journal of medical genetics. Part A   Vol. 173 ( 10 ) page： 2635 - 2640   2017.10

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Trisomy 13 (T13) is accompanied by severe complications, and it can be challenging to achieve long-term survival without aggressive treatment. However, recently, some patients with T13 have been receiving home care. We conducted this study to investigate factors related to home health-care transition for patients with T13.We studied 28 patients with T13 born between January 2000 and December 2014. We retrospectively compared nine home care transition patients (the home care group) and 19 patients that died during hospitalization (the discharge at death group). The median gestational age of the patients was 36.6 weeks, with a median birth weight of 2,047 g. Currently, three patients (11%) have survived, and 25 (89%) have died. The home care group exhibited a significantly longer gestational age (38.9 vs. 36.3 weeks, p = 0.039) and significantly larger occipitofrontal circumference Z score (-0.04 vs. -0.09, p = 0.019). Congenital heart defects (CHD) was more frequent in the discharge at death group, with six patients in the home care group and 18 patients in the discharge at death group (67% vs. 95%, p = 0.047), respectively. Survival time was significantly longer in the home care group than in the discharge at death group (171 vs. 19 days, p = 0.012). This study has shown that gestational age, occipitofrontal circumference Z score at birth, and the presence of CHD are helpful prognostic factors for determining treatment strategy in patients with T13.

DOI： 10.1002/ajmg.a.38371

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Multilineage-differentiating stress enduring cellsを用いた新生児慢性肺疾患に対する新規治療法の開発 Invited

佐藤 義朗, 鈴木 俊彦, 田中 雅人, 上田 一仁, 田中 亮, 三浦 良介, 呉 尚治, 浅田 英之, 北瀬 悠磨, 立花 貴史, 見松 はるか, 伊藤 美香, 齊藤 明子, 村松 友佳子, 早川 昌弘, 出澤 真理, 串田 良祐

日本新生児成育医学会雑誌   Vol. 29 ( 3 ) page： 589 - 589   2017.10

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A new type of swaddling clothing improved development of preterm infants in neonatal intensive care units. Reviewed International journal

Yuma Kitase, Yoshiaki Sato, Hirokazu Takahashi, Misaki Shimizu, Chie Ishikawa, Hikaru Yamamoto, Masahiro Hayakawa

Early human development   Vol. 112   page： 25 - 28   2017.9

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BACKGROUND: Preterm infants undergo stress owing to essential treatments and exposure to the extrauterine environment in neonatal intensive care units. AIMS: The aim of this study was to enable preterm infants to maintain adequate positioning with a newly developed swaddling clothing, in order to improve low muscle tone and sleep quality, and to confirm the safety of the clothing. STUDY DESIGN: This prospective clinical trial included an intervention group (preterm infants wearing bag-shaped clothing, allowing only exposure of the head, n=27), and a control group (preterm infants managed only with conventional swaddling, n=12). OUTCOME MEASURES: We used the Dubowitz method to analyze behavior, recorded the frequency of vomiting and apnea in both groups, and assessed the sleep state in the intervention group. RESULTS: Muscle tone and total score for the Dubowitz method significantly improved in the intervention group, compared with those in the control group. We evaluated the sleep state before and after the introduction of the device in the intervention group, and State 1 increased from 53.5% to 69.2% after introduction. No significant difference was seen in the frequency of vomiting and apnea between the groups. CONCLUSIONS: The new swaddling clothing with enhanced stretch capacity improved the muscle tone and increased sleep time by decreasing the state level of preterm infants. This is an effective tool to assist in infant development in neonatal intensive care units.

DOI： 10.1016/j.earlhumdev.2017.06.005

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The relationship between three signs of fetal magnetic resonance imaging and severity of congenital diaphragmatic hernia Reviewed

T. Hattori, M. Hayakawa, M. Ito, Y. Sato, K. Tamakoshi, Y. Kanamorit, H. Okuyama, N. Inannura, S. Takahashi, Y. Fujino, T. Taguchi, N. Usui

JOURNAL OF PERINATOLOGY   Vol. 37 ( 3 ) page： 265 - 269   2017.3

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OBJECTIVE: To seek a simple approach for prenatally classifying congenital diaphragmatic hernia (CDH) severity using fetal magnetic resonance imaging (MRI) markers.
STUDY DESIGN: A retrospective, multicenter study using questionnaires to investigate fetal MRI findings. We included fetuses prenatally diagnosed with isolated left-sided CDH and delivered after 36 weeks of gestation. We focused on three fetal MRI morphological signs: incomplete pulmonary baseline (IPB), liver up (LU) and retrocardiac stomach (RCS). We also evaluated the fetal MRI score defined as the total number of positive signs; the primary outcome was survival at discharge.
RESULTS: In 256 patients (from 56 institutions), IPB, LU and RCS findings correlated with lower survival: odds ratio (95% confidence interval), 0.16 (0.08 to 0.33); 0.24 (0.12 to 0.51); and 0.14 (0.07 to 0.28); respectively. Patients with higher fetal MRI scores had a higher mortality rate.
CONCLUSION: IPB, LU and RCS on fetal MRI are related to CDH severity.

DOI： 10.1038/jp.2016.208

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Other Link： http://orcid.org/0000-0001-6320-9176

Rat umbilical cord blood cells attenuate hypoxic-ischemic brain injury in neonatal rats Reviewed

Nakanishi K, Sato Y, Mizutani Y, Ito M, Hirakawa A, Higashi Y.

Sci Rep   Vol. 7   page： 44111   2017

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DOI： 10.1038/srep44111

Dedifferentiated Fat Cells as a Novel Source for Cell Therapy to Target Neonatal Hypoxic-Ischemic Encephalopathy Reviewed

Alkisti Mikrogeorgiou, Yoshiaki Sato, Taiki Kondo, Tetsuo Hattori, Yuichiro Sugiyama, Miharu Ito, Akiko Saito, Keiko Nakanishi, Masahiro Tsuji, Tomohiko Kazama, Koichiro Kano, Taro Matsumoto, Masahiro Hayakawa

DEVELOPMENTAL NEUROSCIENCE   Vol. 39 ( 1-4 ) page： 273 - 286   2017

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

Neonatal hypoxic-ischemic (HI) encephalopathy (HIE) remains a major cause of mortality and persistent neurological disabilities in affected individuals. At present, hypothermia is considered to be the only applicable treatment option, although growing evidence suggests that cell-based therapy might achieve better outcomes. Dedifferentiated fat (DFAT) cells are derived from mature adipocytes via a dedifferentiation strategy called ceiling culture. Their abundance and ready availability might make them an ideal therapeutic tool for the treatment of HIE. In the present study, we aimed to determine whether the outcome of HIE can be improved by DFAT cell treatment. HI injury was achieved by ligating the left common carotid artery in 7-day-old rat pups, followed by 1-h exposure to 8% O-2. Subsequently, the severity of damage was assessed by diffusion-weighted magnetic resonance imaging to assign animals to equivalent groups. 24 h after hypoxia, DFAT cells were injected at 10(5) cells/pup into the right external jugular vein. To evaluate brain damage in the acute phase, a group of animals was sacrificed 48 h after the insult, and paraffin sections of the brain were stained to assess several acute injury markers. In the chronic phase, the behavioral outcome was measured by performing a series of behavioral tests. From the 24th day of age, the sensorimotor function was examined by evaluating the initial forepaw placement on a cylinder wall and the latency to falling from a rotarod treadmill. The cognitive function was tested with the novel object recognition (NOR) test. In vitro conditioned medium (CM) prepared from cultured DFAT cells was added at various concentrations to neuronal cell cultures, which were then exposed to oxygen-glucose deprivation (OGD). The number of cells that stained positive for the apoptosis marker active caspase-3 decreased by 73 and 52% in the hippocampus and temporal cortex areas of the brain, respectively, in the DFAT-treated pups. Similarly, the numbers of ED-1-positive cells (activated microglia) decreased by 66 and 44%, respectively, in the same areas in the DFAT-treated group. The number of cells positive for the oxidative stress marker 4-hydroxyl-2-nonenal decreased by 68 and 50% in the hippocampus and the parietal cortex areas, respectively, in the DFAT-treated group. The HI insult led to a motor deficit according to the rotarod treadmill and cylinder test, where it significantly affected the vehicle group, whereas no difference was confirmed between the DFAT and sham groups. However, the NOR test indicated no significant differences between any of the groups. DFAT treatment did not reduce the infarct volume, which was confirmed immunohistochemically. According to in vitro experiments, the cell death rates in the DFAT-CM-treated cells were significantly lower than those in the controls when DFAT-CM was added 48 h prior to OGD. The treatment effect of adding DFAT-CM 24 h prior to OGD was also significant. Our results indicate that intravenous injection with DFAT cells is effective for ameliorating HI brain injury, possibly via paracrine effects. (C) 2017 S. Karger AG, Basel

DOI： 10.1159/000455836

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Evaluations of Intravenous Administration of CD34+ Human Umbilical Cord Blood Cells in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy Reviewed

Ohshima M, Taguchi A, Sato Y, Ogawa Y, Saito S, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T, Tsuji M

Dev Neurosci   Vol. 38 ( 5 ) page： 331 - 341   2016

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DOI： 10.1159/000454830

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Abnormal urinalysis on day 7 in patients with IgA vasculitis (Henoch-Schonlein purpura) Reviewed

Kawashima N, Kawada J, Nishikado Y, Kitase Y, Ito S, Muramatsu H, Sato Y, Kato T, Natsume J, Kojima S.

Nagoya J Med Sci   Vol. 78 ( 4 ) page： 359-368   2016

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DOI： 10.18999/nagjms.78.4.359

Mild intrauterine hypoperfusion reproduces neurodevelopmental disorders observed in prematurity Reviewed

Ohshima M, Coq JO, Otani K, Hattori Y, Ogawa Y, Sato Y, Harada-Shiba M, Ihara M, Tsuji M.

Sci Rep   Vol. 6   page： 39377   2016

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DOI： 10.1038/srep39377

TREC定量による重症複合免疫不全症の新生児マススクリーニング Reviewed

小島大英、杉山裕一朗、村松秀城、近藤大貴、安井正宏、木戸真二、佐藤義朗、早川昌弘、小島勢二

日本小児科学会雑誌   Vol. 120 ( 10 ) page： 1462-1467   2016

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Multicenter observational study comparing sedation/analgesia protocols for laser photocoagulation treatment of retinopathy of prematurity Reviewed

Sato Y, Oshiro M, Takemoto K, Hosono H, Saito A, Kondo T, Aizu K, Matsusawa M, Futamura Y, Asami T, Terasaki H, Hayakawa M.

J Perinatol   Vol. 35 ( 11 ) page： 965-9   2015

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/jp.2015.112

Buckling surgery and supplemental intravitreal bevacizumab or photocoagulation on stage 4 retinopathy of prematurity eyes Reviewed

Futamura Y, Asami T, Nonobe N, Kachi S, Ito Y, Sato Y, Hayakawa M, Terasaki H.

Jpn J Ophthalmol   Vol. 59 ( 6 ) page： 378-88   2015

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DOI： 10.1007/s10384-015-0401-5

Administration of umbilical cord blood cells transiently decreased hypoxic-ischemic brain injury in neonatal rats Reviewed

Hattori T*, Sato Y*(*equally contribution), Kondo T, Ichinohashi Y, Sugiyama Y, Yamamoto M, Kotani T., Hirata H, Hirakawa A, Suzuki S, Tsuji M, Ikeda T, Nakanishi K, Kojima S, Blomgren K, Hayakawa M.

Dev Neurosci   Vol. 37 ( 2 ) page： 95-104   2015

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DOI： 10.1159/000368396

Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury Reviewed

Hattori Y, Kotani T, Tsuda H, Mano Y, Tu L, Li H, Hirako S, Ushida T, Imai K, Nakano T, Sato Y, Miki R, Sumigama S, Iwase A, Toyokuni S, Kikkawa F.

Free Radic Res   Vol. 49 ( 8 ) page： 1026-37   2015

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DOI： 10.3109/10715762.2015.1038257

Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury Reviewed

Nakano T, Kotani T, Mano Y, Tsuda H, Imai K, Ushida T, Li H, Miki R, Sumigama S, Sato Y, Iwase A, Hirakawa A, Asai M, Toyokuni S, Kikkawa F.

J Clin Biochem Nutr   Vol. 57 ( 3 ) page： 178-82   2015

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DOI： 10.3164/jcbn.15-90

Intraperitoneal and intravenous deliveries are not comparable in terms of drug efficacy and cell distribution in neonatal mice with hypoxia-ischemia Reviewed

Ohshima M, Taguchi A, Tsuda H, Sato Y, Yamahara K, Harada-Shiba M, Miyazato M, Ikeda T, Iida H, Tsuji M.

Brain Dev   Vol. 37 ( 4 ) page： 376-86   2015

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DOI： 10.1016/j.braindev.2014.06.010

Paradoxical downward seizure pattern on amplitude-integrated electroencephalogram Reviewed

Ito M, Kidokoro H, Sugiyama Y, Sato Y, Natsume J, Watanabe K, Hayakawa M.

J Perinatol   Vol. 34 ( 8 ) page： 642-4   2014

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Effects of intravenous administration of umbilical cord blood CD34 cells in a mouse model of neonatal stroke Reviewed

Tsuji M. Taguchi A, Ohshima M, Kasahara Y, Sato Y, Tsuda H, Otani K, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T.

Neuroscience   Vol. 263C   page： 148-158   2014

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Effect of placenta previa on neonatal respiratory disorders and amniotic lamellar body counts at 36-38weeks of gestation Reviewed

Tsuda H, Kotani T, Sumigama S, Mano Y, Hua L, Hayakawa H, Hayakawa M, Sato Y, Kikkawa F.

Early Hum Dev   Vol. 90 ( 1 ) page： 51-4   2014

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Astroglial IFITM3 mediates neuronal impairments following neonatal immune challenge in mice. Reviewed

Ibi D, Nagai T, Nakajima A, Mizoguchi H, Kawase T, Tsuboi D, Kano S, Sato Y, Hayakawa M, Lange UC, Adams DJ, Surani MA, Satoh T, Sawa A, Kaibuchi K, Nabeshima T, Yamada K.

Glia   Vol. 61 ( 5 ) page： 679   2013

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DOI： 10.1002/glia.22461

Amniotic lamellar body count and congenital diaphragmatic hernia in humans and in a rat model Reviewed

Watanabe Y, Tsuda H, Kotani T, Sumigama S, Mano Y, Hayakawa M, Sato Y, Kikkawa F.

Pediatr Res   Vol. 73 ( 3 ) page： 344-8   2013

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Grafting of neural stem and progenitor cells to the hippocampus of young, irradiated mice causes gliosis and disrupts the granule cell layer Reviewed

Sato Y, Shinjyo N, Sato M, Osato K, Zhu C, Pekna M, Kuhn HG, Blomgren K.

Cell Death Dis   Vol. 4   page： e591   2013

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The diameter of the inferior vena cava provides a noninvasive way of calculating central venous pressure in neonates Reviewed

Sato Y, Kawataki M, Hirakawa A, Toyoshima K, Kato T, Itani Y, Hayakawa M.

Acta Paediatr   Vol. 102 ( 6 ) page： e241-6   2013

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Dexamethasone administration to the neonatal rat results in neurological dysfunction at the juvenile stage even at low doses Reviewed

Ichinohashi Y, Sato Y, Saito A, Ito M, Watanabe K, Hayakawa M, Nakanishi K, Wakatsuki A, Oohira A.

Early Hum Dev   Vol. 89 ( 5 ) page： 283-8   2013

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A highly-sulfated chondroitin sulfate, CS-E, adsorbs specifically to neurons with nuclear condensation. Reviewed

Nakanishi K, Ito M, Sato Y, Oohira A.

Neuroscience research   Vol. 74   page： 223-239   2012

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DOI： 10.1016/j.neures.2012.08.009

Congenital pancreatoblastoma associated with beta-catenin mutation Reviewed

Ismael O, Shimada A, Hama A, Takahashi Y, Sato Y, Hayakawa M, Tsuchiya H, Tainaka T, Ono Y, Kaneko K, Ando H, Sato K, Kojima S.

Pediatric blood & cancer.   Vol. 58 ( 5 ) page： 827   2012

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Carbohydrate and energy metabolism in the brain of rats with thromboxane A2-induced fetal growth restriction. Reviewed

Hayakawa M, Sato Y, Hattori T, Ichinohashi Y, Nakayama A, Yamamoto H, Hemmi H, Ito M, Ieda K, Kojima S.

Pediatr Res.   Vol. 70 ( 1 ) page： 21-4   2011

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Biological activities of highly sulfated chondroitin sulfate polysaccharides on neural cells. Reviewed

Nakanishi K, Sato Y, Oohira A.

Research Advances in Neurochemistry, Global Research Network   Vol. 1   page： 1-10   2010

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The diffusion weighted imaging for an early diagnosis of parasagittal injury Reviewed

Tagaya M, Sato Y, Hayakawa M.

Pediatr Int.   Vol. 52 ( 2 ) page： 298-301   2010

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Apoptosis-inducing factor deficiency decreases the proliferation rate and protects the subventricular zone against ionizing radiation Reviewed

Osato, K.*Sato, Y.*(*equally contribution)Ochiishi,T.Osato, A.Zhu, C.Sato, M.Swanpalmer, J.Modjtahedi, N.Kroemer, G.Kuhn, H. G.Blomgren, K.

Cell Death & Disease   Vol. 1   page： e84   2010

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*Chondroitin Sulfate, a Major Niche Substance of Neural Stem Cells, and Cell Transplantation Therapy of Neurodegeneration Combined with Niche Modification. Invited Reviewed

Sato Y, Oohira A.

Curr Stem Cell Res Ther   Vol. 4 ( 3 ) page： 200-209   2009

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Male gender is related to the development of parenteral nutrition-associated cholestasis in neonates Reviewed

Takemoto K, Nakayama A, Ito M, Sato Y, Saito A, Tori Y, Kaneko K, Ando H, Hayakawa M.

Journal of Neonatal-Perinatal Medicine   Vol. 2 ( 4 ) page： 247-251   2009

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Behavioral abnormalities of fetal growth retardation model rats with reduced amounts of brain proteoglycans. Reviewed

Saito A, Matsui F, Hayashi K, Watanabe K, Ichinohashi Y, Sato Y, Hayakawa M, Kojima S, Oohira A.

Exp Neurol   Vol. 219 ( 1 ) page： 81-92   2009

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A highly sulfated chondroitin sulfate preparation, CS-E, prevents excitatory amino acid-induced neuronal cell death. Reviewed

Sato Y, Nakanishi K, Tokita Y, Kakizawa H, Ida M, Maeda H, Matsui F, Aono S, Saito A, Kuroda Y, Hayakawa M, Kojima S, Oohira A.

J Neurochem   Vol. 104   page： 1565-1576   2008

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Delayed neurological signs following isolated parasagittal injury in asphyxia at term. Reviewed

Sato Y, Hayakawa M, Iwata O, Okumura A, Kato T, Hayakawa F, Kubota T, Maruyama K, Hasegawa M, Sato M, Oshiro M, Kito O, Kojima S.

Eur J Paediatr Neurol   Vol. 12 ( 5 ) page： 359-365   2008

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Reduction of brain injury in neonatal hypoxic-ischemic rats by intracerebroventricular injection of neural stem/progenitor cells together with chondroitinase ABC. Reviewed

Sato Y, Nakanishi K, Hayakawa M, Kakizawa H, Saito A, Kuroda Y, Ida M, Tokita Y, Aono S, Matsui F, Kojima S, Oohira A.

Reprod Sci   Vol. 15 ( 6 ) page： 613-620   2008

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A new method of blood sampling reduces pain for newborn infants: a prospective, randomized controlled clinical trial. Reviewed

Sato Y, Fukasawa T, Hayakawa M, Yatsuya H, Hatakeyama M, Ogawa A, Kuno K.

Early Hum Dev   Vol. 83   page： 389-394   2007

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Novel SLC12A1 (NKCC2) mutations in two families with Bartter syndrome type 1. Reviewed

Adachi M, Asakura Y, Sato Y, Tajima T, Nakajima T, Yamamoto T, Fujieda K.

Endocr J   Vol. 54   page： 1003-1007   2007

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The MRI findings of the right-sided fetal lung can be used to predict postnatal mortality and the requirement for extracorporeal membrane oxygenation in isolated left-sided congenital diaphragmatic hernia. Reviewed

Hayakawa M, Seo T, Itakua A, Hayashi S, Miyauchi M, Sato Y, Saito A, Nakayama A, Takemoto K, Hasegawa M, Kaneko K, Okada M, Hayakawa H, Sumigama S, Kikkawa F, Ando H, Kojima S.

Pediatr Res   Vol. 62   page： 93-97   2007

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Neuroprotective effect of nipradilol, an NO donor, on hypoxic-ischemic brain injury of neonatal rats. Reviewed

Kakizawa H, Matsui F, Tokita Y, Hirano K, Ida M, Nakanishi K, Watanabe M, Sato Y, Okumura A, Kojima S, Oohira A.

Early Hum Dev   Vol. 83   page： 535-540   2007

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Magnetic resonance imaging regional T1 abnormalities at term accurately predict motor outcome in preterm infants. Reviewed

Nanba Y, Matsui K, Aida N, Sato Y, Toyoshima K, Kawataki M, Hoshino R, Ohyama M, Itani Y, Goto A, Oka A.

Pediatrics   Vol. 120   page： e10-e19   2007

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An animal model of intrauterine growth retardation induced by synthetic thromboxane a(2). Reviewed

Hayakawa M, Takemoto K, Nakayama A, Saito A, Sato Y, Hasegawa M, Ieda K, Mimura S.

J Soc Gynecol Investig   Vol. 13   page： 566-572   2006

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脳室周囲白質軟化症の発症頻度と胎児発育の関係 Reviewed

佐藤義朗, 松井潔, 難波由喜子, 猪谷泰史, 山中美智子

日本周産期・新生児医学会雑誌   Vol. 41 ( 1 ) page： 2000   2005

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Hypoxic ischemic encephalopathy associated with neonatal seizures without other neurological abnormalities. Reviewed

Sato Y, Okumura A, Kato T, Hayakawa F, Kuno K, Watanabe K.

Brain Dev   Vol. 25   page： 215-219   2003

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新しい奇形症候群父性片親ダイソミー14(paternal UPD14) Reviewed

黒澤健司、五十嵐葉子、佐藤義朗、星野陸夫、山中美智子、西村玄

こども医療センター医学誌   Vol. 32 ( 3 ) page： 123-125   2003

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胎児期より管理した新生児Bartter syndromeの1例 Reviewed

佐藤義朗、菅原智香、難波由喜子、豊島勝昭、松井潔、星野陸夫、大山牧子、川滝元良、山中美智子、猪谷泰史、後藤彰子

日本新生児学会雑誌   Vol. 39 ( 1 ) page： 52-57   2003

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Paternal UPD14 is responsible for a distinctive malformation complex. Reviewed

Kurosawa K, Sasaki H, Sato Y, Yamanaka M, Shimizu M, Ito Y, Okuyama T, Matsuo M, Imaizumi K, Kuroki Y, Nishimura G.

Am J Med Genet   Vol. 110   page： 268-272   2002

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極低出生体重児における左室壁応力・心筋短縮速度の経時的変化と肺出血・脳室内出血・脳室周囲白質軟化症の関連性について Reviewed

豊島勝昭、川滝元良、佐藤義朗、難波由喜子、松井潔、星野陸夫、大山牧子、猪谷泰史、後藤彰子、康井制洋、中澤誠

日本未熟児新生児学会雑誌   Vol. 14 ( 2 ) page： 45-52   2002

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Hypocarbia in preterm infants with periventricular leukomalacia: the relation between hypocarbia and mechanical ventilation. Reviewed

Okumura A, Hayakawa F, Kato T, Itomi K, Maruyama K, Ishihara N, Kubota T, Suzuki M, Sato Y, Kuno K, Watanabe K.

Pediatrics   Vol. 107   page： 469-475   2001

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小児呼吸器感染症における肺炎クラミジアの関与 Reviewed

宮島雄二、佐藤義朗、鈴木基正、石原尚子、久保田哲夫、加藤徹、山本光章、小川昭正、久野邦義

日本小児科学会雑誌.   Vol. 104 ( 3 ) page： 351-356   2000

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小児の肺炎クラミジア感染症と肺炎マイコプラズマ感染症の比較検討 Reviewed

宮島雄二、城所博之、佐藤義朗、鈴木基正、久保田哲夫、加藤徹、山本光章、小川昭正、久野邦義

日本小児科学会雑誌.   Vol. 104 ( 7 ) page： 723-729   2000

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