Faculty Profiles - SATO, Yoshiaki

Papers - SATO, Yoshiaki

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone.

DOI： 10.1016/j.jcyt.2020.01.009

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

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

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

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

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

Recently, cell therapy has been developed as a novel treatment for perinatal hypoxic-ischemic encephalopathy (HIE), which is an important cause of neurological disorder and death, and stem cells from human exfoliated deciduous teeth (SHED) express early markers for mesenchymal and neuroectodermal stem cells. We investigated the treatment effect of SHED for HIE in neonatal rats. Seven-day-old rats underwent ligation of the left carotid artery and were exposed to 8% hypoxic treatment. SHED (1 × 105 cells) were injected via the right external jugular vein 24 h after the insult. The effect of intravenous administration of SHED cells was evaluated neurologically and pathophysiologically. In the evaluation of engraftment using quantum dots 655, only a few SHED were detected in the injured cortex. In the immunohistological evaluation 24 h after injection, the numbers of positive cells of active caspase-3 and anti-4 hydroxynonenal antiserum were lower in the SHED group than in the vehicle group. The number of Iba-1+ cells in the cortex was higher in the SHED group. However, the proportion of M1 microglia (Iba-1+/ED-1+) was significantly decreased, whereas M2 microglia (Iba-1+/CD206+) tended to increase in the SHED group. In the behavioral tests performed 5 months after hypoxic treatment, compared to the vehicle group, the SHED group showed significant elongation of the endurance time in the rotarod treadmill test, significantly ameliorated proportion of using the impaired hand in the cylinder test, significantly lower ratio of right/left front paw area in gait analysis, and significantly higher avoidance rate in the active avoidance test. In the in vitro experiment with cultured neurons exposed to oxygen-glucose deprivation, we confirmed the neuroprotective effect of the condition medium of SHED. These results suggested that intravenous administration of SHED exerted a treatment effect both histologically and functionally, possibly via a paracrine effect.

DOI： 10.1089/scd.2019.0221

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

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

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

DOI： 10.3389/fncel.2020.00212

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

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

BACKGROUND: Many small for gestational age (SGA) infants have catch-up growth during the first 2 years of life, but approximately 10% have no catch-up growth, and short stature continues into adulthood. Identification of risk factors for absence of catch-up growth at an early age may be useful for earlier diagnosis and earlier treatment. METHODS: This was a retrospective multicenter study. The subjects were SGA infants with very low-birthweight (VLBW), who were followed up until the age of 3 years. The risk factors for absence of catch-up growth were identified on statistical analysis. RESULTS: Of the 217 SGA infants in this study, 181 were in the catch-up group and 36 were in the no catch-up group. The catch-up rate was 83%. On multivariate analysis adjusted for gestational age, birthweight, birth height, and birth head circumference, multipara, Z and ΔZ scores of length at 12 months of corrected age, and the Z score of height at 24 months of corrected age were risk factors for lack of catch-up at 3 years. CONCLUSIONS: The length Z and ΔZ scores at 12 months of corrected age may be useful for an earlier diagnosis and earlier initiation of growth hormone treatment in VLBW infants.

DOI： 10.1111/ped.13939

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

Language：English Publishing type：Research paper (scientific journal) Publisher：National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee

<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

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

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

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

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

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

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

DOI： 10.18999/nagjms.81.2.227

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

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

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

DOI： 10.1016/j.jiac.2019.01.003

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

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

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

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：International Heart Journal Association

<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

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

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