Utilizing Repetitive Serial Placental Ultrasounds for Diagnosing a Massive Subchorionic Thrombohematoma: Insights Into Soluble FMS-Like Tyrosine Kinase-1/Placental Growth Factor (sFlt-1/PlGF) Trends.

The patient, a 34-year-old primigravida with no prior medical history, presented at 23 + 0 weeks with gestational hypertension and fetal growth restriction (FGR). Ultrasound examination showed a placental mass, and subsequent repeated ultrasound scans revealed changes in the mass' echogenicity, raising suspicion of a massive subchorionic thrombohematoma (MST). While the blood pressure was mildly elevated without proteinuria and organ dysfunctions, serum soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratios showed significantly elevated values. A cesarean section was performed at 29 + 2 weeks due to the nonreassuring fetal status. The female infant, with Apgar scores of 1/1 at one/five minutes and an umbilical artery pH of 7.16, remained unresponsive and died seven hours postdelivery. Pathology examination revealed a massive hematoma in the subchorionic space, measuring 22 mm thick, directly beneath the umbilical cord attachment. This case underscores the importance of repetitive placental ultrasound in MST diagnosis and suggests the potential utility of sFlt-1/PlGF ratios in predicting adverse outcomes.

Missense BICD2 variants in fetuses with congenital arthrogryposis and pterygia.

Type 2 spinal muscular atrophy with lower extremity dominance (SMALED2) is caused by bicaudal D cargo adaptor 2 (BICD2) variants. However, the SMALED2 genotype and phenotype correlation have not been thoroughly characterized. We identified de novo heterozygous BICD2 missense variants in two fetuses with severe, prenatally diagnosed multiple arthrogryposis congenita. This report provides further insights into the genetics of this rare disease.

Clinical course and genetic analysis of a case of the amniocentesis showing chromosome 6 trisomy mosaicism.

OBJECTIVE: Herein, we present a case of mosaic trisomy 6 detected by amniocentesis. CASE REPORT: Amniocentesis (G-banding) was performed at 17 weeks of gestation; the results were 47,XY,+6[3]/46,XY[12]. Fetal screening ultrasonography showed no morphological abnormalities, and the parents desired to continue the pregnancy. The infant was delivered vaginally at 39 weeks' gestation. The male infant weighed 3002 g at birth with no morphological abnormalities. G-banding karyotype analysis performed on the infant's peripheral blood revealed 46,XY[20]. FISH analysis revealed trisomy signals on chromosome 6 in 1-4 out of 100 cells from the placenta. The single nucleotide polymorphism microarray of the umbilical cord blood revealed no abnormalities. Methylation analysis of umbilical cord blood revealed no abnormalities in PLAGL1. No disorders were observed at one year of age. CONCLUSION: When amniocentesis reveals chromosomal mosaicism, it is essential to provide a thorough fetal ultrasound examination and careful genetic counseling to support the couples' decision-making.

Recurrent severe anemia associated with a jejunal arteriovenous malformation in pregnancy: A case report.

Background: Small intestinal arteriovenous (AV) malformations may cause gastrointestinal hemorrhage, occasionally leading to anemia; however, they are rarely seen in pregnancy. This report presents a case of a pregnant woman who had recurrent severe anemia that was attributed to a small hemorrhagic intestinal arteriovenous malformation. Case Presentation: A 24-year-old pregnant woman (gravida 2, para 1) presented with a low hemoglobin concentration (3.6 g/dL) in her first pregnancy and underwent an emergency cesarean section at 36 weeks due to non-reassuring fetal status. In her second pregnancy, she was hospitalized at 30 weeks with epigastric pain and nausea. A low hemoglobin level (6.6 g/dL) and scant fecal occult blood were revealed upon examination. She was referred to the hospital for further evaluation and pregnancy management. Recurrent blood transfusions were required; however, neither hematemesis nor obvious fecal hemorrhage was observed. At 31 weeks, a cesarean section was performed owing to persistent anemia. Postoperative small intestinal capsule endoscopy and flexible fiberoptic proximal small intestinal endoscopy revealed a suspected bleeding small intestinal arteriovenous malformation. The patient underwent partial resection of the small intestine on hospitalization day 16. Histopathological examination confirmed a small intestinal arteriovenous malformation. The patient had a good postoperative course and was discharged on hospitalization day 24. Conclusions: Small intestinal arteriovenous malformations can bleed during pregnancy. They can go undetected if they spontaneously shrink postpartum. In severe anemia during pregnancy, hemorrhage from small intestinal arteriovenous malformations should be included in the differential diagnosis and promptly investigated even in the absence of gastrointestinal symptoms.

Managing a case of Breus' mole with severe fetal growth restriction via sequential ultrasonographic imaging and MRI.

A Breus' mole is a massive subchorionic thrombohematoma that arises below the chorionic plate on the fetal side of the placenta. It requires careful perinatal management because of the associated high incidence of severe fetal growth restriction and intrauterine fetal demise. However, the mechanism of its development remains unclear, and there are no reports examining the continuous changes in the hematomas. Herein, we report a case of a Breus' mole in which ultrasonographic massive subchorionic thrombohematoma changes were observed during pregnancy. A 40-year-old pregnant patient presented with fetal growth restriction, a hematoma with a highly echoic lesion, and an extremely thickened placenta. The clinical picture of massive subchorionic thrombohematoma gradually changed from a high-echoic phase with a 7-cm thick placenta to a high- and low-echoic mixed phase to a completely low-echoic phase with a prominent atrophic placenta (placental thickness = 3.5 cm) in almost 8 weeks. At 34 weeks of gestation, a male infant was delivered via cesarean section due to its nonreassuring fetal status with extremely low birth weight (1230 g). Postpartum histological findings revealed the presence of a Breus' mole. In conclusion, we observed the ultrasonographic changes of the massive subchorionic thrombohematoma that were detected as a placental hemorrhagic infarction by magnetic resonance imaging, from a high- to low-echoic area. The clinical course from massive subchorionic thrombohematoma to Breus' mole may be a prominent atrophic change in the placental tissue during pregnancy. These sequential ultrasonographic findings could be a key factor in understanding the pathophysiology of Breus' moles.

COVID-19 mRNA vaccination status and concerns among pregnant women in Japan: a multicenter questionnaire survey.

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women. METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively. RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination. CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.

Prenatal asfotase alfa-mediated enzyme replacement therapy restores delayed calcification in a severe infantile form of hypophosphatasia model mice.

Hypophosphatasia (HPP) is a congenital disorder caused by mutations in the tissue-nonspecific alkaline phosphatase (TNALP) gene. The pathogenesis of HPP varies, ranging from severe cases in which there is total absence of fetal bone calcification, which leads to stillbirth, to relatively mild cases in which the effects are confined to the teeth, such as early loss of the primary teeth. In recent years, the establishment of enzyme supplementation as a treatment method has prolonged survival in patients; however, this approach does not provide sufficient improvement for failed calcification. Furthermore, the effects of enzyme replacement therapy on the jawbone and periodontal tissues have not yet been studied in detail. Therefore, in this study, we investigated the therapeutic effects of enzyme replacement therapy on jawbone hypocalcification in mice. Recombinant TNALP was administered to mothers before birth and newborns immediately after birth, and the effect of treatment was evaluated at 20 days of age. The treated HPP mice had improved mandible (mandibular length and bone quality) and tooth quality (root length of mandibular first molar, formation of cementum), as well as improved periodontal tissue structure (structure of periodontal ligament). Furthermore, prenatal treatment had an additional therapeutic effect on the degree of mandible and enamel calcification. These results suggest that enzyme replacement therapy is effective for the treatment of HPP, specifically in the maxillofacial region (including the teeth and mandible), and that early initiation of treatment may have additional beneficial therapeutic effects.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology. Since 2012, the number of doctors in Japan who specialize in obstetrics and gynecology has shown a decreasing trend. To increase the number of doctors majoring in obstetrics and gynecology, the Japanese Trainees in Obstetrics and Gynecology subcommittee developed a new recruitment event called Welcome to OBGYN World! (WOW!); the aim of this event was to focus on lower grades of medical students. The present report describes the content of WOW! and the results of a post-event questionnaire administered to participating students and tutors. WOW! was held online in order to avoid the risk of Coronavirus Disease 2019 infection for participants. Sixty of the 82 medical schools nationwide (73.2%) participated in this event. Overall, there were 285 participating students, ranging from first to fourth grade in medical school, and 106 tutors were involved to teach material at the event. In the post-event questionnaire survey, 97.6% (248/254) and 100% of the participants stated they now had a high degree of interest in obstetrics and gynecology and found the specialty attractive, respectively. Furthermore, 93.6% (90/94) of the tutors stated that WOW! had helped recruitment activities in their universities. Based on this outcome, members of the Japanese Trainees of Obstetrics and Gynecology subcommittee will now try to increase the number of doctors specializing in obstetrics and gynecology by holding WOW! annually.

Association of online activities with obstetrics and gynecology specialty choice: a nationwide online survey.

Objectives: To investigate the association between online activities and the number of new obstetrics and gynecology senior residents. Methods: A nationwide web-based, self-administered anonymous survey was conducted to investigate recruitment and clerkship activities during the coronavirus disease 2019 pandemic. An online questionnaire was sent to 576 obstetrics and gynecology training institutions in Japan between December 21, 2020, and January 31, 2021. Overall, 334 institutions that gave valid responses were included (response rate: 58.0%). Multivariate logistic regression analysis examined the association between online activities, including recruitment and clerkship activities, and the number of new obstetrics and gynecology senior residents in 2021. The stratified analysis by implementing face-to-face activities was conducted to clarify the association. Results: The number of new senior residents increased in 187 facilities (56.0%) and decreased in 147 facilities (44.0%). The facilities that implemented face-to-face and online activities were 185 (55.4%) and 120 (35.9%), respectively. In multivariate logistic regression analysis, an increased number of new obstetrics and gynecology senior residents was significantly associated with face-to-face activities (adjusted odds ratio (AOR)=2.58, 95% confidence interval (CI): 1.11-5.97, p<.001) but not with online activities. In the stratified analysis, online activities were significantly associated with an increased number of new obstetrics and gynecology senior residents among the facilities without face-to-face activities (AOR=3.81, 95% CI: 1.40-10.32, p=.009) but not among those with face-to-face activities (AOR=0.87, 95% CI: 0.42-1.78). Conclusions: Online activities were associated with an increased number of new obstetrics and gynecology senior residents among the facilities that did not conduct face-to-face activities.

Prenatal enzyme replacement therapy for Akp2 -/- mice with lethal hypophosphatasia.

Hypophosphatasia (HPP) is a congenital skeletal disease. Impairment of bone mineralization and seizures are due to a deficiency of tissue-nonspecific alkaline phosphatase (TNAP). Enzyme replacement therapy (ERT) is available as a highly successful treatment for pediatric-onset HPP. However, the potential for prenatal ERT has not been fully investigated to date. In this study, we assessed outcomes and maternal safety using a combinational approach with prenatal and postnatal administration of recombinant TNAP in Akp2 -/- mice as a model of infantile HPP. For the prenatal ERT, we administered subcutaneous injections of recombinant TNAP to pregnant mice from embryonic day 11.5-14.5 until delivery, and then sequentially to Akp2 -/- pups from birth to day 18. For the postnatal ERT, we injected Akp2 -/- pups from birth until day 18. Prenatal ERT did not cause any ectopic mineralization in heterozygous maternal mice. Both prenatal and postnatal ERT preserved growth, survival rate and improved bone calcification in Akp2 -/- mice. However, the effects of additional prenatal treatment to newborn mice appeared to be minimal, and the difference between prenatal and postnatal ERT was subtle. Further improvement of the prenatal ERT schedule and long-term observation will be required. The present paper sets a standard for such future studies.

Alteration of circulating cell-free DNA level by external cephalic version: A potential biomarker for direct evaluation of placental damage.

AIM: To confirm that variations in cell-free fetal DNA (cffDNA) are indicators of external placental damage, we quantitatively investigated cffDNA alterations in maternal peripheral blood during external cephalic version (ECV). METHODS: We recruited 48 singleton pregnant women who underwent ECV in our hospital. Before and immediately after ECV, we harvested 10 ml of maternal peripheral blood samples for cffDNA analysis. cffDNA alterations were assessed based on the fetal fraction (FF) rate. We performed ECV without epidural anesthesia but administered epidural anesthesia if ECV was disrupted due to severe pain. RESULTS: The FF increased from 22.9% ± 5.7% to 27.0% ± 5.7% (p < 0.05) after ECV. The FF increased in both successful (before, 24.4% ± 5.9%; after, 28.1% ± 5.9%; p < 0.05) and unsuccessful (before, 21.8% ± 3.8%; after, 27.3% ± 4.2%; p < 0.05) cases, as well as in patients who received epidural anesthesia (before, 23.9% ± 4.7%; after, 28.5% ± 4.4%; p < 0.05) or underwent ECV more than once (before, 23.5% ± 6.1%; after, 28.4% ± 5.3%; p < 0.05). CONCLUSIONS: FF alterations increased due to external stresses during ECV; the alterations were markedly greater when the strength and duration of external stress increased. These FF alterations may serve as potential biomarkers for the direct assessment of placental damage.

Safety assessment of the prophylactic use of silicone gel sheets (Lady Care®) for the prevention of hypertrophic scars following caesarean section.

This study aimed to investigate the side effects of silicone gel sheet (Lady Care®) and evaluate its prophylactic efficacy in preventing abnormal scarring. Sixty women who underwent caesarean section were recruited from September 2016 to September 2017 in this prospective study. Lady Care® was applied from the 2nd to the 6th postoperative months. Side effects of Lady Care® were evaluated through medical examinations and questionnaires. A plastic surgeon diagnosed abnormal scarring. Pruritus was diagnosed in 25 (47.2%) patients; folliculitis, four (7.5%); dry skin, four (7.5%); contact dermatitis, three (5.7%); wound infection, two (3.8%); and epidermolysis, one (1.9%), albeit with mild severity. Following Lady Care® application, no abnormal scarring and mild hypertrophic scarring was observed in 32 (64.0%) and 18 (36.0%) patients respectively. Of seven patients with pre-existing hypertrophic scars, only two showed hypertrophic scarring after Lady Care® application. Our findings support the safety and prophylactic efficacy of Lady Care®.Impact StatementWhat is already known on this subject? The incidence of abnormal scarring, i.e. keloid or hypertrophic scar formation after caesarean section (CS) is reported to be ∼41%. Abnormal or excessive scar formation can lead to functional limitations, pruritus, pain and cosmetic issues. Studies have also shown a prophylactic effect of the application of silicone materials against the development of hypertrophic and keloid scars, though prohibitive cost and lack of adhesiveness of such gel sheets are known factors limiting their usage.What the results of this study add? The new silicone gel sheet 'Lady Care®' has strong adhesive properties and is consequently not easily peeled off. Furthermore, it is easy to use and economically efficient.What the implications are of these findings for clinical practice and/or further research? This is the first clinical trial on the application of Lady Care® silicone gel sheet for the prevention of CS scarring. Our findings support the safety and prophylactic efficacy of Lady Care®.

Amnion-derived cells as a reliable resource for next-generation regenerative medicine.

The placenta is composed of the amnion, chorionic plate, villous and smooth chorion, decidua basalis, and umbilical cord. The amnion is a readily obtainable source of a large number of cells and cell types, including epithelium, mesenchyme, and endothelium, and is thus an allogeneic resource for regenerative medicine. Endothelial cells are obtained from large arteries and veins in the amniotic membrane as well as the umbilical cord. The amnion-derived cells exhibit transdifferentiation capabilities, including chondrogenesis and cardiomyogenesis, by introduction of transcription factors, in addition to their original and potential phenotypes. The amnion is also a source for production of induced pluripotent stem cells (AM-iPSCs). The AM-iPSCs exhibit stable phenotypes, such as multipotency and immortality, and a unique gene expression pattern. Through the use of amnion-derived cells, as well as other placenta-derived cells, preclinical proof of concept has been achieved in a mouse model of muscular dystrophy.

Characterization of a Small Supernumerary Marker Chromosome Derived from Xq28 and 14q11.2 Detected Prenatally.

We present the characterization of a case with a small supernumerary marker chromosome (sSMC) detected prenatally derived from Xq28 and 14q11.2 maternal translocation. A 33-year-old Japanese woman, primigravida, underwent amniocentesis because of fetal growth restriction and fetal structural abnormality at 30 weeks of gestation. The fetal karyotype was identified as 47,XY,+mar. Additionally, the single nucleotide polymorphism array analysis revealed copy number gains at Xq28 and 14q11.2. A male infant, weighing 1,391 g, was delivered at term by cesarean section. Maternal and paternal karyotypes were 46,X,t(X; 14)(q28; q11) and 46,XY, respectively. These findings indicated that the sSMC might have originated from chromosome disjunction at a ratio of three to one. Here we describe a case with an sSMC derived from Xq28 and 14q11.2. Our findings suggest that this sSMC is most likely pathogenic. The collection of additional cases may be required.

The Cytoreductive Effect of Radiotherapy for Small Cell Ovarian Carcinoma of the Pulmonary Type: A Case Report and Review of the Literature.

Small cell ovarian carcinoma of the pulmonary type is a rare and highly aggressive tumor for which a suitable treatment strategy has not been established. A 45-year-old woman presented with abdominal swelling, and primary ovarian carcinoma was suspected. The postoperative pathological diagnosis was small cell ovarian carcinoma of the pulmonary type. She also had complicated grade 1 endometrioid carcinoma of the uterine corpus. Three courses of cisplatin and etoposide therapy were administered as adjuvant chemotherapy. Because the tumor was chemotherapy resistant, she underwent palliative abdominal irradiation at a dose of 26 Gy in 13 fractions, which induced cytoreduction and provided symptomatic relief. She died 4 months after surgery. Lactate dehydrogenase was a useful tumor marker during treatment. Here, we present an extremely rare case of a patient with small cell ovarian carcinoma of the pulmonary type treated with radiotherapy after surgery and chemotherapy.

Continuous fetal head flexion as a marker for prenatal diagnosis of lethal multiple pterygium syndrome: a case report.

Lethal multiple pterygium syndrome (LMPS) is a fatal hereditary disease associated with abnormalities such as pterygium-induced congenital contractures. Fetal hydrops is present in more than half of all patients with LMPS, and all patients with LMPS are either stillborn or die in the early neonatal period. Ultrasonography findings for the prenatal diagnosis of LMPS include the detection of cutaneous webbing at multiple joints, multiple joint contractures, absent limb movement, and increased nuchal translucency. Here, we describe a patient who was diagnosed as having LMPS due to continuous fetal head flexion, despite the absence of the usual characteristics of the condition, including pterygium at the joints. Thus, continuous fetal head flexion can be a useful marker for prenatally diagnosing LMPS.

Clinical course of disseminated intravascular coagulopathy-type amniotic fluid embolism: A report of three cases.

Amniotic fluid embolism (AFE) is a rare complication of pregnancy and its mortality rate is high. There have been few reports of AFE with presence of severe coagulopathy and incoagulable bleeding, and absence of cardiopulmonary symptoms or limited cardiopulmonary symptoms, followed by massive blood loss during delivery. Such cases have been referred to as disseminated intravascular coagulopathy-type AFE, and the characteristics of this condition have been presented previously. Here we report three cases that fulfilled the diagnostic characteristics of disseminated intravascular coagulopathy-type AFE.

Crucial role for CD69 in the pathogenesis of dextran sulphate sodium-induced colitis.

CD69 is a membrane molecule transiently expressed on activated lymphocytes, and its selective expression in inflammatory infiltrates suggests that it plays a role in the pathogenesis of inflammatory diseases. In this study, we used CD69-deficient (CD69 KO) mice to assess the role of CD69 in the pathogenesis of dextran sulphate sodium (DSS)-induced acute and chronic colitis. The severity of colitis was assessed by the survival rate, clinical signs, colon length, histological examination and the expression of cytokines and chemokines in the large intestines. Both acute and chronic colitis were attenuated in the CD69 KO mice, as reflected by the lower lethality, weight loss, clinical signs, and improved histological findings. CD69(+) cells infiltrated extensively into the inflamed mucosa of the colon in WT mice after DSS treatment. Experiments with the transfer of WT CD4 T cells into CD69 KO mice restored the induction of colitis. The administration of an anti-CD69 antibody also inhibited the induction of the DSS-induced colitis. These results indicate that CD69 expressed on CD4 T cells plays an important role in the pathogenesis of DSS-induced acute and chronic colitis, and that CD69 could be a possible therapeutic target for colitis.

Complete genome sequence of NBRC 3288, a unique cellulose-nonproducing strain of Gluconacetobacter xylinus isolated from vinegar.

Gluconacetobacter xylinus is involved in the industrial production of cellulose. We have determined the genome sequence of G. xylinus NBRC 3288, a cellulose-nonproducing strain. Comparative analysis of genomes of G. xylinus NBRC 3288 with those of the cellulose-producing strains clarified the genes important for cellulose production in Gluconacetobacter.

Comparison of cancer-cell seeding, viability and deformation in the lung, muscle and liver, visualized by subcellular real-time imaging in the live mouse.

The comparison of cancer cell seeding, deformation and viability in the lung, muscle and liver of nude mice in real-time is reported here. The mice were intubated to support ventilation with positive end-respiratory pressure (PEEP) for imaging on the lung. Human fibrosarcoma cells with green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm (dual-color HT-1080 cells) were injected into the tail vein for lung imaging, the portal vein for liver imaging or the abdominal aorta for muscle imaging which was performed with an Olympus OV100 Small Animal Imaging System. The length of the cytoplasm and nuclei in 20 seeded cancer cells were measured. A large number of cells initially arrested in the lung capillaries and many cells formed aggregates. The cell number decreased rapidly at 6 and 24 h. There was no significant difference in cancer cell survival when immunocompetent C57BL/6 mice were used in place of the nude mice, suggesting that T cell reaction is not very important in the first 24 h after seeding of cancer cells in the lung. In the lung and liver, little cancer cell deformation occurred. In contrast in the muscle, the cytoplasm and nuclei of the seeded cells were highly deformed and many fragmented cells were observed. The rate of cancer cell death was highest in the lung and lowest in the muscle. In each organ, single disseminated cells tended to die earlier than aggregated cells. The results of this study suggest that the early steps of metastasis are different in the lung, liver and muscle.