論文 - 桂木 真司
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Maternal Death Due to Pulmonary Arterial Hypertension ― A Nationwide Survey in Japan ― 査読あり
Aoki-Kamiya C., Katsuragi S., Shiina Y., Hasegawa J., Yoshimatsu J., Nakai A., Ishiwata I., Sekizawa A., Ikeda T.
Circulation Journal 89 ( 1 ) 77 - 82 2024年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation Journal
Background: With advances in treatment, the prognosis for pregnancies complicated by pulmonary arterial hypertension (PAH) has been improving. However, PAH-related maternal mortality remains high compared with that due to other cardiovascular diseases. The specifics of PAH-related maternal deaths under advanced medical standards are not well understood. Methods and Results: We used the maternal death registration system established by the Japan Association of Obstetricians and Gynecologists and reviewed 6 PAH-related maternal deaths from 2010 to 2022. All women were initially diagnosed with PAH during pregnancy or immediately after childbirth. The diagnosis of PAH tended to be delayed because symptoms were not reported to healthcare providers and/or a different disease was diagnosed. Cardiogenic shock occurred antepartum in 1 woman and during delivery or within 7 days after delivery in the other 5 women. Four women were resuscitated and started on extracorporeal membrane oxygenation. Pulmonary vasodilators were initiated in 4 women, with a median duration of 8 days from PAH diagnosis to starting medication. Right heart failure was the most common cause of maternal death, with a median duration of 16 days from PAH diagnosis to maternal death. Conclusions: All PAH-related maternal deaths occurred in women who were diagnosed with PAH after pregnancy. Diagnosing PAH and initiating pulmonary vasodilators takes considerable time, highlighting the importance of early diagnosis and early treatment.
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Tachycardia-Induced Cardiomyopathy Following Prolonged Ritodrine Infusion During Pregnancy: A Case Report. 査読あり
Nakao M, Izawa M, Takamisawa I, Horiuchi C, Ohmori A, Katsuragi S
Cureus 16 ( 12 ) e76465 2024年12月
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Out-of-pocket fertility preservation expenses: data from a Japanese nationwide multicenter survey 査読あり
Ono M., Takai Y., Harada M., Horie A., Dai Y., Kikuchi E., Miyachi M., Yamamoto T., Fujii N., Kajiyama H., Manabe A., Yasuoka T., Katsuragi S., Mekaru K., Maezawa T., Horage Y., Kataoka S., Nakayama R., Nakajima T.E., Kimura F., Shimizu C., Sugimoto K., Takae S., Yumura Y., Nishi H., Furui T., Morishige K.I., Watanabe C., Osuga Y., Suzuki N.
International Journal of Clinical Oncology 29 ( 12 ) 1959 - 1966 2024年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Clinical Oncology
Background: The expenses related to fertility preservation or subsequent assisted reproductive treatments are significant for adolescents and young adult patients in Japan’s current healthcare system. With fertility preservation becoming more widespread in developed countries, it is expected that these costs will be covered by insurance or subsidies. It is critical for patients, healthcare providers, and the government to know the costs that patients will be responsible for. In Japan, the costs of fertility preservation and subsequent assisted reproductive technology are not covered by insurance, but patients can apply for subsidies from the local and central governments if certain conditions are met. Presently, the above-mentioned costs, as well as the amount paid by the patient, vary by facility. Therefore, it is essential to ensure patients’ continued access to necessary medical care despite the associated costs. Methods: In this study, questionnaires were mailed to 186 certified fertility preservation facilities in Japan to assess patients who had undergone fertility preservation or assisted reproduction. The questionnaires were sent between October 27, 2023 and March 31, 2024, with 140 of the 186 facilities responding (response rate: 75.3%). Results: Our findings show that approximately one-third of the costs was borne by the patients. Conclusion: Given these circumstances, sustainable pricing and insurance coverage are necessary for both patients and facilities.
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Hasegawa J., Sekizawa A., Tanaka H., Katsuragi S., Tanaka K., Nakata M., Hayata E., Murakoshi T., Ishiwata I., Ikeda T.
International Journal of Infectious Diseases 146 2024年9月
掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Infectious Diseases
Objectives: To clarify the infection route in maternal death due to invasive group A streptococcal (GAS) infection and toxic shock syndrome (TSS). Methods: A retrospective study was conducted on maternal deaths due to GAS-TSS in Japan between January 2010 and March 2024. The final causal diagnosis of maternal death and the infection routes of GAS were analysed using medical records, laboratory data and autopsy findings. Results: Among the 616 maternal deaths during the study period, 48 (8%) involved infectious diseases. The most common infection was invasive GAS (56%, n = 27), 21 (78%) and six cases occurred during the antepartum and puerperium periods, respectively. In the GAS-TSS group, 71% (15/21) infections were originated the upper respiratory tract. However, in the puerperium cases, 67% (4/6) were infected from the genital tract. In addition, no maternal deaths due to GAS-TSS were reported during the COVID-19 pandemic period in Japan from 2020 to 2023. Conclusion: Most antepartum GAS infections were from the upper respiratory tract. They may be reduced by preventive measures, including frequent disinfection, wearing masks and isolation from persons at high risk of carrying GAS, such as symptomatic children. On the other hand, GAS-TSS during puerperium infection via the genital tract.
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Relationship between maternal mortality and ritodrine hydrochloride as a tocolytic agent in Japan 査読あり
Nakamura M., Sekizawa A., Hasegawa J., Nakata M., Katsuragi S., Tanaka H., Murakoshi T., Kanayama N., Ishiwata I., Ikeda T.
The journal of obstetrics and gynaecology research 50 ( 7 ) 1111 - 1117 2024年7月
掲載種別：研究論文（学術雑誌） 出版者・発行元：The journal of obstetrics and gynaecology research
AIM: In Japan, unlike Western countries, tocolytic agents are administered in long-term protocols to treat threatened preterm labor. Evaluating the side effects of this practice is crucial. We examined whether ritodrine hydrochloride had been administered in cases of maternal death, aiming to investigate any relationship between ritodrine administration and maternal death. METHODS: This retrospective cohort study used reports of maternal deaths from multiple institutions in Japan between 2010 and 2020. Data on the reported cases were retrospectively analyzed, and data on the route of administration, administered dose, and clinical findings, including causes of maternal death, were extracted. The amount of tocolytic agents was compared between maternal deaths with ritodrine administration and those without. RESULTS: A total of 390 maternal deaths were reported to the Maternal Death Exploratory Committee in Japan during the study period. Ritodrine hydrochloride was administered in 32 of these cases. The frequencies (n) and median doses (range) of oral or intravenous ritodrine hydrochloride were 34.4% (11) and 945 (5-2100) mg and 84.4% (27) and 4032 (50-18 680) mg, respectively. Frequencies of perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema as causes of maternal death were significantly higher with ritodrine administration than without it. CONCLUSIONS: Our results suggest a relationship between long-term administration of ritodrine hydrochloride and an increased risk of maternal death due to perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema. In cases where ritodrine should be administered to prevent preterm labor, careful management and monitoring of maternal symptoms are required.
DOI： 10.1111/jog.15951
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看護学生における月経随伴症状に関する検討 査読あり
桂木真司
宮崎県医師会医学会誌 48 ( 1 ) 94 - 100 2024年3月
掲載種別：研究論文（学術雑誌）
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過去15年間の宮崎県の分娩数および分娩施設数に関する検討 査読あり
桂木真司
宮崎県医師会医学会誌 48 ( 1 ) 88 - 93 2024年3月
掲載種別：研究論文（学術雑誌）
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骨髄異型性症候群合併妊娠の管理 査読あり
桂木真司
宮崎県医師会医学会誌 48 ( 1 ) 113 - 116 2024年3月
担当区分：責任著者 掲載種別：症例報告
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Enomoto N., Maki S., Nii M., Yamaguchi M., Tamaishi Y., Takakura S., Magawa S., Tanaka K., Tanaka H., Kondo E., Katsuragi S., Ikeda T.
Scientific Reports 13 ( 1 ) 20945 2023年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Although digital examination of the cervix is the standard method used worldwide for evaluating the progress of delivery, it is subjective. Transperineal ultrasound (TPU) is combined with digital evaluation for accurate assessment of fetal descent and rotation of the advanced part of the fetus. This retrospective study aimed to clarify the impact of introducing TPU on perinatal outcomes at Mie University Hospital. We analyzed singleton pregnant women who underwent delivery management at our hospital between April 2020 and March 2021. Perinatal outcomes were compared between patients who used TPU (TPU+ group) and those who did not (TPU− group). The angle of progression and head direction were measured. The rate of vaginal delivery was significantly increased (90.9% vs. 71.6%; P = 0.0017), and the second stage of labor was significantly prolonged in the TPU+ group (148.1 vs. 75.8 min; P < 0.0001). A significant difference was observed in termination in the latent phase between the TPU+ group [3/8 (37.5%) cases] and TPU− group [20/25 (80.0%) cases] (P = 0.036). The rate of vaginal delivery can be increased through accurate evaluation of the progress of delivery with TPU.
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High maternal mortality rate associated with advanced maternal age in Japan
Tanaka H., Hasegawa J., Katsuragi S., Tanaka K., Arakaki T., Nakamura M., Hayata E., Nakata M., Murakoshi T., Sekizawa A., Ishiwata I., Ikeda T.
Scientific Reports 13 ( 1 ) 2023年12月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
This study aimed to clarify the relationship between maternal mortality and advanced maternal age in Japan and to provide useful information for future perinatal management. Maternal death rates by age group were investigated for all maternal deaths in Japan for an 11-year period, from 2010 to 2021. Maternal deaths among those aged ≥ 40 years were examined in detail to determine the cause, and the number of deaths by cause was calculated. The causes of onset of the most common causes of death were also investigated. The maternal mortality rates were 0.8 (95% confidence interval [CI] 0.3–4.7) for < 20 years, 2.6 (95% CI 1.7–3.8) for 20–24 years, 2.9 (95% CI 2.3–3.6) for 25–29 years, 3.9 (95% CI 3.3–4.5) for 30–34 years, 6.8 (95% CI 5.9–7.9) for 35–39 years, and 11.2 (95% CI 8.8–14.3) for ≥ 40 years of age. Patients who were ≥ 40 years of age had a significantly higher mortality rate compared to that in other age groups. Hemorrhagic stroke was the most common cause of death in patients aged ≥ 40 years (15/65 [23%]), and preeclampsia (8/15 [54%]) was the most common cause of hemorrhagic stroke. Maternal mortality is significantly higher in older than in younger pregnant women in Japan, with hemorrhagic stroke being the most common cause of maternal death among women > 40 years of age. More than half of hemorrhagic strokes are associated with hypertension disorder of pregnancy. These facts should be considered by women who become pregnant at an advanced age and by healthcare providers involved in their perinatal care.
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子宮頸癌放射線治療後の照射野内リンパ節再発に対して手術療法を選択した5例
藤﨑 碧, 大西 淳仁, 佐藤 謙成, 大澤 綾子, 圓﨑 夏美, 吉本 望, 川越 靖之, 永井 公洋, 桂木 真司
日本婦人科腫瘍学会雑誌 42 ( 3 ) 285 - 291 2023年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：公益社団法人 日本婦人科腫瘍学会
概要：子宮頸癌において初回治療で放射線照射歴のある症例では，再発した場合その場所が照射野内か照射野外かが治療法の選択ならびに予後に重要である．照射野内の再発部位への再照射は，合併症等から限定的であり，その他の有効な治療法が限られるため生存期間が短い．選択される治療法は化学療法が中心であり，近年では免疫チェックポイント阻害薬が有効な薬剤として注目されている．手術療法はあくまでも限定的であり，骨盤除臓術，salvage hysterectomy＋lymphadenectomyやsalvage lymphadenectomyなどが報告されている．骨盤除臓術はある程度の根治性は担保されるものの，患者への侵襲，機能損失が大きい術式であり，限られた症例にのみ適応となる．一方でsalvage hysterectomy＋lymphadenectomy，lymphadenectomyは報告例も少なく，根治性よりもQOLを重視した治療法といえる．今回われわれは，子宮頸癌の照射野内リンパ節再発に対して，腫瘍の摘出のみを目的とする外科的介入を行い，患者への侵襲を軽減しなおかつ良好な結果を得られた5症例を経験したので報告する．
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生後9ヶ月まで生存したThanatophoric dysplasiaの一例 査読あり
桂木真司
宮崎県医師会医学会誌 47 ( 2 ) 186 - 190 2023年9月
担当区分：責任著者 掲載種別：症例報告
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Effects of sturgeon fillet intake on top-ranked Japanese female long-distance runners
Haraguchi N., Nakao H., Sakakibara Y., Tamura H., Nagahama K., Sakurai K., Sameshima H., Schauerte M., Ikenoue T., Katsuragi S.
Journal of Obstetrics and Gynaecology Research 49 ( 8 ) 2164 - 2174 2023年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Obstetrics and Gynaecology Research
Aims: The aim of this study is to investigate whether consumption of sturgeon fillets reduces the oxidative stress marker urinary 8-hydroxy-2′-deoxyguanosine (8OHdG) in top-ranked Japanese female long-distance runners. Methods: In a before-and-after study, nine professional long-distance female athletes ate 100 g/day of sturgeon fillets for 2 weeks. Urinalysis (8OHdG, an oxidative stress marker, and creatinine), blood tests (fatty acids and 25-hydroxyvitamin D [25OHD]), exercise intensity, subjective fatigue, muscle elasticity, muscle mass, body fat mass, and nutritional intake using image-based dietary assessment (IBDA) were compared before, immediately after, and 1 month after the intervention. Results: Consumption of sturgeon fillets suppressed 8OHdG (p < 0.05) in the increased exercise intensity female athletes. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and 25OHD levels in blood increased from before to immediately after and 1 month after the intervention (p < 0.05). IBDA showed that intake of n-3 fatty acid increased after and one month after the intervention, whereas DHA, imidazole dipeptide and vitamin D intake increased after the intervention (p < 0.05) and then decreased after 1 month (p < 0.05). There were no significant changes in subjective fatigue, muscle elasticity, muscle mass, and body fat. Conclusions: The results suggest that eating sturgeon fillets during intense training may increase blood levels of EPA, DHA, and 25OHD, which may suppress urinary oxidative stress (8OHdG) in top-ranked Japanese long-distance runners.
DOI： 10.1111/jog.15711
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Tanaka H., Hasegawa J., Katsuragi S., Tanaka K., Arakaki T., Nakamura M., Hayata E., Nakata M., Sekizawa A., Ishiwata I., Ikeda T.
Journal of Clinical Medicine 12 ( 8 ) 2023年4月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Clinical Medicine
Background: Unlike Europe and the United States, Japan has seen numerous maternal deaths from hemorrhagic strokes related to hypertensive disorders of pregnancy (HDP). This study retrospectively analyzed deaths associated with HDP-related hemorrhagic stroke in Japan to determine the number of deaths that may have been prevented with blood pressure control during pregnancy. Methods: This study included maternal deaths related to hemorrhagic stroke cases. The proportion of patients without proteinuria whose blood pressure exceeded 140/90 mmHg between 14+0 and 33+6 weeks of gestation were determined. Lastly, the application of tight antihypertensive management was evaluated. Results: Among 34 HDP-related maternal deaths, 4 cases involved patients without proteinuria whose blood pressures exceeded 140/90 mmHg between 14+0 and 33+6 weeks of gestation. These included two chronic hypertension and two gestational hypertension cases. None of the patients received antihypertensive agents, and their blood pressures were managed leniently. Conclusion: Among HDP-related hemorrhagic stroke deaths in Japan, only a few cases of maternal death could have been prevented with tight blood pressure management, as described in the CHIPS randomized controlled trial. Therefore, to prevent HDP-related hemorrhagic stroke in Japan, new preventive strategies during pregnancy should be established.
DOI： 10.3390/jcm12082908
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特集 妊産婦死亡の現状と削減に向けた対策 総論 妊娠高血圧症候群に関連した死亡の削減に向けて
桂木 真司
周産期医学 53 ( 3 ) 287 - 293 2023年3月
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Miyoshi T., Maeno Y., Matsuda T., Ito Y., Inamura N., Kim K.S., Shiraishi I., Kurosaki K., Ikeda T., Sago H., Horigome H., Yoda H., Tsukahara S., Teramachi Y., Takahashi K., Toyoshima K., Nakai M., Katsuragi S.
Ultrasound in Obstetrics and Gynecology 61 ( 1 ) 49 - 58 2023年1月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Ultrasound in Obstetrics and Gynecology
Objectives: Although many studies have supported the efficacy of transplacental treatment for fetal supraventricular tachyarrhythmia, the long-term neurodevelopmental outcome after antenatal antiarrhythmic treatment is not well understood. The aim of this study was to investigate the prognosis and neurodevelopmental outcome at 36 months of corrected age and the incidence of tachyarrhythmia after birth, following protocol-defined antenatal therapy for fetal supraventricular tachyarrhythmia. Methods: This was a 3-year follow-up study of a multicenter trial that evaluated the efficacy and safety of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). The primary endpoints were mortality and neurodevelopmental impairment (NDI) at 36 months of corrected age. NDI was defined as any of the following outcomes: cerebral palsy, bilateral blindness, bilateral deafness or neurodevelopmental delay. Neurodevelopmental delay was evaluated using appropriate developmental quotient scales, mainly the Kyoto Scale of Psychological Development, or examination by pediatric neurologists. The detection rate of tachyarrhythmia at birth and at 18 and 36 months of corrected age was also evaluated as the secondary endpoint. In addition, the association of NDI at 36 months with perinatal and postnatal factors was analyzed. Results: Of 50 patients enrolled in the original trial, one withdrew consent and in two there was fetal death, leaving 47 patients available for enrollment in this follow-up study. Of these, 45 cases were available for analysis after two infants were lost to follow-up. The mortality rate was 2.2% (1/45) during a median follow-up of 3.2 (range, 2.1–9.4) years. The infant died at the age of 2.1 years. Another infant had missing neurodevelopmental assessment data. In the remaining 43 infants, at 36 months of corrected age, NDI was detected in 9.3% (4/43) overall and in two of three (66.7%) cases with fetal hydrops with subcutaneous edema. Cerebral palsy was noted in two infants with severe subcutaneous edema or ascites at an early gestational age. Neurodevelopmental delay was found in two infants with severe congenital abnormalities (one with tuberous sclerosis and the other with heterotaxy syndrome). Tachyarrhythmia was present in 31.9% (15/47) cases in the neonatal period and decreased to 8.9% (4/45) and 4.5% (2/44) at 18 and 36 months of corrected age, respectively. The median ventricular rate at diagnosis was significantly higher in infants with NDI compared to those without (265 vs 229 bpm; P = 0.003). In infants with NDI, compared to those without, fetal hydrops with subcutaneous edema at diagnosis was more common (50.0% vs 2.6%; P = 0.019) and the duration of fetal effusion was longer (median, 10.5 vs 0 days; P = 0.013). Postnatal arrhythmia and physical development abnormalities were not associated with NDI. Conclusions: This multicenter 3-year follow-up study is the first to demonstrate the long-term mortality and morbidity of infants born following protocol-defined transplacental treatment for fetal SVT and AFL. NDI was associated with the presence of fetal hydrops with subcutaneous edema at diagnosis and longer duration of fetal effusion. Neurodevelopmental delay was detected only in infants with severe congenital abnormalities. Therefore, in infants that have undergone antenatal treatment for fetal tachyarrhythmia and in which there are no comorbidities, the risk of NDI is low. However, in those with fetal hydrops with subcutaneous edema and/or associated severe congenital abnormalities, the risk for long-term neurologic morbidity might be considered somewhat increased. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
DOI： 10.1002/uog.26113
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ウレアプラズマ肺炎を契機に顕在化した超早産児肺リンパ管拡張症の一例 査読あり
榊原 康平, 山田 直史, 児玉 由紀, 小畑 静, 都築 康恵, 村岡 純輔, 青木 良則, 山下 理絵, 中目 和彦, 金子 政時, 桂木 真司, 都築 諒, 佐藤 勇一郎
日本周産期・新生児医学会雑誌 59 ( 1 ) 116 - 121 2023年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本周産期・新生児医学会
肺リンパ管拡張症（Pulmonary lymphangiectasia；PL）は肺リンパ管拡張を特徴とし，肺胞拡張障害をきたして重篤な呼吸不全を起こす疾患である．今回，ウレアプラズマ肺炎を契機に呼吸状態が増悪し，剖検でPLと診断された症例を報告する． 症例は超低出生体重児（在胎23週2日，610g，男児）．母体は，妊娠23週1日に胎胞形成，23週2日に経腟分娩となった．児はサーファクタント投与後，安定化した状態で人工呼吸管理を行っていた．日齢15にCRP上昇と肺野の透過性低下が認められた．各種抗菌薬治療では改善なく，日齢30の気管内分泌物ウレアプラズマ培養陽性により，アジスロマイシン水和物を開始した．CRPは著減したが，呼吸不全は悪化して日齢44に死亡した．病理解剖では，肺リンパ管がびまん性に拡張したPLと診断した．臨床的にはウレアプラズマ肺炎を契機に顕在化したPLと考えられた．
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Kawano T., Kawagoe Y., Fujisaki M., Osawa A., Ueno N., Enzaki N., Kawaguchi T., Onishi J., Katsuragi S., Sameshima H.
Internal Medicine 62 ( 4 ) 629 - 632 2023年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
We herein report a case of ovarian cancer recurrence detected every time with symptoms of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. A 46-year-old woman who had a history of ovarian cancer 9 months earlier developed joint pain along with pitting edema in both hands and was diagnosed with RS3PE syndrome. Two and four years after initial surgery for ovarian cancer, symptoms of RS3PE syndrome appeared, and a recurrent site was detected. With resection of the relapsed sites and increased maintenance dose of methylprednisolone, these symptoms improved within a month.
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Matsushita T., Arakaki T., Sekizawa A., Hasegawa J., Tanaka H., Katsuragi S., Nakata M., Murakoshi T., Ikeda T., Ishiwata I.
Journal of Maternal-Fetal and Neonatal Medicine 36 ( 1 ) 2175207 2023年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Objective: Cardiovascular disease (CVD) is the leading cause of maternal deaths in high-income countries. This study aimed to assess the characteristics of maternal deaths due to CVDs and the quality of care provided to patients, and to identify elements to improve maternal care in Japan. Methods: This descriptive study used the maternal death registration data of the Maternal Deaths Exploratory Committee of Japan between 2010 and 2019. Results: Of 445 eligible pregnancy-related maternal deaths, 44 (9.9%) were attributed to CVD. The most frequent cause was aortic dissection (18 patients, 40.9%), followed by peripartum cardiomyopathy (8 patients, 18.2%), and pulmonary hypertension (5 patients, 11.4%). In 31.8% of cases, cardiopulmonary arrest occurred within 30 min after initial symptoms. Frequent symptoms included pain (27.3%) and respiratory symptoms (27.3%), with 61.4% having initial symptoms during the prenatal period. 63.6% of the patients had known risk factors, with age ≥35 years (38.6％), hypertensive disorder (15.9%), and obesity (15.9%) being the most common. Quality of care was assessed as suboptimal in 16 (36.4%) patients. Cardiac risk assessment was insufficient in three patients with preexisting cardiac disease, while 13 patients had symptoms and risk factors warranting intensive monitoring and evaluation. Conclusion: Aortic dissection was the leading cause of maternal death due to CVDs. Obstetrics care providers need to be familiar with cardiac risk factors and clinical warning signs that may lead to impending fatal cardiac events. Timely risk assessment, patient awareness, and a multidisciplinary team approach are key to improving maternal care in Japan.
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特集 Controversies in perinatology 2023 産科編 妊娠中の巨大子宮筋腫合併-核出術を行わない
中山 徹男, 桂木 真司
周産期医学 52 ( 12 ) 1689 - 1691 2022年12月
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Tomimori-Gi K., Katsuragi S., Kodama Y., Yamada N., Sameshima H., Maekawa K., Yamashita A., Gi T., Sato Y.
Virchows Archiv 481 ( 5 ) 713 - 720 2022年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Virchows Archiv
Preeclampsia, a multisystem pregnancy-specific hypertensive disorder, results in significant maternal and perinatal morbidity and mortality. This condition is associated with placental histopathological abnormalities and particularly affects the decidual spiral arteries. Reportedly, aspirin prevents preeclampsia, specifically early-onset preeclampsia, although findings in decidual arteries in women treated with aspirin therapy remain unclear. We compared the clinical and histopathological placental findings between women with a history of preeclampsia, who did and did not receive low-dose aspirin therapy (LDA and non-LDA groups, respectively). We identified 26 women with a history of preeclampsia; 9 women received LDA (aspirin ≤ 100 mg/day, initiated at < 16 weeks, LDA group), and 17 women did not receive LDA (non-LDA group). The mean gestational age was higher (36.7 weeks vs. 32.3 weeks, P = 0.0221) and the incidence of preeclampsia was lower (11% vs. 59%, P = 0.0362) in the LDA than in the non-LDA group. Histopathologically, the incidence of decidual arteriopathy, particularly that of fibrinoid necrosis and thrombosis, was lower in the LDA than in the non-LDA group (44% vs. 88%, P = 0.0283). Immunohistologically, endothelial marker (CD31 and CD39) expression was stronger in the LDA than in the non-LDA group. Notably, we observed no significant intergroup differences in inflammatory changes (chronic perivasculitis, protease-activated receptor 1 expression, and CD3-positive cells). This study highlights that LDA inhibits hypertension-induced endothelial injury and thrombosis, and thereby protects maternal placental perfusion and prevents preeclampsia.
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Fetal distress and neonatal death after thoracoamniotid shunting therapy due to hydrops associated with transient abnormal myelopoiesis 査読あり
Shinji Katsuragi
Cureus 14 ( 9 ) 2022年9月
掲載種別：研究論文（学術雑誌）
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Fetal Distress and Neonatal Death After Thoracoamniotic Shunting Therapy Due to Hydrops Associated With Transient Abnormal Myelopoiesis.
Muraoka J, Yoshimoto N, Ohsawa A, Matsuzawa S, Katsuragi S
Cureus 14 ( 9 ) e28991 2022年9月
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Remitting seronegative symmetrical Synovitis with pitting edema syndrome as a manifestation of recurrent ovarian cancer: A case report 査読あり
Shinji Katsuragi
Internal Medicine 62 629 - 632 2022年8月
掲載種別：症例報告
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Low-dose aspirin therapy improves decidual arteriopathy in pregnant women with a history of preeclampsia 査読あり
Shinji Katsuragi
Virchows Archiv 481 713 - 720 2022年7月
掲載種別：研究論文（学術雑誌）
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Tomimori K., Kodama Y., Tanaka H., Yamashita A., Gi T., Asada Y., Doi K., Katsuragi S., Sato Y.
Virchows Archiv 480 ( 6 ) 1181 - 1187 2022年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Virchows Archiv
Transient abnormal myelopoiesis (TAM), also known as transient myeloproliferative disorder or transient leukemia, is a self-regressing neoplasia that afflicts infants with trisomy 21. A recent review article documented “myeloid cell thrombus (MCT)” and “fetal vascular malperfusion (FVM)” in placentas with TAM, although the characteristic TAM placental findings have not been clarified. Here, we compared the clinical and pathological placental findings between trisomy 21 patients with or without TAM. In 13 cases of trisomy 21, we identified six placentas with TAM and seven placentas without TAM. The six placentas with TAM included two stillborn cases. Microscopically, MCT was noted in all the cases, and a high incidence of FVM (50%) was observed in TAM cases. Immunohistochemically, MCT was found to be a platelet-rich thrombus. The placentas were grouped according to the presence or absence of TAM and subsequently compared. Clinically, the incidences of abnormal fetal heart rate pattern and fetal or neonatal death were significantly higher in TAM cases. Pathologically, placenta in TAM cases weighted more than those in cases without TAM, and the incidence of MCT was significantly higher in placentas with TAM. Moreover, the incidence of FVM was higher in placentas with TAM, but this difference was not statistically significant. We propose that MCT is a diagnostic feature of placentas with TAM and may be associated with poor fetal outcomes.
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特集 いま改めて妊娠高血圧症候群を考える-診療指針改訂のポイントから- 9.妊産婦死亡や重篤な後遺障害
桂木 真司
産婦人科の実際 71 ( 5 ) 499 - 507 2022年5月
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特集 Late preterm･Early termを展望する 各論 産科編-産科合併症･合併症妊娠の最適な分娩時期 心疾患合併妊娠
桂木 真司
周産期医学 52 ( 4 ) 508 - 515 2022年4月
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特集 循環器疾患合併妊娠患者の変化を見逃さない,妊娠から産後管理まで 治す15 循環器疾患をもつ女性の避妊と生殖医療の注意点
桂木 真司
Heart View 26 ( 3 ) 295 - 299 2022年3月
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急速に臨床所見が進行し予後不良であったp53陽性子宮体部類内膜癌の１例 査読あり
桂木真司
宮崎県医師会医学会誌 46 ( 1 ) 32 - 37 2022年3月
担当区分：責任著者 記述言語：日本語 掲載種別：研究論文（学術雑誌）
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出血性ショックをきたし母体救命できた卵管間質部妊娠の一例 査読あり
桂木真司
宮崎県医師会医学会誌 46 ( 1 ) 22 - 25 2022年3月
担当区分：責任著者 記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Myeloid cell thrombus and fetal vascular malperfusion in placentas with transient abnormal myelopoiesis 査読あり
Shinji Katsuragi
Virchows Archiv 480 1181 - 1187 2022年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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漿液性癌と未分化癌の子宮体部混合癌の１例 査読あり
桂木真司
日本婦人科病理学会誌 12 ( 1 ) 15 - 18 2022年2月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Hasegawa J., Tanaka H., Katsuragi S., Nii M., Sekizawa A., Ishiwata I., Ikeda T.
Journal of Maternal-Fetal and Neonatal Medicine 35 ( 26 ) 10451 - 10454 2022年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Purpose: Serious group A streptococcal (GAS) infections and toxic shock syndrome (TSS) are rare conditions, but their rapid progression often results in death. The purpose of the present study was to clarify recent trend after the coronavirus disease (COVID-19) pandemic of GAS infection in Japan. Materials and Methods: Maternal death statistics were analyzed by the Japan Maternal Death Exploratory Committee. Results: Maternal deaths due to GAS–TSS accounted for 4.2% (n = 22) of all maternal deaths in Japan (n = 525) in the last 12 years. GAS–TSS remains one of the leading causes of maternal death after obstetric hemorrhage and hypertensive disorder. However, no maternal deaths due to GAS–TSS have been reported since the COVID-19 pandemic in Japan after the last death occurred in February 2020. Conclusions: The major change during this period was that most Japanese people wore facemasks at all times and did frequent disinfection. It is considered that the reduction in the incidence of GAS infections itself reduced the number of serious GAS-related maternal deaths. Wearing facemasks and frequent disinfection during pregnancy might to be recommended to prevent various infectious diseases including serious GAS infection, even after the COVID-19 pandemic era.
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Tanaka H., Koide K., Nakamura M., Maki S., Takakura S., Enomoto N., Tanaka K., Katsuragi S., Sekizawa A., Ikeda T.
Journal of Maternal-Fetal and Neonatal Medicine 35 ( 25 ) 9131 - 9135 2022年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Purpose: The aim of this study was to measure the blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) before and after tadalafil treatment in patients with fetal growth restriction. Materials and methods: Maternal blood was collected from 13 women before and 2 weeks after tadalafil administration in the TADAFER II trial. The tadalafil treatment was conducted in addition to the conventional FGR treatment. As a control, maternal blood was also collected from 11 women before and 2 weeks after conventional treatment for fetal growth restriction. Blood sFlt-1 and PlGF were measured and the sFlt-1/PlGF ratio was calculated. Student’s t-test was used to statistically analyze differences in the sFlt-1 and PlGF levels, and in the sFlt-1/PlGF ratios. Results: In both treatment groups, the levels of sFlt-1 and PlGF before and after treatment were not significantly different from each other. The sFlt-1/PlGF ratio was 2.0 ± 1.0 before and 17.6 ± 11.3 after treatment in the control group (p=.04). The sFlt-1/PlGF ratio was 2.2 ± 1.1 before and 22.2 ± 10.6 after tadalafil treatment in the tadalafil group (p=.06). The sFlt-1/PlGF ratios before and after tadalafil treatment were significantly increased in the control group. In both treatment groups, the sFlt-1/PlGF ratios before and after treatment were less than 38. Conclusions: We conclude that the levels of sFlt-1 and PlGF were not significantly different as a result of tadalafil treatment. Further studies are needed to understand the mechanism of action of tadalafil in the treatment of fetal growth restriction.
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Detection of Treponema pallidum by immunocytochemistry of cervical smear: A case report
Noguchi H., Tokumitsu T., Kuroki E., Minematsu E., Asada Y., Kuroda S., Ochiai S., Kikuchi M., Fujimoto S., Onishi J., Kawagoe Y., Sameshima H., Katsuragi S., Sato Y.
Diagnostic Cytopathology 49 ( 12 ) E443 - E446 2021年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Diagnostic Cytopathology
Syphilis is an infectious disease caused by Treponema pallidum (T. pallidum). A cervical smear is useful when screening for sexually transmitted diseases; however, T. pallidum is not detected in the usual Papanicolaou smear. We report the detection of T. pallidum by immunocytological examination of a cervical smear. A 22-year-old woman presented with nephrotic syndrome. On admission, we performed screening tests for infections, and her serology was positive for syphilis. A Papanicolaou cervical smear (Thin-Prep) showed slight nuclear enlargement, nuclear irregularity, and mild hyperchromasia in the superficial cells, but no organism was detected. T. pallidum was detected in the remaining specimen using immunocytochemistry. We also detected the T. pallidum DNA in a cervical biopsy specimen by polymerase chain reaction (PCR). Our findings suggest that immunocytological examination and PCR assay examination are useful tests for syphilis diagnosis.
DOI： 10.1002/dc.24849
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Kawamura T., Tanaka H., Tachibana R., Yoshikawa K., Maki S., Toriyabe K., Takeuchi H., Katsuragi S., Tanaka K., Ikeda T.
Scientific Reports 11 ( 1 ) 2021年12月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
We aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.
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Maternal death related to sudden unexpected death in epilepsy: A nationwide survey in japan
Tanaka H., Katsuragi S., Hasegawa J., Tanaka K., Nakamura M., Hayata E., Nakata M., Sekizawa A., Ishiwata I., Ikeda T.
Brain Sciences 11 ( 8 ) 2021年8月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Brain Sciences
Sudden unexpected death in epilepsy (SUDEP) is defined as the sudden death of a patient with epilepsy in the absence of an anatomic or toxicologic cause. Whether pregnancy is a risk factor for SUDEP is unclear. Using data submitted to the Japan Association of Obstetricians and Gynecologists (JAOG), which has been collating information regarding all maternal deaths in Japan since 2000, this study evaluated maternal mortality data from 2010 to 2019 to evaluate the current circumstances of maternal death related to SUDEP in Japan. Six women died due to SUDEP during this period; the maternal mortality rate related to SUDEP was 0.066/100,000 individuals. Two women each died during the second trimester, third trimester, and postpartum period. Four and two women were receiving monotherapy and no therapy with anti-epileptic drugs, respectively. The duration of epilepsy was ≤15 years in three women, >15 years in one woman, and unknown in two women. This study furthers our understanding of the prevalence of maternal deaths due to SUDEP in Japan. Further studies are needed to confirm whether pregnancy is a risk factor for SUDEP.
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Pregnancy-associated hemorrhagic stroke: A nationwide survey in Japan
Enomoto N., Tanaka H., Katsuragi S., Hayata E., Hasegawa J., Nakata M., Takahashi J.C., Sekizawa A., Ishiwata I., Ikeda T.
Journal of Obstetrics and Gynaecology Research 47 ( 6 ) 2066 - 2075 2021年6月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Obstetrics and Gynaecology Research
Aim: The number of maternal deaths due to pregnancy-associated hemorrhagic stroke has not decreased despite a gradual decrease of maternal death in Japan. This study aimed to clarify the risk factors of hypertensive disorders of pregnancy-associated hemorrhagic stroke. Methods: This retrospective study analyzed pregnancy-associated hemorrhagic stroke patients with hypertensive disorders of pregnancy between 2013 and 2017 among 407 Japanese maternal and perinatal centers. Patients were divided into good or poor outcome groups and their maternal backgrounds and neonatal prognoses were compared. Results: We analyzed 61 cases, including 41 survival and 20 death cases, obtained from a secondary survey. Among the 61 hemorrhagic stroke cases, 62% were related to hypertensive disorders. Hypertensive disorders of pregnancy were observed in 75% of death cases. Use of MgSO4 or antihypertensive medication did not differ between the poor and good outcomes groups. In cases with antepartum onset of hypertensive disorders of pregnancy, outcomes were poor in 12 and good in 6 cases. Nine patients with poor outcomes and one with a good outcome had hypertension at the outpatient department without systemic evaluation (p = 0.043). Six poor outcomes patients and one good outcome spent more than 1 day from diagnosis at an outpatient clinic. Neurosurgery was performed in 11 poor outcome patients. Conclusion: Pregnant women who present with a hypertensive disorder at an outpatient clinic probably need to undergo blood tests and careful observation. Delayed systemic evaluation and intensive care for only a few days may result in the development of hemorrhage.
DOI： 10.1111/jog.14786
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Aortic dissection during pregnancy and puerperium: A Japanese nationwide survey
Tanaka H., Kamiya C.A., Horiuchi C., Morisaki H., Tanaka K., Katsuragi S., Hayata E., Hasegawa J., Nakata M., Sekizawa A., Ishiwata I., Ikeda T.
Journal of Obstetrics and Gynaecology Research 47 ( 4 ) 1265 - 1271 2021年4月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Obstetrics and Gynaecology Research
Aim: This study aimed to characterize the incidence and clinical significance of pregnancy-related aortic dissection using a large-scale survey in Japan. Methods: A questionnaire requesting the detailed information included in the clinical charts of pregnancy-related aortic dissection cases (without any personally identifying information) was designed between 2013 and 2017 and administered to 407 perinatal centers in Japan. The response rate was 70.5%. Seventeen cases of pregnancy-related aortic dissection were identified. Results: Maternal death due to aortic dissection was observed in nine patients (56.2%) while seven survived (43.8%). Dissection occurred during the postpartum period in 10 cases (62.5%), the third trimester in 4 (25.0%), labor in 1 (6.2%), and the second trimester in 1 (6.2%). The most common underlying diseases were: Marfan syndrome (25.0%), Loeys-Dietz syndrome (6.2%), hypertension (6.2%), and Takayasu aortitis (6.2%). Stanford type A aortic dissection was associated with maternal death during both pregnancy and the postpartum period. However, deceased patients showed lower rates of pre-diagnosed connective tissue disease than did survivors. Conclusions: The mortality rate of aortic dissection that occurred during pregnancy or postnatal periods was more than 50%. Aortic dissection occurred more frequently in the postnatal period than during pregnancy, and less frequently in women previously diagnosed with connective tissue disease than in women without any medical history of aortic disorders. If symptoms suggestive of aortic dissection, such as severe back pain, are observed, even after the end of pregnancy, exhaustive diagnostic examinations should be carried out.
DOI： 10.1111/jog.14657
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Pulmonary thromboembolism during pregnancy and puerperium: Comparison of survival and death cases
Takakura S., Tanaka H., Tanaka K., Katsuragi S., Hayata E., Nakata M., Hasegawa J., Sekizawa A., Ishiwata I., Ikeda T.
Journal of Obstetrics and Gynaecology Research 47 ( 4 ) 1312 - 1321 2021年4月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Obstetrics and Gynaecology Research
Aim: In Japan, the frequency of maternal deaths due to obstetric hemorrhage has been decreasing in the last decade, while that resulting from other causes such as pulmonary thromboembolism (PTE) was consistent. To help reduce maternal deaths due to PTE, we investigated PTE during pregnancy and puerperium and compared the survival and death cases, and aimed to find out life and death factors. Methods: This study was a retrospective analysis based on a clinical chart review in 407 maternal and perinatal centers. We compared the survival and death cases of PTE during pregnancy and puerperium from 2013 to 2017. Results: In PTE during pregnancy, the survival cases underwent significantly earlier diagnoses than the death cases, and thromboprophylaxis was performed in most of both the survival and death cases of PTE during puerperium according to the existing Japanese guidelines; however, only one fourth of the total cases underwent anticoagulation to prevent venous thromboembolism (VTE). Conclusions: Early diagnosis of PTE in suspected cases was associated with better survival during pregnancy.
DOI： 10.1111/jog.14687
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Reference range for C1-esterase inhibitor (C1 INH) in the third trimester of pregnancy
Tanaka H., Tanaka K., Enomoto N., Takakura S., Magawa S., Maki S., Nii M., Toriyabe K., Katsuragi S., Ikeda T.
Journal of Perinatal Medicine 49 ( 2 ) 166 - 169 2021年2月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Perinatal Medicine
The objectives of this study were to (i) establish the reference range and mean value for normal levels of C1-esterase inhibitor (C1 INH) during pregnancy, and (ii) investigate the association between C1 INH and uterine atony, as measured by blood loss at delivery. We prospectively studied 200 healthy pregnant women who were registered. We studied C1 INH levels in 188 women at 34 and 35 gestational weeks of pregnancy. The reference range for C1 INH during the third trimester of pregnancy was calculated using the value of C1 INH that was determined at registration. The mean value of C1 INH was determined to be 70.3% (95% confidence interval, 68.7-71.9). While the C1 INH levels in four women were determined to be 40% lower than the calculated mean value, amniotic fluid embolism (AFE) did not occur in any of the women studied. This study successfully demonstrated that a reference value for C1 INH activity can be established using the methods described herein. Further research is needed to determine whether C1 INH is involved in obstetric coagulopathy syndrome such as amniotic fluid embolism.
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Katsuragi S., Tanaka H., Hasegawa J., Kanayama N., Nakata M., Murakoshi T., Osato K., Nakamura M., Tanaka K., Sekizawa A., Ishiwata I., Yamamoto Y., Wakasa T., Takeuchi M., Yoshimatsu J., Ikeda T.
Journal of Maternal-Fetal and Neonatal Medicine 34 ( 3 ) 432 - 438 2021年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Objective: We reviewed malignancy related maternal deaths in Japan to ascertain if there were avoidable factors. Methods: Malignancy-related maternal death in Japan reported to the Maternal Death Exploratory Committee, from 2010 to 2016 inclusive. Results: There were 12 cases of maternal death caused by malignancy. There were four gastric cancers (two poorly differentiated adenocarcinoma, one signet ring cell carcinoma with adenocarcinoma, one histology not available), 3 leukemia (two acute myeloid leukemia, one aggressive NK cell leukemia), two ureteral cancers (histology not available), one malignant lymphoma (diffuse large B-cell lymphoma with translocation), one brain tumor (gliomatosis cerebri), and one cervical cancer (glassy cell carcinoma). Two gastric cancer patients had chronic gastric pain before conception. In two cases the physicians commented that they had avoided computed tomography and the brain biopsy needed for diagnosis because the patient was pregnant. At diagnosis, the clinical stages were II–IV in 9, and the performance status was 3–5 in 8. Indication for delivery was exacerbated maternal condition in 5, for treatment in 3, spontaneous labor in 3, and one patient declined elective delivery. Median [interquartile rage] (range) gestational weeks of delivery was 29 [24–30] (19–40). One cervical cancer patient had a radical hysterectomy and chemotherapy for 10 months. However, three leukemia and one gastric cancer patients had chemotherapy within 10 d because they deteriorated rapidly. Another seven cases did not have any treatment because of poor general condition or because they remained undiagnosed. In all cases, the Committee considered that there was no evidence of substandard care. Conclusion: In these cases, both the clinical stages and biological degree of malignancy were high. In two-thirds of cases, early termination of the pregnancy was indicated because of deteriorating maternal condition. Chemotherapy was not effective because of short available time for therapy and the advanced stage of the cancers when diagnosed. Encouraging women to have a thorough medical assessment before conception, and early diagnosis and treatment before pregnancy, appears to be the only practical way to reduce deaths from malignancy while a woman is pregnant.
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Stroke during pregnancy and puerperium among Japanese women: a single-center registry
Katsuragi S., Suzuki R., Toyoda K., Neki R., Miyamoto S., Iihara K., Takahashi J., Ikeda T., Yoshimatsu J.
Journal of Maternal-Fetal and Neonatal Medicine 34 ( 18 ) 2957 - 2964 2021年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Background: Stroke is one of the major causes of maternal death. This study aimed to analyze the maternal and fetal outcomes of stroke occurred during pregnancy and puerperium. Methods: We conducted a retrospective analysis of patients admitted to our perinatology center between 1982 and 2012 with a diagnosis of acute cerebral stroke during pregnancy or within 6 weeks postpartum. Results: Thirty-four patients were registered and all the patients had never been diagnosed as stroke nor detected cerebrovascular abnormalities before the current pregnancies. They were divided into 8 ischemic strokes (ISs) and 26 intracranial hemorrhage group. In the hemorrhage group, there was a spontaneous abortion and two patients chose artificial abortions to avoid rehemorrhage, and there were another three intrauterine fetal deaths (IUFDs) in the acute stage of maternal stroke. More patients in hemorrhage group delivered in preterm than in IS group for the treatment of stroke, 10/23 (43%) versus 0/8 (0%), p <.05. More patients in hemorrhage group had low Glasgow Coma Scale (GCS) (3–8) than in IS group at the onset of the stroke, 12/26 (46%) versus 0/8 (0%), p <.05. There were three maternal deaths and 6/23 (26%) were neurologically dependent in hemorrhage group in the chronic stage, whereas 87% were independent in IS group, p <.05. Conclusions: Hemorrhagic stroke was more common etiology of stroke related to pregnancy than IS in this study. Intensive and multidisciplinary care was needed especially in hemorrhagic stroke related to pregnancy as in the hemorrhagic stroke the fetal survival rate was lower, and maternal conscious levels at the onset of the stroke and neurological outcomes in the chronic stage were worse than IS.
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Retrospective study of pregnancies in women with Thr331Ala fibrinogen polymorphisms
Okumura A., Tanaka H., Tanaka K., Katsuragi S., Kamimoto Y., Ikeda T.
Journal of Maternal-Fetal and Neonatal Medicine 33 ( 23 ) 3894 - 3899 2020年12月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Background: We aimed to retrospectively review data of pregnant women with the α-fibrinogen Thr331Ala polymorphism; evaluate the relationship between this polymorphism and spontaneous abortion (SA), fetal growth restriction (FGR), and intrauterine fetal death (IUFD); and assess the effects of aspirin and/or heparin. Materials and methods: We examined the outcomes of 29 pregnancies (nine women) in women with the α-fibrinogen Thr331Ala polymorphism. Of these, 16 were untreated, whereas 13 were treated with heparin and/or aspirin. Results: The live birth rate was significantly higher in the treated group than in the nontreated group (69.2 versus 6.2%; p =.0004). In addition, the prophylactic use of a low dose of aspirin and/or heparin during early pregnancy in women with Thr331Ala may be an effective method for reducing fetal loss in these patients. Conclusions: This polymorphism interacts with pregnancy to result in poor obstetrical outcomes, but these effects can be mitigated with medical intervention. This study is the first to report outcomes of pregnancies complicated by the Thr331Ala polymorphism, which we believe may cause thrombophilia, SA, and IUFD. This study highlights the need for further research on this polymorphism in pregnancy.
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Tsuchiya K., Tanaka K., Tanaka H., Maki S., Enomoto N., Takakura S., Nii M., Toriyabe K., Katsuragi S., Ikeda T.
Medicina (Lithuania) 56 ( 12 ) 1 - 8 2020年12月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Medicina (Lithuania)
Background and Objectives: Fetal growth restriction (FGR) is associated with fetal mortality and is a risk factor for cerebral palsy and future lifestyle-related diseases. Despite extensive research, no effective treatment strategy is available for FGR. Mammalian target of rapamycin (mTOR) signaling is important for the growth of fetal organs and its dysregulation is associated with miscarriage. Here, we focused on mTOR signaling and investigated how the activities of phospho-ribosomal protein S6 (rps6) and phospho-eukaryotic translation initiation factor 4E (eIF-4E), which act downstream of mTOR signaling in the human placenta, change following treatment of FGR with tadalafil and aimed to elucidate the underlying mechanism of action. Placental hypoxia was investigated by immunostaining for hypoxia-inducible factor (HIF)-2α. Materials and Methods: Phosphor-rps6 and phosphor-eIF4E expression were examined by Western blotting and enzyme-linked immunosorbent assay, respectively. Results: HIF-2α expression significantly increased in FGR placenta compared with that in the control placenta but decreased to control levels after tadalafil treatment. Levels of phospho-rps6 and phospho-eIF-4E were significantly higher in FGR placenta than in control placenta but decreased to control levels after tadalafil treatment. Conclusions: Tadalafil restored the levels of HIF-2α, phospho-rps6, and eIF-4E in FGR placenta to those observed in control placenta, suggesting that it could be a promising treatment strategy for FGR.
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Katsuragi S., Okamura T., Kokubo Y., Watanabe M., Higashiyama A., Ikeda T., Miyamoto Y.
Journal of Obstetrics and Gynaecology Research 46 ( 3 ) 517 - 526 2020年3月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Obstetrics and Gynaecology Research
Aim: We previously reported that female babies born small developed cardiovascular risks in middle age. The present study was conducted using the same cohort to examine the relationship between physique at 6 years and the metabolic disease risk in middle age. Methods: Data collected from 721 women aged 41–69 years who underwent a medical examination at a single institution between 2007 and 2008 were retrospectively examined. We collected data from medical examinations and a questionnaire on physique (thin, normal, and fat) at 6 years. The relationship between birthweight and physique at 6 years was investigated. Results: Among females who were born small (< 2500 g), 80%, 16%, and 4% became thin, normal, or fat, respectively, by 6 years. Physique at 6 years had a negative relationship with future triglyceride, fasting glucose, HbA1C, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) levels and a positive relationship with high-density lipoprotein cholesterol levels. Conclusion: Although our findings may be specific to the study population, physique at 6 years had a negative relationship with the metabolic disease risk in middle-aged Japanese women. Insulin and MOMA-IR levels negatively correlated with physique at 6 years, and development from low birthweight infants to childhood obesity was rare in this cohort.
DOI： 10.1111/jog.14206
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Kikuchi H., Noda S., Katsuragi S., Ikeda T., Horio H.
PLoS ONE 15 ( 2 ) 2020年2月
掲載種別：研究論文（学術雑誌） 出版者・発行元：PLoS ONE
Objective: The relevance between time-series fetal heart rate (FHR) pattern changes during labor and outcomes such as arterial blood gas data at delivery has not been studied. Using 3-tier and 5-tier classification systems, we studied the relationship between time-series FHR pattern changes before delivery and umbilical artery blood gas data at delivery. Methods: The subjects were 1,909 low-risk women with vaginal delivery (age: 29.1 ± 4.4 years, parity: 1.7 ± 0.8). FHR patterns were classified by a skilled obstetrician based on each 10 min-segment of the last 60 min before delivery from continuous CTG records in an obstetric clinic. Results: The relationship between each 10 min-segment FHR pattern classification from 60 minutes before delivery and umbilical artery blood pH and base excess (BE) values at delivery changed with time. In the 3-tier classification, mean pH of Category I group in each 10 min-segment was significantly higher than that of Category II group. For Category I groups in each 10-minute segment, its number decreased and its average pH increased as the delivery time approached. In the 5-tier classification, there was the same tendency. About each level group in 10 min-segment, the higher the level, the lower the blood gas values, and mean pH of higher level groups decreased as the delivery time approached. Conclusions: The relationship between classifications and outcomes was clear at any time from 60 min before delivery in 3- and 5-tier classifications, and the 5-tier classification was more relevant.
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Katsuragi S., Tanaka H., Hasegawa J., Kurasaki A., Nakamura M., Kanayama N., Nakata M., Hayata E., Murakoshi T., Yoshimatsu J., Osato K., Tanaka K., Oda T., Sekizawa A., Shimaoka T., Ishiwata I., Takahashi J., Ikeda T.
Journal of Maternal-Fetal and Neonatal Medicine 1 - 6 2020年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Objective: The goal of this study is to find clues to improve perinatal outcomes in the case of cerebrovascular acute disorders during pregnancy. Study design: We analyzed 35 cases of cerebrovascular diseases related to maternal deaths in Japan those that occurred during pregnancy and reported to the Committee of the Ministry of Health, Labor, and Welfare from 2010 to 2018. Results: Cerebrovascular acute disorders occurred at 34.6 ± 6.6 gestational weeks. There were seven intrauterine fetal deaths (IUFD), and eight cases showed neonatal asphyxia with umbilical arterial pH between 6.7 and 7.0 (asphyxia cases, n = 15). In two of eight newborns, brain hypothermia therapy was given, and all survived without neurological sequelae. Maternal dyspnea was significantly related to severe prolonged decelerations of the fetus (p <.05), and asphyxia cases (p <.005). Median time from maternal onset to delivery (OD time) was significantly longer in asphyxia cases than in the non-asphyxia cases (84 vs 29 min, p <.05). OD time over 30 min was significantly related to the antepartum occurrence, cervical dilatation <5 cm (p <.05), onset outside of the hospital (p <.001), and maternal transfer before delivery (p <.001). Conclusion: More than 40% of cases experienced fetal asphyxia, and 20% ended in IUFD in maternal deaths related to cerebrovascular acute disorders. Maternal respiratory support and rapid delivery would be the keys to improve perinatal outcomes in case of cerebrovascular acute disorders during pregnancy.
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Katsuragi S., Okamura T., Kokubo Y., Watanabe M., Higashiyama A., Ikeda T., Miyamoto Y.
Journal of Atherosclerosis and Thrombosis 27 ( 3 ) 204 - 214 2020年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Atherosclerosis and Thrombosis
Aim: To investigate the relationship between perinatal condition around birth and cardiovascular risk in later life. Methods: Retrospective data were examined from 1241 city dwellers (521 men, 720 women; age 41–69 years) who had undergone medical examination at a single institution including blood tests and physical measurements from 2007 to 2008. The questionnaire was conducted to determine how perinatal factors affect their lives later. We also selected and studied a total of 28 individuals (12 men and 16 women) specifically about the conformity rate of the breastfeeding method between participants’ memories and what was written in the maternal and child health handbooks. Results: The conformity rate of the breastfeeding method between a self-questionnaire and his/her maternal and child health handbook was well correlated (r =0.73; p＜0.025). Among the data in women who were born at home, HbA1C levels (5.36±0.03 vs. 5.25±0.05 mg/dL, p=0.03) and low-density lipoprotein cholesterol (136.0±1.4 vs. 129.3±2.5 mg/dL, p=0.04) were higher than women who were born at the hospital. Women raised by formula showed higher low-density lipoprotein cholesterol levels than women fed breast milk or a mixture of breast milk and formula (150.2±4.8 vs. 138.7±3.7, 142.5±2.6 mg/dL, p =0.04). Fasting blood glucose levels at an adult time in men and women born through breech presentation were higher than those by the cephalic presentation (123.2±7.8 vs. 106.8±1.2 mg/dL, p=0.03). Conclusion: The study proposed that some perinatal conditions around birth such as delivery place, presenting part, and lactation affected especially Japanese women’s cardiovascular risks between ages 41 and 69 years.
DOI： 10.5551/jat.49577
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Risk factors for cardiovascular events among pregnant women with cardiovascular disease
Nii M., Tanaka H., Tanaka K., Katsuragi S., Kamiya C.A., Shiina Y., Niwa K., Ikeda T.
Internal Medicine 59 ( 9 ) 1119 - 1124 2020年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
Objective: Cardiovascular disease increases the risk of maternal mortality. This study examined the risk factors for cardiovascular events in pregnant women with cardiovascular disease. Methods: This was a case-control study conducted in 2 phases at Japanese maternal and fetal care centers. The primary survey, using an interviewer-administered questionnaire, investigated whether the institutions had managed pregnant women with cardiovascular disease from April 2014 to March 2016. From 424 individual facilities surveyed, 135 facilities were found to have experience in managing pregnant women. In the secondary survey, the 135 institutions were asked to complete a web-based questionnaire, which collected detailed clinical information about cases, including cardiovascular disease, cardiovascular events, maternal background, and the perinatal outcome. Results: Information on 302 pregnant women with cardiovascular disease was collected. None of the 302 patients died. There were 25 women with cardiovascular events (cardiovascular event group) and 277 women without cardiovascular events (non-cardiovascular event group); the two groups were compared. No significant differences were found in the perinatal outcomes. Medication use before pregnancy was identified as a risk factor for cardiovascular events (adjusted odds ratio, 23.28; 95% confidence interval, 8.15-66.47; p< 0.001). In pregnant women with cardiovascular disease, New York Heart Association (NYHA) functional class II or III before pregnancy was associated with a higher risk of cardiovascular events in comparison to NYHA functional class I (p<0.001 for both). Conclusion: Medication use before pregnancy and NYHA functional class >I were risk factors for cardiovascular events in pregnant women with cardiovascular disease.
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Katsuragi S., Parer J.T., Noda S., Onishi J., Kikuchi H., Ikeda T.
Journal of Maternal-Fetal and Neonatal Medicine 28 ( 13 ) 1608 - 1613 2015年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
© 2014 Informa UK Ltd. All rights reserved. Objective: We have reported a 7-fold reduction in newborn umbilical arterial (UA) metabolic acidemia after adoption of a rule-based 5-category color-coded fetal heart rate (FHR) management framework. We sought evidence for the relationship being causal by detailed analysis of FHR characteristics and acid-base status before and after training. Methods: Rates of UA pH and base excess (BE) were determined over a 5-year period in a single Japanese hospital, serving mainly low-risk patients, with 3907 deliveries. We compared results in the 2 years before and after a 6-month training period in the FHR management system. We used a previously published classification schema, which was linked to management guidelines. Results: After the training period, there was an increase in the percentage of normal patterns (23%), and a decrease in variable decelerations (14%), late decelerations (8%) and prolonged decelerations (12%) in the last 60 min of labor compared to the pre-training period. There was also a significant reduction in mean UA pH and BE in the groups with decelerations after introduction of the FHR management framework. Conclusions: The adoption of this FHR management system was associated with a reduction of decelerations and metabolic acidemia, without a change in cesarean or vacuum delivery rates. These results suggest that the obstetrical providers were able to better select for intervention those patients destined to develop more severe acidemia, demonstrating a possible causal relationship between the management system and reduced decelerations and metabolic acidemia.
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Katsuragi S., Ikeda T., Noda S., Onishi J., Ikenoue T., Parer J.T.
Journal of Maternal-Fetal and Neonatal Medicine 26 ( 1 ) 71 - 74 2013年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Objective: To determine whether a rule-based system for fetal heart rate interpretation can result in reduced metabolic acidemia without increasing obstetrical intervention. Methods: Rates of vacuum-assisted delivery and Cesarean sections, and umbilical artery pH and base excess values were determined over a 5-year period in a single hospital with 3907 deliveries in Japan. Results were compared for 2 years before and 2 years after a 6-month training period in rule-based fetal heart rate interpretation. Results: The pre- and post-training rates of unscheduled Cesarean deliveries (4.8% vs. 6.0%) and vacuum deliveries (21.2% vs. 18.1%) did not differ significantly. The rates of umbilical arterial pH <7.15 (1.51% vs. 0.18%, p < 0.05) and base excess <-12 mEq/L (1.76% vs. 0.25%, p < 0.05) were significantly lower after training. Conclusion: A standardized fetal heart rate pattern management system was associated with a 7-fold reduction of newborn metabolic acidemia with no change in operative intervention. © 2013 Informa UK, Ltd.
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新生児低酸素性虚血性脳症に対するグリア細胞由来神経栄養因子による治療戦略
桂木 真司, 池田 智明, 池ノ上 克
脳と発達 43 ( 4 ) 265 - 272 2011年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本小児神経学会
 新生仔ラットの脳内におけるグリア細胞由来神経栄養因子 (GDNF) の発現量は発達とともに変化する. 低酸素虚血負荷を与えたラットの脳内では結紮側の受傷部位において特にGDNFが増加する. 外因性のGDNFを脳に直接作用させるため, 細胞にGDNFの遺伝子を導入し, 半透膜製カプセル内に充填し, 大脳実質内に移植する方法を開発した. この方法は長期間, 低用量の薬剤を安全に供給できる特徴を持つ. 同方法を低酸素虚血負荷を与えた新生仔ラットに応用した. 梗塞面積は著明に減少し, 神経保護効果を持つことが示された. また, 同方法は低酸素虚血負荷後の記憶と学習障害に関しても長期にわたり優れた改善効果を示した.
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Katsuragi S., Ikeda T., Ikenoue T.
No To Hattatsu 43 ( 4 ) 265 - 272 2011年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：No To Hattatsu
Hypoxic-ischemic encephalopathy is one of the main causes of neurological disabilities. It has been reported that the infarcted area can be reduced by injection of glial cell line-derived neurotrophic factor (GDNF) into the brain parenchyma after a hypoxic/ischemic insult in neonatal rats. We have shown that GDNF is expressed in neuronal and non-neuronal cells throughout all regions of the developing rat brain. We developed a system for the delivery of a constant supply of glial cell line-derived neurotrophic factor to the brain via implantation of GDNF secreting cells directly into the brain parenchyma. The aim of this study was to examine the neuroprotective effect of GDNF using this delivery system. We implanted a capsule containing GDNF secreting cells in 7 day old Wistar rats, and two days later, they underwent hypoxic-ischemic stress. The capsule provided strong neurological protection, as indicated by a reduction in the infarcted area and the severity of histological damage in the treated group compared with controls. We then investigated whether this new delivery method improved the long time learning and memory disability caused by hypoxic-ischemic stress. We examined the effect of implantation of the cells on three tasks : 1) eight arm radial maze task for short memory ; 2) choice reaction time task for reference memory; and 3) water maze task for long term memory. In all of the three tasks, implantation of the GDNF capsule improved learning and memory disability. Glial cell line-derived neurotrophic factor treatment is effective not only in reducing brain damage but also in preventing learning and memory impairment following hypoxic-ischemic insult in neonatal rats.
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桂木 真司, 鮫島 浩, 池ノ上 克
日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology 16 ( 1 ) "S - 17"-"S-18" 2006年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Katsuragi S., Ikeda T., Date I., Shingo T., Yasuhara T., Ikenoue T.
American Journal of Obstetrics and Gynecology 192 ( 4 ) 1137 - 1145 2005年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Obstetrics and Gynecology
Objective: It has been reported that an infarcted area is reduced by the injection of glial cell line-derived neurotrophic factor into brain parenchyma after hypoxic/ischemic insult in neonatal rats. For use of glial cell line-derived neurotrophic factor in humans, we have developed a system for the delivery of a constant supply of glial cell line-derived neurotrophic factor to the brain. The aim of this study was to examine the neuroprotective effect of glial cell line-derived neurotrophic factor with the use of this delivery system. Study design: Baby hamster kidney cells were transfected with human glial cell line-derived neurotrophic factor complementary DNA, encapsulated in semipermeable hollow fibers, and implanted into the left cerebrum of 12-day-old Wistar rats (glial cell line-derived neurotrophic factor group, 11 rats). Nontransfected baby hamster kidney cells served as controls (control group, 9 rats). Two days after implantation, the rats received a hypoxic/ischemic stress, with a modification of Levine's method. Seven days later the rats were killed, and coronal brain slices were cut 2, 4, 6, 8, and 10 mm from the anterior pole. The cortex, hippocampus, striatum, and thalamus were evaluated for damage severity. The serum concentrations of glial cell line-derived neurotrophic factor were also determined. Results: The left brain hemispheric area was significantly larger; the neuronal damage to each brain region was significantly less, and the serum glial cell line-derived neurotrophic factor concentrations were significantly higher in the glial cell line-derived neurotrophic factor group, compared with the control group. Conclusion: Grafting of encapsulated glial cell line-derived neurotrophic factor-secreting cells is a promising way to protect the neonatal brain from hypoxic/ischemic insult. © 2005 Elsevier Inc. All rights reserved.
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Katsuragi S., Ikeda T., Date I., Shingo T., Yasuhara T., Mishima K., Aoo N., Harada K., Egashira N., Iwasaki K., Fujiwara M., Ikenoue T.
American Journal of Obstetrics and Gynecology 192 ( 4 ) 1028 - 1037 2005年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Obstetrics and Gynecology
Objective: Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells into brain parenchyma reduces histological brain damage following hypoxic-ischemic stress in neonatal rats. We examined the effect of glial cell line-derived neurotrophic factors on long-term learning and memory impairment and morphological changes up to 18 weeks after hypoxic-ischemic stress in neonatal rats. Study design: Baby hamster kidney cells were transfected with expression vector either including (glial cell line-derived neurotrophic factor-hypoxic-ischemic group; n = 10) or not including (control-hypoxic-ischemic group; n = 8) human glial cell line-derived neurotrophic factor cDNA, encapsulated in semipermeable hollow fibers, and implanted into the left brain parenchyma of 7-day-old Wistar rats. Two days after implantation the rats received hypoxic-ischemic stress, and their behavior was then examined in several learning tasks: the 8-arm radial maze, choice reaction time, and water maze tasks, which examine short-term working memory, attention process, and long-term reference memory, respectively. The rats were killed 18 weeks after the hypoxic-ischemic insult for evaluation of brain damage. Two additional control groups were used: the control group (n = 15), which underwent no treatment, and the glial cell line-derived neurotrophic factor group (n = 6), which underwent implantation of the glial cell line-derived neurotrophic factor capsule but did not undergo hypoxic-ischemic stress. Results: The decrease in the size of the cerebral hemisphere was significantly less in the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, compared with the control-hypoxic-ischemic group, and improved performance was observed in all three tasks for the glial cell line-derived neurotrophic factor-hypoxic-ischemic group: for the control-hypoxic-ischemic group versus the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, respectively, in the 8-arm radial maze test, average number of correct choices was 6.2 ± 0.1 versus 6.9 ± 0.1 (P < .01); in the choice reaction time test, average reaction time for a correct response was 2.35 ± 0.1 seconds versus 1.97 ± 0.09 seconds (P < .01); in the water maze test, average swimming length was 1120.0 ± 95.2 cm versus 841.6 ± 92.1 cm (P < .01). All results for the glial cell line-derived neurotrophic factor group were similar to those for the control group. Conclusion: Glial cell line-derived neurotrophic factor treatment is effective in not only reducing brain damage but also inhibiting learning and memory impairment, following hypoxic-ischemic insult in neonatal rats. No adverse effects in learning and memory tests were observed in the glial cell line-derived neurotrophic factor group. © 2005 Elsevier Inc. All rights reserved.
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Asphyxia 性脳障害の診断に関する臨床的および基礎的研究
池田 智明, 池ノ上 克, 鮫島 浩, 金子 政時, 川越 靖之, 古川 誠志, 米田 由香里, 大西 淳仁, ト部 浩俊, 大里 和広, 山下 理絵, 田中 博明, 福島 和子, 村田 雄二, QUILLIGAN Edward J., CHOI Ben H., PARK Soung-Day, 土井 茂治, PARER Julian T., 児玉 由紀, 寺尾 公成, 西口 俊裕, 河野 慶一郎, 嶋本 富博, 春山 康久, 今村 登志子, 桂木 真司, 高崎 泰, 三輪 勝洋, 徳永 修一, 山内 憲之, 園田 徹, 布井 博幸
日本新生児学会雑誌 39 ( 4 ) 724 - 732 2003年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）