Prenatal and Peripartum Management of Patients with Hypofibrinogenemia Resulted in Two Successful Deliveries

Fibrinogen is an essential agent involved in maintaining pregnancy and coagulation. Since inherited fibrinogen disorders introduce greater risks for conditions such as placental abruption and postpartum hemorrhage, careful prenatal and perinatal management is essential for this patient population. We report two cases of successful deliveries in patients with hypofibrinogenemia. Case 1 is of a 26-year-old (gravida 1, para 1) woman. The patient’s fibrinogen level increased spontaneously to higher than 300 mg/dL during pregnancy, without treatment. She delivered at week 38 of gestation, with no complications. Case 2 is of a 30-year-old (gravida 3, para 1) woman. We performed repeated infusions of fibrinogen to maintain the level higher than 100 mg/dL during pregnancy and at least 200 mg/dL in the perioperative period; the patient delivered a healthy infant. We identified a new mutation, Hiroshima I (γ278Tyr→His). It is important to maintain appropriate fibrinogen levels in cases of inherited fibrinogen disorders for successful prenatal and peripartum management

Resectable hepatoblastoma with tumor thrombus extending into the right atrium after chemotherapy: A case report

AbstractHepatoblastoma with intraatrial tumor thrombus is relatively rare. We report a case of hepatoblastoma with tumor thrombus extending into the right atrium, which responded well to chemotherapy and was resected using extracorporeal circulation. A 4-year-old girl was referred to our hospital because of abdominal distention and tenderness. A computed tomography (CT) scan showed a large tumor occupying the left 3 segments of the liver with tumor thrombus extending into the right atrium. There was also a small intrahepatic metastasis in the right lobe of the liver. She was diagnosed with hepatoblastoma on the basis of the results of open biopsy. Neoadjuvant chemotherapy with an intense CDDP-based regimen was performed. The tumor responded well to chemotherapy, and intrahepatic metastasis became undetectable on CT scan, although the tumor thrombus remained in the right atrium. After 7 courses of chemotherapy, we performed resection using extracorporeal circulation. The postoperative course was uneventful, and adjuvant chemotherapy was started 10 days after the operation. Her serum alpha-fetoprotein (AFP) level decreased to the normal range, and she was free of disease for 1 year after the operation. Tumor resection using extracorporeal circulation can be performed safely and is justified in patients with intraatrial tumor thrombus

Psychosocial support for the examinees and their families during the secondary confirmatory examination: Analyses of support records at first visit

Background and Purpose The Thyroid Ultrasound Examination (TUE) program is conducted as part of the Fukushima Health Management Survey. Following the established criteria, examinees are called in for a secondary confirmation examination, which may induce high anxiety related to a thyroid cancer for both the examinees and their families. Therefore, Fukushima Medical University created the Thyroid Support Team to reduce anxiety. The purpose of this study is to analyze the psychosocial support for examinees and their families through two types of records, and to clarify the current issues and determine future directions of support. Materials and methods We analyzed 223 records of support for the first visit of examinees who attended the secondary confirmatory examination, conducted at Fukushima Medical University from September 2018 to March 2019. Results During the first visit, frequent topics and questions brought up by the examinees and their families were about the "Thyroid Ultrasound Examination (TUE) program" and "Examination findings". The Thyroid Support Team members assisted them by "Responding to questions", "Confirming the doctor's explanation" and "Providing information". The percentage of people with high anxiety decreased in both examinees and their family members after the examination. The level of anxiety was lower among those who had already taken the secondary confirmatory examination. Family members' anxiety was significantly higher than that of the examinees, and anxiety levels were highly correlated between examinees and their families. Conclusion The psychosocial support for examinees and their families was important in reducing their anxiety. Currently there are changes in social conditions and various opinions concerning the TUE. Thus, careful explanation and the need for decision-making supports for the examinees and their families increased. Also, we should take into account the aging of the examinees and expanding the available psychosocial support

Effects of Physical Exercise and of Dietary Protein Levels on Nitrogen Retention in Energy-Restricted Adult Rats

たんぱく質および脂肪含量が異なる種々の実験食を自由摂取時の50〜60%量与え, 同時に1日30分のトレッドミル歩行(20m/分)または50分の遊泳を課して10〜35日間減量させた成熟ラット(約100日齢)について, 窒素出納, 体組成, 血液性状, 筋グリコーゲン量などを測定し, 以下の成績が得られた.1.食餌制限した運動負荷ラットは, たんぱく質摂取水準が等しい非運動ラットに比べて窒素保留量の増加がみられ, 体構成的にも水分とたんぱく質が多くなり脂肪が著るしく減少した.2.運動・非運動群ともに, 25%カゼイン食給与ラットは10%および40%カゼイン食ラットと比較すると, 窒素出納が正に傾き, 減食に伴う体たんぱく質の損失も著るしく軽減された.3.食餌制限下においても, 運動群ラットの血清コレステロール値は同一食の非運動群ラットよりも低下する傾向が認められた.また, 自由摂取時に血清コレステロール上昇作用をもつラードとカゼインは食餌中の添加量が増すにつれ, 減食中のラットに対しても血清コレステロール値を高めるように作用した.4.10%カゼイン食給与ラットを食餌制限と運動負荷を併用して減量させると貧血傾向が出現したが, 25%および40%カゼイン食ラットではこの傾向は認められなかった.運動群ラットの筋グリコーゲン量は非運動群ラットに比べて著明に増加した.以上の結果から, 減食時の運動は体たんぱく質さらには活性組織の損失を抑制し体脂肪の減少を促進するほかに, 血清コレステロール値を低下させ筋グリコーゲン量を高めるなど, 体力・保健上有利な作用を示すことが明らかになった.また, 減食時の体構成の変化に食餌たんぱく質量, 血清コレステロール値には食餌脂肪がそれぞれ強く影響する

TT ウイルス ボシ カンセン ノ コウホウシテキ, ゼンホウシテキ ケンキュウ : トクニ ボシ カンセン ヨウシキ ト シュウサンキ ニオケル リンショウテキ イギ ニツイテ

近年同定され,輸血後肝炎との関連が示唆されているTTV について,その母子感染の自然史と周産期における臨床的意義について後方視的,前方視的に検討した.HBV 及びHCV が検出されない妊婦(前方視的研究;NBCPW 群)におけるTTV DNA 陽性率は19.0%(37/195)であり,このうちsAST/sALT 値が110 U/L を超える例は皆無であった.HBV あるいはHCV キャリア妊婦(後方視的研究;BCCPW 群)ではTTV DNA 陽性率は25.0%(21/84)である.このうちsAST/sALT 値が110U/L を超える例は23.8%(5/21)に達し,この5 例はTTV 単独キャリアではなく,HBV 又はHCV との重複キャリアであった.NBCPW 群の出生児(14 名)におけるTTV DNA 陽転率は57.1%であり,このうちsAST/sALT 値が110 U/L を超えた例は無かった.BCCPW 群の出生児(21 名)におけるTTV DNA 陽転率は42.9%であり,このうちsAST/sALT 値が110 U/L を超えた児は2 名(22.2%)で,この2 名はHCV キャリアでもあった.TTV DNA 陽転化した総数17 名の出生児は全員生後18 ヶ月時点までTTV DNA 陽性が持続しており,脱キャリア化は認められていない.また,キャリア化児におけるTTV DNA 出現時期および哺育方法より経胎盤感染,経産道感染および経唾液感染は否定的であり,経母乳感染の可能性が強く示唆される結果であった.また,キャリア妊婦及びキャリア化児における肝機能異常は母子共々TTV 単独キャリアでは認められず,TTV 感染の周産期における臨床的インパクトは低いと思われる.The natural history of mother-to-child transmission(MTCT) of the TT virus (TTV) was investigated retroandprospectively.Serum TTV DNA was detected in 37 out of the 195( 19.0%) pregnant women without both HBV and HCV in theirsera (NBCPW) and 21 out of the 84 (25.0 %) pregnantwomen with HBV and/or HCV (BCCPW). In the lattergroup, 5 out of the 21( 23.8%) TTV carrier pregnant womenshowed repeatedly sAST and/or sALT levels over110U/L, but none of the former group did.With informed consent (IC), 14 (NBCPW) and 21 (BCCPW)infants were followed from birth up to 18 months ofage by receiving tests for serum TTV DNA and levels ofsAST and sALT. Eight out of the 14 infants (57.1 %, NBCPW)and 9 out of the 21 infants( 42.9%, BCCPW) developedTTV carrier-state, and all of these 17 carrier infantsmaintained serum TTV DNA-positive through the followupperiods. No infants (NBCPW) showed elevated serumlevels (>110 U/L) of AST or ALT during the follow-upperiods, but 2 out of the 9 infants( 22.2%, BCCPW) showedsAST or sALT levels higher than 110 U/L, and these 2 infantswere found to be in HCV carrier-state.None of the infants developed a TTV-positive resultwithin 1 month after birth, and thereafter 11.8 % (2/17)developed carrier-state in 3 months, 47.1 % in 6 months,82.4 % in 12 months. These findings may exclude the intrauterineor trans-vaginal infection as a mode of TTVMTCT. On the other hand, all carrier infants with one exceptionwere raised by breast feeding, which was rich inTTV. Both carrier pregnant women and children, who wereneither HBV nor HCV carriers, showed no abnormal liverfunction through the follow-up periods.Thus, we conclude that TTV MTCT occurs highly, but itis not so significant practically

シュウサンキ リョウイキ ニオケル Gガタ カンエン ウイルス ノ リンショウテキ イギ : オナジ フラビ ウイルス カ ニ ゾクスル Cガタ カンエン ウイルス ト ヒカク シテ

HBV, HCV 同様血清肝炎を惹起する可能性を示唆されているHGV の(1)妊婦における検出率,(2)母子感染の自然史,そのリスクファクター及びキャリア化児の予後,(3)キャリア妊婦及びキャリア化児における肝機能を前方視的に調査し,同ウイルスの周産期における臨床的意義を同じフラビウイルス科に属するHCV と比較検討した.対象は1996〜2004 年に当科を受診した妊婦3,738 名(HGV),4,023 名(HCV)とキャリア妊婦の出生児14 名(HGV),24 名(HCV)である.HGV RNA は RT-PCR 法(定性)k,real-time PCR(定量)及びcycle-sequence 法(genome sequence)により,HGV-E2 抗体はELISA 法を用いて,またHCV RNA はnested RT-PCR(定性),real- time PCR(定量)により,またHCV-Ab は2nd 及び3rd generation EIA を用いて測定した.対象児の血清サンプルは臍帯血から最長119 ヶ月まで定期的に検査に供された.妊婦におけるHGV RNA, HCV RNA の検出率は各々0.64%(24/3,738),0.60%(24/4,023)であり両者に有意差を認めなかった(p=0.7984).HGV-E2 抗体の検出率は4.4%(82/1,858)であり,HGV RNA とHGV-E2 抗体は相互排他的であった.HGV RNA 単独陽性妊婦で肝機能異常は見られなかった.出生児におけるHGV RNA,HCV RNA 陽性はそれぞれ64.3%(10/16),12.5%(3/24)に認められ,両ウイルス陽性児とも経膣分娩症例であり,キャリア妊婦のviral loads はそれぞれ107 及び105 copies/ml 以上の症例であった.HGV 母子感染と推測された4 組の母子ペア血清を用いたHGV RNA シークエンス相同性の検討では各母子間で100%の一致率が得られ,HGV 母子感染の直接的証拠が得られた.キャリア化した9 名の児のうち1名が肝機能異常(sALT 値>110 U/L)を呈したが,これはHCV との重複感染例であった.フォローアップ中にHCV では約16.7%がキャリア化後3 年以内に脱キャリア化したが,HGV キャリア児ではRNA 陰性化は少なくとも最長約10 年間のフォローアップ期間中には皆無であった.妊婦のHGV 及びHCV 保有率(キャリア率)はほぼ同等であり,一方母子感染率は前者が後者の約5.1 倍に達し,母子感染がHGV キャリアの主たる供給源であることが示唆された.HGV およびHCV 母子感染では,キャリア妊婦の血中viral loads 及び経膣分娩がリスクファクターであることが示された.さらに,同じフラビウイルス科に属しながら,HGV はHCV とは異なり,肝傷害性が殆ど無いことが判明した.The epidemiology and natural history of mother-to-childtransmission( MTCT) of hepatitis G virus( HGV) were investigatedto evaluate potential clinical significance of HGVin perinatal periods. The data was discussed by comparisonwith those of a well-known flavivirus, hepatitis C virus(HCV).During the periods from 1996 to 2006, 3,738 pregnantwomen received screening tests for HGV RNA and 4,023pregnant women received screening tests for HCV Antibodies(Ab). HGV RNA-positive pregnant women weretested for HGV-E2 Ab and HCV Ab-positive pregnantwomen were tested for HCV RNA. HGV- and HCV RNApositivewomen underwent the measurement of viral loadswith use of real-time PCR. With informed consent, 14 infantsborn to HGV carrier mothers and 24 infants born toHCV carrier mothers were followed from birth to 19months of age by receiving the measurement of serumHGV- or HCV RNA and sAST/sALT levels.HGV RNA was detected in 0.64 % (24/3,738) of thewomen tested and HCV RNA was detected in 0.60 %(24/4,023) of the women tested. HGV-E2 Ab was detectedin 4.4 % and mutually exclusive with HGV RNA. Nine ofthe 14 infants born to HGV carrier mothers( 64.3%) and 3of 24 infants born to HCV carrier mothers (12.5 %) developedHGV and HCV carrier-states respectively. The homologyof HGV RNA sequences was perfectly identical betweenthe 4 paired sera of mother-child.Both of vaginal delivery mode and maternal viral loads atdelivery (HGV>107, HCV>105 copies/ml) were suggestedas one of risk factors for MTCT. The elevation of sAST/sALT levels (>110 U/L) in the HGV and HCV carrier infantswere 7.1%( 1/9) and 66.7%(2/3) respectively. However,one HGV carrier infant with elevated sAST/sALTlevels was found to be a HCV carrier.We conclude that HGV MTCT occurs very frequently,but HGV is not so significant in perinatal periods comparedwith another flavivirus, HCV

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target