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Background: The role of barbed sutures in preventing myometrial defects and enhancing postpartum outcomes after cesarean section (C-section) is uncertain., Objective: This study compared clinical and ultrasonographic outcomes of uterine scar defects after C-section with barbed and conventional smooth thread sutures., Study Design: This was a multicenter, parallel-group, randomized, controlled clinical trial. Four obstetrics and gynecology departments across three Japanese healthcare regions were included. The participants were women requiring their first cesarean delivery between May 2020 and March 2023. Of the 1211 participants enrolled, 298 underwent C-section and 253 were followed up until July 2023. Participants with singleton pregnancies were randomly assigned (1:1 ratio) to receive either conventional or spiral thread sutures with a double-layer continuous suture. The study period comprised the time of consent to the 6- to 7-month examination. The primary endpoint was the rate of scar niches >2 mm evaluated using transvaginal ultrasonography at 6 to 7 months after surgery. Additional metrics included the total operative time, suture application time, operative blood loss, number of additional sutures required for hemostasis, maternal surgical complications, postoperative infections, surgeon's years of experience, and individual subscale scores., Results: All data of the 220 participants (barbed suture group: 110; conventional suture group: 110) were available, thus enabling a full analysis set. A comparison of the barbed and conventional suture groups, respectively, revealed the following: niche length, 2.45±1.65 mm (range: 1.0-6.7) vs 3.79±1.84 mm (range: 1.0-11.0) (P<.001); niche depth, 1.78±1.07 mm (range: 1.0-5.7) vs 2.70±1.34 mm (range: 1.0-7.3) (P<.001); residual myometrial thickness (RMT), 8.46±1.74 mm (range: 4.8-13.0) vs 7.07±2.186 mm (range: 2.2-16.2) (P<.001); and niche width, 1.58±2.73 mm (range: 0.0-14.0) vs 2.88±2.36 mm (range: 0.0-11.0) (P<.001), respectively. The barbed suture group exhibited no defects and an RMT <3 mm. Furthermore, the barbed suture group had a lower rate of uterine niches (29.1%; n=32/110) than the conventional suture group (68.2%; n=75/110). Secondary outcomes showed no significant differences in operative times, maternal surgical complications, or postoperative complications., Conclusion: Double-layer barbed sutures during cesarean delivery may prevent C-section scar defects and postoperative complications. El resumen está disponible en Español al final del artículo., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Understanding background factors is beneficial for interpreting general movements (GMs). This study examines the factors involved in preterm-writhing GMs by comparing twins and singletons., Method: The subjects were 107 infants cared for at Oita University. The cohort consisted of very-low-birth-weight infants, including twins with a birth weight < 2000 g. The median gestational age (GA) was 29 weeks 1 day. The subjects consisted of 75 singletons, 32 twins (16 pairs), 20 monochorionic twins (M-twins), and 12 dichorionic twins (D-twins). GMs were scored according to the GMs optimality score (GMOS) and integrated into 6 items: the quality, neck-trunk and space, amplitude-speed, rotation, onset-offset and cramped, and tremulous score at 32-34 weeks, 35-36 weeks, and 37-42 weeks' GA. A hierarchical cluster analysis was performed using integrated GMOS, and the characteristics of clusters were examined according to clinical backgrounds., Results: Three clusters were identified. Cluster 1 was characterized by good-quality GMs, cluster 2 by a poor repertoire but optimal space and rotatory components, and cluster 3 by overall poor-quality GMs, respectively. The mean GMOSs were 36.6, 31.8 and 24.3 in clusters 1, 2, and 3, respectively. There were no marked differences in proportions within clusters with respect to sex and twins. Small-for-gestational age (SGA) was significantly more frequent in cluster 3 at 32-34 weeks' GA than in other clusters. Perinatal brain injury had a significantly lower proportion in cluster 1 and a higher proportion in cluster 3 at 35-36 weeks' GA and 37-42 weeks' GA. M-twin pairs tended to belong to the same clusters at 35-36 weeks' GA., Conclusion: Preterm writhing GMs are associated with SGA and perinatal brain injury. Cluster matching in M-twins suggests that certain genetic factors may substantially influence GMs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

During the coronavirus pandemic, face-to-face simulation education became impossible. Therefore, we aimed to develop remote-access simulation education with a sense of realism through Information and Communication Technology (ICT) using a perinatal whole-body management and delivery simulator. In September 2021, we administered a multi-center simultaneous remote simulation based on our developed model. Ten universities in the Chugoku-Shikoku region were connected via a web-conferencing system to a live broadcast of a virtual vaginal birth in which a fictional hospitalized pregnant woman experienced accelerated labor and gave birth through vacuum delivery for fetal distress. A Video on Demand (VOD) was made beforehand using a new simulator that allowed for a visual understanding of the process of the inter-vaginal examination. We provided a participatory program that enhanced the sense of realism by combining VOD and real-time lectures on each scenario, with two-way communication between participants and trainee doctors using a chat function. Most participants answered "satisfied" or "very satisfied" with the content, level of difficulty, and level of understanding. From November 2021, we have used the videos of all processes in face-to-face classes. Our construction of a high-flexibility education system using remote simulation in the field of obstetrics and gynecology, especially in the vaginal delivery module, is unique, creative, and sustainable., Competing Interests: No potential conflict of interest relevant to this article was reported.

Introduction: Chorioamnionitis (CAM) involves infection and inflammation of the chorion and amniotic membrane, but there are still no effective diagnostic biomarkers for CAM., Methods: We investigated the correlation between RNA editing enzyme Adenosine deaminase family acting on RNA 1 (ADAR1) and CAM in chorion and amniotic membrane specimens derived from premature rupture of the membrane (PROM), CAM (pathologically diagnosed), and clinical CAM (clinically diagnosed) patients using reverse transcription polymerase chain reaction (RT-PCR)., Results: ADAR1 was upregulated in the chorion and amniotic membrane specimens of CAM and clinical CAM patients (p < 0.001 and p = 0.005). ADAR1 had a significantly higher area under the curve (AUC) (0.735 and 0.828) than markers of inflammation characteristics in diagnosing CAM and clinical CAM patients. ADAR1 also had significantly higher AUC (0.701 and 0.837) than clinical characteristics for CAM and clinical CAM patients., Discussion: ADAR1 can be a useful diagnostic biomarker in CAM patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Since July 2022, obstetrical disseminated intravascular coagulation (DIC) in Japan has been diagnosed based on the new criteria (tentative version), which assesses the main underlying disease, fibrinogen level, and fibrin/fibrinogen degradation products or D-dimer level. In June 2024, the tentative version underwent minor revision and the final version was released. The previous Japanese criteria assessed underlying disease, clinical symptoms, and various laboratory findings. This study aimed to prove the effectiveness, reliability, and validity of the new criteria (final version). We analyzed 212 women with singleton pregnancies who delivered after 22 gestational weeks and experienced blood loss ≥ 1000 mL during vaginal delivery or ≥ 2000 mL during cesarean section. Those with missing laboratory findings before receiving blood transfusion at delivery were excluded. In the obstetrical DIC group, the frequency of fibrinogen levels < 150 mg/dL was significantly higher than in the control group (90% vs. 5%, p < 0.0001), as was the frequency of scores ≥ 8 according to the previous Japanese criteria (100% vs. 10%, p < 0.0001). Cronbach alpha was 0.757 and Spearman's rank-order correlation was 0.558 between the new and previous criteria. In conclusion, we proved the effectiveness, reliability, and validity of the Japanese new criteria (final version) to diagnose obstetrical DIC., (© 2024. The Author(s).)

Pregnant women and individuals with sickle cell trait (SCT) and underlying comorbidities are both independently more vulnerable to severe illness from coronavirus disease 2019 (COVID-19) compared to nonpregnant women and those without SCT. However, our understanding of the specific factors influencing susceptibility to COVID-19 infection among pregnant women with SCT is currently constrained by limited available data. This study aims to determine the risk and protective factors that influence the likelihood of COVID-19 infection in this population. A retrospective analysis was done among 151 women with SCT in the reproductive age group. Multivariable analysis was performed to determine the various factors affecting COVID-19 infection among pregnant women with SCT. The study found that COVID-19-vaccinated pregnant women with SCT had a 90% lower risk of contracting COVID-19 and were 9 times more likely to have a COVID-19 infection if they had a history of pulmonary conditions such as asthma or chronic obstructive pulmonary disease. The present study further emphasizes the importance of the COVID-19 vaccine in preventing infection and safeguarding the health of pregnant women with SCT, particularly those with underlying comorbidities., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Kim Abbegail Tan Aldecoa et al.)

We investigated the effectiveness of simulation-based education in Focused Assessment with Sonography for Trauma (FAST) to increase the number of Emergency Medical Technicians (EMTs) capable of performing ultrasound examinations in vehicles under the guidance of a physician. Twenty-eight paramedics watched a 14-min video on the features of the ultrasound system, its use, and the scanning method for each part of the body. Each participant performed four FAST examinations using a portable ultrasound device, and the task performance was rated using the Task Specific Checklist (TSC) and Global Rating Scale (GRS). The time required for visualizing each examination site and each FAST was assessed. The mean time required for the first and fourth FAST was 144.6 ± 52.4 s and 90.5 ± 31.0 s, respectively. The time required for each test significantly decreased with repeated testing (p < 0.001). The time to complete FAST was significantly shortened for the pericardial cavity (33.4 ± 23.1/15.3 ± 10.6 s, p < 0.01), right thoracic cavity (25.2 ± 11.8/12.1 ± 8.3 s, p < 0.01), Morrison fossa (19.1 ± 10.8/10.8 ± 6.3 s, p < 0.05), and left thoracic cavity (19.0 ± 8.3/15.6 ± 8.3 s, p < 0.05). TSC and GRS scores were elevated, and all EMTs could obtain valid images. The combination of a brief video lecture and hands-on training significantly reduced the time required for FAST performance. Moreover, repeated practice enabled the EMTs to efficiently obtain accurate and clinically useful images., (© 2024. The Author(s).)

Objective: To investigate the incidence and risk factors of small-for-gestational age (SGA) short stature at 2 and 3 years of age in SGA offspring born to women with hypertensive disorders of pregnancy (HDP)., Methods: We examined 226 women with HDP whose respective SGA offspring were delivered., Results: Eighty offspring (41.2%) were diagnosed with SGA short stature. The prematurity before 32 weeks of gestation was the most significant factor for catch-up growth failure., Conclusion: In SGA offspring born to women with HDP, SGA short stature incidence was high, and the risk factor was prematurity before 32 weeks of gestation.

Introduction: Preeclampsia (PE) pathogenesis is explained by the two-stage disorder theory. However, mechanisms underlying hypertension and proteinuria in PE remain unclear. The role of (pro)renin receptor (PRR) in PE pathology has received special attention. We examined endothelin-1 (ET-1) production via placental PRR in a PE mouse model., Methods: At 14.5 day-post-coitum (DPC), we performed a reduced uterine perfusion pressure (RUPP) operation, ligating the uterine arteriovenous vessels in female mice. We also infused these mice with a PRR inhibitor, decoy peptide in the handle region of prorenin (HRP) for mice (NH2-RIPLKKMPSV-COOH). At 18.5 DPC, blood, urine, and placenta were collected; fetus and placenta were weighed. We evaluated placental hypoxia using quantitative polymerase chain reaction (PCR), with hypoxia-inducible factor-1α (HIF-1α) as index. We also evaluated PRR, transforming growth factor-β1 (TGF-β1), and ET-1 expression in the placenta using quantitative PCR and western blotting. ET-1 concentration in blood plasma was assessed using enzyme-linked immunosorbent assay., Results: Blood pressure and proteinuria significantly increased, and fetal and placental weights decreased in RUPP mice. HIF-1α, PRR, TGF-β1, and ET-1 expressions considerably increased in RUPP mice placentas. ET-1 concentration in RUPP mice blood plasma was markedly increased. PRR inhibitor suppressed these changes., Discussion: In PE model mice that underwent RUPP treatment, placental hypoxia increased PRR and ET-1 expression suggesting a causative relationship between ET-1 and intracellular PRR signaling. RUPP treatment, when combined with HRP, reversed the effect of elevated ET-1 levels in the model. This study may help to elucidate the pathogenesis of PE considering PRR and ET-1., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Knee osteoarthritis (KOA) is highly prevalent in older women, and previous studies suggest the involvement of hormonal factors play a role in the pathogenesis of osteoarthritis. KOA causes musculoskeletal impairment, resulting in decreased physical activity, muscle mass, and strength, which leads to sarcopenia and further increases the burden on healthcare systems. Oestrogen replacement therapy (ERT) improves joint pain and muscle performance in early menopausal women. Muscle resistance exercise (MRE) is a non-pharmacological method that preserves the physical functions of patients with KOA. However, data on short-term oestrogen administration combined with MRE in postmenopausal women, especially in those aged > 65 years, are limited. Therefore, this study presents a protocol of a trial aimed to examine the synergistic effect of ERT and MRE on lower-limb physical performance in older women with KOA., Methods: We will conduct a double-blinded, randomised placebo-controlled trial in 80 Japanese women aged > 65 years living independently with knee pain. The participants will be randomly categorised into two groups: (1) 12-week MRE programme with transdermal oestrogen gel containing 0.54 mg oestradiol per push and (2) 12-week MRE programme with placebo gel. The primary outcome measured using the 30-s chair stand test, and secondary outcomes (body composition, lower-limb muscle strength, physical performance, self-reported measure of knee pain, and quality of life) will be measured at baseline, 3 months, and 12 months, and these outcomes will be analysed based on the intention-to-treat., Discussion: The EPOK trial is the first study to focus on the efficacy of ERT on MRE among women aged > 65 years with KOA. This trial will provide an effective MRE to prevent KOA-induced lower-limb muscle weakness, confirming the benefit of short-term oestrogen administration., Trial Registration: Japan Registry of Clinical Trials: jRCTs061210062. Registered 17th December 2021, https://jrct.niph.go.jp/en-latest-detail/jRCTs061210062 ., (© 2023. The Author(s).)

Video recording and editing of general movements (GMs) takes time. We devised an algorithm to automatically extract the period of GMs emergence to assist in the assessment of GMs. The algorithm consisted of δHR: subtracting the moving average heart rate (HR) for the past 60 s from the average instantaneous HR; and %δHR: the percentage of the instantaneous HR to the moving average HR. Ten-second sections in which δHR was positive for three consecutive sections and contained at least one section with %δHR > 105% were extracted. Extracted periods are called automated extraction sections (AESs). We evaluated the concordance rate between AESs and GMs in three periods (gestational age 24−32, 33−34, and 35−36 weeks). The records of 84 very low birth weight infants were evaluated. Approximately 90% of AESs were accompanied by GMs at any period in both the supine and prone positions. The proportion of full-course (beginning to end) GMs among GMs in the AES was 80−85% in the supine position and 90% in the prone position in all periods. We could extract a sufficient number of assessable GMs with this algorithm, which is expected to be widely used for assisting in the assessment of GMs.

This study aimed to develop a simplified model for predicting end-stage kidney disease (ESKD) in patients with diabetes. The cohort included 2549 individuals who were followed up at Kyushu University Hospital (Japan) between January 1, 2008 and December 31, 2018. The outcome was a composite of ESKD, defined as an eGFR < 15 mL min -1 [1.73 m] -2 , dialysis, or renal transplantation. The mean follow-up was 5.6 [Formula: see text] 3.7 years, and ESKD occurred in 176 (6.2%) individuals. Both a machine learning random forest model and a Cox proportional hazard model selected eGFR, proteinuria, hemoglobin A1c, serum albumin levels, and serum bilirubin levels in a descending order as the most important predictors among 20 baseline variables. A model using eGFR, proteinuria and hemoglobin A1c showed a relatively good performance in discrimination (C-statistic: 0.842) and calibration (Nam and D'Agostino [Formula: see text] 2 statistic: 22.4). Adding serum albumin and bilirubin levels to the model further improved it, and a model using 5 variables showed the best performance in the predictive ability (C-statistic: 0.895, [Formula: see text] 2 statistic: 7.7). The accuracy of this model was validated in an external cohort (n = 5153). This novel simplified prediction model may be clinically useful for predicting ESKD in patients with diabetes., (© 2022. The Author(s).)

Objective: Previous reports have demonstrated the association of serum bilirubin levels with the progression of diabetic nephropathy. The objective of this study is to assess the association of basal bilirubin levels with progressive renal decline (PRD) and end-stage kidney disease (ESKD)., Methods: A total of 298 patients with diabetes who visited Kyushu University Hospital (Japan) were recruited and followed up for 10 years. PRD was defined as a negative change in estimated glomerular filtration ratio (eGFR) >3.7%/year, 2.5th percentile. Logistic regression analysis was performed to evaluate the association of total bilirubin levels with PRD and its cut-off point was determined by receiver operating characteristic (ROC) analysis. Kaplan-Meier method and Cox hazard regression analysis were used to evaluate the predictive ability of its cut-off point for ESKD., Results: Logistic regression model showed that total bilirubin levels were significantly associated with PRD, and ROC analysis showed that its cut-off point was 0.5 mg/dL. Kaplan-Meier method showed that the percent of patients who reached two endpoints, composite endpoint (ESKD or doubling of creatinine level) or 30% eGFR decline, was significantly higher in the low bilirubin group than in the high bilirubin group (18.5% vs 11.0%, P = 0.045; 49.1% vs 42.1%, P = 0.045, respectively, log-rank test). Cox hazard regression models confirmed the independence of the predictive ability of its cut-off point., Conclusions: Serum total bilirubin levels were negatively associated with PRD in diabetic nephropathy and its cut-off point was 0.5 mg/dL. It may be clinically useful for identifying patients at high risk of ESKD., Competing Interests: The authors have declared that no competing interests exist.

Background: Cases of uterine wall thinning and placental abnormalities complicated with systemic lupus erythematosus (SLE) during pregnancy have been reported in Asian countries for ten years. Long-term steroid use can cause muscle degeneration, but the mechanism of myometrium thinning was not known. Through the review of published articles, this report is the first review of cases to discuss the pathogenesis and clinical features of thinned myometrium and placenta accreta spectrum (PAS) in pregnant patients with SLE., Case Presentation: A twenty-nine-year-old primigravida with a history of lupus enteritis and paralytic ileus had a natural conception after less than two years of steroid treatment. An ultrasonographic study showed a thin uterine wall with a widespread thick placenta on the entire surface of the uterine cavity in the third trimester. At the 39th gestational week, she underwent a cesarean section due to the failure of the uterus to contract, even though the injection of oxytocin. There were several engorged vessels on the surface of the anterior uterine wall at the time of laparotomy. We decided to perform a hysterectomy because diffuse PAS replaced her uterus., Conclusion: A review of reported cases and our case shows an unusual complication of SLE that might be related to the particular condition of the estrogen-mediated immune system. Clinicians should always pay attention to the possibility of uterine wall thinning as uterine atony and the structural abnormality of the placenta for SLE patients with the unscarred uterus., (© 2022. The Author(s).)

Polycystic ovary syndrome (PCOS) is a common endocrine metabolic disorder that is associated with high insulin resistance and obesity. However, ~70% of women with PCOS in Japan are non-obese. We retrospectively analyzed the cases of 163 Japanese women with PCOS who visited our Ob/Gyn department in 2006-2018 to determine which has a greater effect on insulin resistance: PCOS or obesity. We reviewed the women's medical records and calculated their insulin resistance and insulin secretion. The women's mean age and pre-pregnancy body mass index (BMI) were 30±5.8 years and 24.8±5.6 kg/m2, respectively; their mean ± SD fasting plasma glucose, 94.1±13.7 mg/dL; HOMA-IR, 2.1±2.0; QUICKI, 0.4±0.0; and HOMA-β, 108.9±88.0%. Sixtyeight women were pregnant, and 37% (n=25) were obese (BMI ≥ 25 kg/m2). Obesity had a greater effect on insulin resistance: fasting plasma glucose F(1, 53)=6.134, p<0.05; fasting insulin F(1, 53)=31.606, p<0.01; HOMA-IR F(1, 53)=31.670, p<0.01; QUICKI F(1, 53)=16.156, p<0.01. There was no significant difference in values other than QUICKI and testosterone between the women with and without PCOS. Obesity thus had a greater effect on increased insulin resistance in pregnant women with PCOS. Further studies of the insulin resistance of non-obese women with PCOS is needed, as non-obese women with PCOS are common in Asia., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Although the side effects of cancer chemotherapy impair a patient's quality of life, family members' awareness of side effects may relieve patient anxiety and distress., Aim: We investigated whether patients and their families were consistent in recognizing the occurrence and severity of symptomatic side effects of chemotherapy treatment for cancer., Methods and Results: This was a prospective observational study. We administered a questionnaire survey to patients and family members to assess the frequency of occurrence (1: never, 2: almost never, 3: sometimes, 4: frequently, 5: almost always, 6: unknown) and the degree of severity (1: mild, 2: moderate, 3: severe, 4: extremely severe, 5: unknown) of physical and psychological symptoms associated with cancer chemotherapy. Weighted Kappa and Cramer coefficients were used to assess consistency between the two groups. We surveyed 20 pairs of patients (5 men, 15 women) and their families (10 men, 10 women); 17 pairs lived together. The median age was 65.5 years (interquartile [IQR], 58.75, 69.25) for patients and 61.00 years (IQR, 47.25, 71.25) for family members. Of patients, 17 had solid cancer, and three had leukemia. Family members mostly recognized objectively visible symptoms such as hair loss and development of spots and keratinization. However, it was difficult for families to detect invisible subjective symptoms such as weakness, dysesthesia, depressed mood, and unarticulated anxiety., Conclusions: The results indicated that recognition of invisible subjective symptoms in patients undergoing chemotherapy was difficult even for family members. Therefore, a multidisciplinary approach in which various medical professionals actively communicate with both patients and families is important. Information sharing in collaboration with patients and families could increase understanding of the patient's condition and optimize patient care., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Extravillous trophoblast (EVT) invasion is important for embryo implantation, placental development, and successful remodeling of the uterine spiral artery. Endocrine gland derived-vascular endothelial growth factor (EG-VEGF) and matrix metalloproteinases (MMPs) are implicated in EVT invasion; however, the high con-centrations found in pregnancy pathologies have not been investigated in non-tumor trophoblasts. The roles of EG-VEGF, prokineticin receptors (PROKR1/2), MMP-2, and MMP-9 in EVT invasion during spiral artery remodeling were evaluated using human EVT from HTR-8/SVneo cell lines. The expression of MMP-2, MMP-9, and mitogen-activated protein kinase (MAPK), and Akt pathways in HTR-8/SVneo cells treated with recom-binant EG-VEGF alongside anti-PROKR1 and/or anti-PROKR2 antibodies was evaluated using quantitative reverse transcription-PCR and western blotting. Wound-healing and cell invasion assays were performed to assess the migration and invasion of these treated cells. Interestingly, 20 nM EG-VEGF activated ERK1/2 sig-naling and upregulated MMP-2 and MMP-9. This effect was suppressed by anti-PROKR2 antibody via ERK1/2 downregulation. Anti-PROKR2 antibody inhibited the migration and invasion of EG-VEGF-stimulated HTR-8/SVneo cells. Elevated concentrations of EG-VEGF enhance EVT invasion in a human trophoblast cell line by upregulating MMP-2 and MMP-9 via PROKR2. These new insights into the regulation of epithelial cell invasion may help in developing therapeutic interventions for placental-related diseases during pregnancy., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: The aim of this randomized controlled trial (RCT) is to investigate whether Spiral-thread sutures are superior to conventional sutures (0-Vicryl) for preventing uterine scar thinning following elective cesarean section., Methods: This multicenter, parallel-group RCT will be conducted in four hospitals across three medical regions in Japan to assess 200 women (≥20 years old) with singleton pregnancies who are scheduled to undergo cesarean sections. Eligible women will be randomly assigned (1:1 ratio) to receive either the conventional uterine suture continuous absorption thread, which is most commonly used in Japan, or the Spiral thread. The primary endpoint is the degree of scar thinning, measured by transvaginal ultrasonography 6-7 months postoperatively, to evaluate the position of the uterus (anterior or posterior tilt) and myometrial wound thickness. The degree of thinning will be compared between the groups, and four measurements (mm) of the thinning area, including caudal distance, depth of the depression, remaining thickness of the myometrium on the serous side of the most depressed area, and width of the depression, will be recorded in the sagittal view on transvaginal ultrasound. Secondary endpoints will include total operative time, suture application time (from birth to the end of uterine suturing), operative blood loss, number of additional Z-sutures or continuous sutures required to stop bleeding, maternal abnormality frequency (surgical complications and postoperative infections), surgeon's years of experience, and clinical interpretation of individual subscale scores., Discussion: This study shall provide important evidence on the optimal suture for preventing hysterotomy wound thinning after the first cesarean section., Trial Registration: National Institute of Public Health, Japan: jRCT1062200001 (May 7, 2020; https://rctportal.niph.go.jp/en/detail?trial&#95;id=jRCT1062200001) and Okayama University Certified Review Board: CRB6180001 (April 9, 2020, version 3.0)., (Copyright © 2021. Published by Elsevier Inc.)

Early diagnosis and therapy are important in a cesarean scar pregnancy (CSP), which can cause uterine rupture with resultant massive bleeding. However, there are some reports of CSPs continued to term. The optimal management of CSPs remains unclear; therefore, we investigated the clinical courses of CSPs diagnosed and treated at perinatal institutions in the Chugoku and Shikoku regions of Japan. We enrolled 60 women diag-nosed with CSP at 21 institutions from January 2006 to December 2015. Of the 60 women diagnosed with CSP, 57 were treated. Pregnancy was terminated in 48 women and continued in 9. Thirteen women underwent transabdominal hysterectomy; they experienced no postoperative complications or allogeneic blood transfu-sion. Nine women received therapies such as dilation and curettage, and 26 received non-surgical therapies such as methotrexate and topical administration of potassium chloride. Among 9 women who chose to con-tinue with their CSP, 7 successfully delivered newborns, 2 had uterine ruptures in the second trimester, and all women required transabdominal hysterectomy. Diagnosis and therapy in the first trimester of pregnancy are important in the management strategy of a CSP. When continuing a CSP, the risk of uterine rupture and trans-abdominal hysterectomy must be considered., Competing Interests: No potential conflict of interest relevant to this article was reported.

Objective: To retrospectively investigate cesarean scar pregnancy (CSP) patients who received systemic methotrexate (MTX) and to clarify the criteria for administering systemic MTX to CSP patients., Materials and Methods: Fifteen CSP patients who were initially treated with systemic MTX (50 mg/m 2 /week) were included. Nine patients, who needed a uterine artery embolization (UAE) or a laparotomy, including a transabdominal hysterectomy (TAH), were defined as the unsuccessful MTX group. Six patients who did not require UAE or a laparotomy were defined as the successful MTX group. Furthermore, the hCG cut-off value and the GS cut-off size at the time of CSP diagnosis, which differentiated successful and unsuccessful patients, were defined. MTX success rates were investigated by combining the hCG and gestational sac (GS) size cut-off values., Results: The hCG cut-off value was 17757.0 mIU/mL, and the GS cut-off size was 10.4 mm. In patients with hCG values less than 17757.0 mIU/mL, the MTX success rate was 75.0%. Fewer patients needed UAE or a laparotomy compared to patients with hCG values higher than 17757.0 mIU/mL (P = 0.007). In patients with a GS size less than 10.4 mm, the MTX success rate was 80.0%. Fewer patients among them needed UAE or a laparotomy compared to those among patients with a GS size greater than 10.4 mm (P = 0.089). In patients with hCG values and GS sizes lower than the cut-off values, the MTX success rate was 80.0%. Fewer patients among them needed UAE or a laparotomy compared to those among patients with hCG values and/or GS sizes higher than the cut-off values, respectively (P = 0.010)., Conclusion: Patients with hCG values less than 17757.0 mIU/mL and GS sizes less than 10.4 mm may have a greater chance of successful systemic MTX treatment when it is used as the first line of treatment for CSP., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier B.V.)

Background: Two-dimensional (2D) speckle tracking echography (STE) is a new diagnostic modality that allows for the assessment of myocardial deformation. The present study assessed the feasibility of fetal 2D-STE at a high frame rate and determined the reference values for left ventricular (LV)- and right ventricular (RV)- global longitudinal strain (GLS)., Methods: In this prospective study, 109 fetuses with gestational ages ranging from 18 to 38 weeks underwent 2D echocardiography between August 2018 and December 2019. All recordings were performed using the Aplio i800 (CANON Medical Systems Corporation, Tochigi, Japan) and a convex probe (4 MHz) for fetuses., Results: Longitudinal peak systolic strain measurements were obtained in 98 of 109 healthy fetuses (90%). All ultrasound videos were recorded with a median frame rate of 172 (range, 100-274) frames/s. The LV-GLS was almost constant, regardless of the number of weeks since the second trimester (r = -0.0087, p = ns). The RV-GLS decreased significantly with gestational age (r = 0.39, p < 0.01)., Conclusions: STE may be useful for quantifying the systolic myocardial function in a fetus., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An association between preeclampsia and (pro)renin was recently reported. Intracellular signaling of the (pro) renin receptor [(P)RR] increases the expressions of TGF-β and PAI-1. In this study we sought to clarify the involvement of (pro)renin in the pathogenesis of preeclampsia via the intracellular signaling of (P)RR on preeclampsia placentas. Activated (pro)renin plasma concentrations were compared between pregnant women with (n=15) and without (n=28) preeclampsia. The placentas were immunohistochemically evaluated with anti-HIF-1α and anti-(P)RR antibodies. HTR-8/SVneo cells were cultured under hypoxic conditions and treated with human recombinant (pro)renin. The mRNA expressions of HIF-1α, (P)RR, PAI-1, TGF-β, and ET-1 were also examined by real-time RCR. The activated (pro)renin plasma concentration was significantly higher in the third vs. the second trimester in the preeclampsia patients. HIF-1α and (P)RR expressions were significantly increased in the preeclampsia placentas. The mRNA expressions of PAI-1, TGF-β, and ET-1 were significantly increased in the experiments using recombinant (pro)renin vs. hypoxic conditions. (P)RR expression in preeclampsia placentas is increased by persistent hypoxia through the second and third trimesters, and PAI-1, TGF-β, and ET-1 production is increased via (P)RR. Our results suggest that ET-1 production via the intracellular signaling of (P)RR is important in the pathogenesis of preeclampsia., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Focal segmental glomerulosclerosis is characterized by partial (segmental) sclerotic lesions in some glomeruli (focal). Primary focal segmental glomerulosclerosis is generally considered resistant to steroid therapy. However, acromegaly is a disease that causes peculiar facial features, body types, and metabolic abnormalities due to the excessive secretion of growth hormone by a pituitary adenoma. Growth hormone has been reported to be involved in glomerular cell growth, mesangial proliferation, and glomerulosclerosis in the kidney., Case Presentation: We report a case of a Japanese patient with focal segmental glomerulosclerosis in whom decreased urinary protein was observed after surgical treatment for acromegaly., Conclusion: The patient's urinary protein improved as the concentration of growth hormone/insulin-like growth factor 1 decreased.

Aim: Changes in glucose levels during labor have not been sufficiently investigated in pregnant women. Using real-time continuous glucose monitoring, we aimed to assess glucose kinetics during labor among pregnant women with gestational diabetes mellitus (PwGDM), and those with normal glucose tolerance (PwNGT)., Methods: Japanese PwGDM and PwNGT who had planned a transvaginal delivery at Okayama University Hospital were enrolled. The correlation between changes in glucose levels during labor among the PwGDM and PwNGT groups at four time periods was assessed: (i) active phase of 1st stage of labor; (ii) 2nd stage of labor; (iii) postpartum 0-12 h; and (iv) postpartum 12-48 h., Results: In total, 18 and 22 PwGDM and PwNGT, respectively, were enrolled. During labor, both groups had similar changes in glucose levels over time, which peaked during period 3. The main effect of glucose level changes was the labor period (P < 0.001), not the presence of gestational diabetes mellitus. Furthermore, differences in glucose levels in the PwGDM group were observed between periods 1 and 2 (P = 0.037), 1 and 3 (P = 0.024), 3 and 4 (P = 0.005); differences in glucose levels in the PwNGT group were observed between periods 3 and 4 (P = 0.024)., Conclusion: During labor, both PwGDM and PwNGT groups showed similar changes in glucose levels over time. During delivery, the PwGDM who regularly measured their own glucose levels could be managed using the same nutritional management methods as those for PwNGT., (© 2019 Japan Society of Obstetrics and Gynecology.)

Background: Cotrimoxazole is the main antibiotic used in primary prophylaxis for opportunistic infections in advanced HIV infection. This drug can inhibit one of the metabolic pathways of atazanavir (ATV), such as the cytochromes P450 (CYP) 2C8/2C9 and could interfere with its safety and efficacy., Objective: We studied the drug-drug interaction (DDI) between cotrimoxazole and ATV by using therapeutic drug monitoring (TDM) and pharmacovigilance (PV) approaches., Methods: We compared a group of patients treated with cotrimoxazole and receiving an ATV-based regimen to controls. This historical cohort analysis used data from Dat'AIDS in HIV-infected patients who had at least two lowest plasma concentrations (C-trough) of ATV during their outpatient follow-up. Likewise, we used the international pharmacovigilance data from VigiBase to evaluate the notifications of hyperbilirubinemia reported with ATV., Results: In the TDM analysis, the two groups of patients (treated with cotrimoxazole and controls) were almost homogeneous concerning the main baseline features. After at least six months of ATVbased regimen, there was no significant difference in the safety threshold of the ATV C-trough [with an adjusted odds ratio (aOR) of 1.4 (95% CI: 0.5 - 4.4)] compared to controls. We observed similar results with the efficacy thresholds of ATV C-trough. Regarding the PV analysis, there was no difference in hyperbilirubinemia occurring with ATV when cotrimoxazole was concomitant, with an adjusted reporting odds ratio (aROR) of 0.9 (95% CI: 0.6 to 1.2)., Conclusion: This study showed a relevant concomitant use between Cotrimoxazole and ATV based on TDM and PV approaches., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Abnormal glucose metabolism during pregnancy is an established risk factor for preeclampsia (PE). Disruption of the balance between placental angiogenic factors is linked to PE pathophysiology. We examined whether hypoxia-induced factor-1α (HIF-1α) and protein kinase Cβ (PKCβ) are involved in the regulation of placental angiogenic factors under high-glucose conditions in vitro. The human choriocarcinoma cell lines BeWo and JEG-3, and the human trophoblast cell line HTR-8/SVneo were cultured with 10 and 25 mmol/L glucose [control glucose group (CG) and high-glucose group (HG), respectively]. We examined the changes in HIF-1α, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) expression in the CG and HG by real-time PCR and ELISA. PKC activation was also measured by ELISA. The expressions of HIF-1α, sFlt-1, PlGF, and VEGF were significantly higher in the HG than in the CG. PKC activity was significantly increased in the HG. High glucose affected the expression of angiogenic factors in choriocarcinoma cells via the PKCβ and HIF-1α pathways, suggesting their involvement in PE pathogenesis., Competing Interests: No potential conflict of interest relevant to this article was reported.

Aims/introduction: To measure longitudinal changes in resting energy expenditure and body composition of Japanese pregnant women with or without diabetes., Materials and Methods: The study population consisted of women who had delivered a live singleton neonate after 22 weeks' gestation at Okayama University Hospital from July 2013 to June 2017. Resting energy expenditure and body composition were measured in the first trimester, second trimester, third trimester and postpartum., Results: A total of 144 women participated in this study: 103 with normal glucose tolerance and 41 with diabetes. The resting energy expenditure (kcal/day) of pregnant women with normal glucose tolerance was significantly higher in the third trimester (1,644 ± 234) than in the first (1,461 ± 215) and second trimesters (1,491 ± 219), and postpartum (1,419 ± 254), whereas that of pregnant women with diabetes did not significantly change during all periods (1,568 ± 404, 1,710 ± 332, 1,716 ± 251, 1,567 ± 249). The resting energy expenditure of women with good glycemic control was lower than that of women with poor control. Fat-free mass was closely correlated with resting energy expenditure., Conclusions: The resting energy expenditure of Japanese pregnant women with normal glucose tolerance was significantly increased in the third trimester. The resting energy expenditure of women with good glycemic control was lower than that of women with poor control. Resting energy expenditure and fat-free mass are potential indexes for medical nutrition therapy in pregnant women with diabetes., (© 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

We experienced a case of advanced maternal age in which a fetus was found to be positive for trisomy 18 at re-examination following indeterminate non-invasive prenatal genetic testing (NIPT), the amniotic fluid chromosomal test revealed a normal karyotype, and confined placental mosaicism (CPM) was observed in an SNP microarray analysis of the placenta. The child was born with no defects or complications. In the present case, the result of the original NIPT at week 15 of pregnancy was indeterminate and the subsequent re-examination result was positive; since the definitive normal diagnosis was not reported until the latter half of week 21, the pregnant patient was subjected to psychological stress for a long period of time. The problem with NIPT is that most of the fetus-derived cell-free DNA in the maternal blood is not derived directly from the fetus but from the villus cells of the placenta, leading to indefinite diagnoses; for that reason, the pregnant patient was subjected to psychological stress for a long period of time. Of the 18,251 cases undergoing NIPT in the past 2 years in Japan, 51 had indeterminate results; this was the second case in which a subsequent re-examination gave a positive result for trisomy 18., Competing Interests: No potential conflict of interest relevant to this article was reported.

Although gestational hypertension (GH) is thought to be different from preeclampsia (PE), in Japan GH and PE are usually treated as the same disease (i.e., pregnancy-induced hypertension). Here we sought to determine whether there are any differences in fetal growth and maternal kidney function between pregnancies with PE and those with GH. We retrospectively analyzed 61 GH patients and 60 PE patients with singleton pregnancies who delivered at Okayama University Hospital (2008-2015). We compared maternal and perinatal outcomes and maternal kidney function parameters between the GH and PE pregnancies. The mean values of maternal age (p=0.01), gestational age at delivery (p<0.0001), placental weight (p=0.002), birth weight and height (p<0.0001, p=0.0001), and head circumference standard deviation score (p=0.007) of newborns of the GH group were significantly higher than those of the PE group. The duration until termination of PE or GH was not significantly correlated with kidney function. The birth weight percentile was significantly correlated with kidney function in PE but not GH. However, GH patients with poor kidney function and small-for-gestational age infants showed perinatal outcomes similar to those of the PE group. Monitoring kidney function is thus important for determining the severity of PE and GH., Competing Interests: No potential conflict of interest relevant to this article was reported.

Interrupted aortic arch (IAA) is fatal if not diagnosed. Prenatal diagnosis is helpful, but it is difficult to detect IAA and even more so to differentiate types A and B prenatally. Our objectives were to find a way to detect IAA using 2 views-three-vessel view (3VV) and four-chamber view (4CV)-and to differentiate between types A and B. We retrospectively analyzed fetal echocardiographic images and medical records of eight IAA patients. All eight patients had a ventricular septal defect (VSD) on 4CV. The aorta/main pulmonary artery (Ao/MPA) diameter ratio on 3VV was significantly low, which is characteristic of type B IAA. The left/right ventricular diameter (LV/RV) ratio on 4CV was 0.61± 0.17 for type A and almost 1.0 for type B. The thymus was not observed on 3VV in some type B IAA patients. These findings suggest that we could increase the number of prenatal diagnoses of IAA using the Ao/MPA ratio on 3VV and the presence of VSD on 4CV. Additionally, we could differentiate types A and B with the LV/RV ratio on 4CV, the Ao/MPA ratio, and the presence of a thymus on 3VV, which results in better management of IAA after birth.

Purpose: We continuously measured bilateral uterine artery (UA) blood flow and compared differences in UA blood flow to investigate the differences in pathophysiology between early- and late-onset pregnancy-induced hypertension (PIH) and the usefulness of continuous monitoring of UA blood flow for the prediction of early-onset PIH., Methods: The subjects were 76 PIH patients. The mean pulsatility index of bilateral UA (UAPI), an early diastolic notch in the velocity waveform, and regression curves were retrospectively examined and compared between early- and late-onset groups and the groups with and without fetal growth restriction (FGR)., Results: Regression curves of the UAPI in the early-onset group persisted at +2.0 standard deviations or more from the second to third trimester, while the UAPI in the late-onset group stayed within the normal range. A significantly higher mean UAPI with a high frequency of an early diastolic notch was observed in the early-onset group compared with the late-onset group in all pregnancy trimesters. There was a significant difference in UA resistance between the mild and severe groups and between the FGR and non-FGR groups, but to a small extent compared with the onset period., Conclusion: There was a difference in pathophysiology between early- and late-onset PIH. Continuous monitoring of UA blood flow might be useful for the prediction of early-onset PIH if high UA resistance has been observed.

Objectives: Newborns born to mothers with pregnancy-induced hypertension (PIH) are thought to be at high risk for lifestyle-related diseases, such as obesity and hypertension, in adulthood., Study Design: A longitudinal study of 78 pregnant women with PIH and their newborns, who visited Okayama University Hospital from 2009 to 2013., Main Outcome Measures: We investigated the change in growth of offspring born to mothers with PIH and compared it with the standard growth curve in Japanese to examine whether there was rapid catch-up growth during the first 3years of life., Results: Subjects were 78 pregnant women with PIH and their offspring, who visited Okayama University Hospital from 2009 to 2013. Valid responses were obtained from 29 of 78 (37.1%) women. Body weight and length at birth were at the third percentile or less in females, and at the 10th percentile or less, in males. When body weight and length were compared at 6months, 18months, and 3years old between male and female toddlers, male toddlers slowly caught up until 3years old, but female toddlers rapidly caught up in the first 6months. Furthermore, in newborns with fetal growth restriction caused by the intrauterine environment of PIH, differences in physical development between male and female toddlers were more remarkable., Conclusions: There is a significant sex difference in catch-up growth during the first 3years, which might be involved in lifestyle-related diseases in adulthood, suggesting continuous follow-up is necessary, especially for female offspring., (Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Cancer cells exhibit characteristic damage of DNA and its expression. The expression of the tumor suppressors E-cadherin and p27(Kip1) has been tested on 57 head and neck squamous cell carcinomas (HNSCC) of Indonesian subjects. HNSCC tumor samples including both primary and (unrelated) nodal cases were obtained from the archives of Indonesian hospitals, in accordance with acknowledged ethical requirements. Only modest correlation was found between reduced expression of E-cadherin or p27(Kip1) with increased malignancy of primary and nodal growth. The observed strong correlation regardless of malignancy between the expressed levels of E-cadherin and p27(Kip1) suggests that also in combination these would not help to better predict the outcome of HNSCC.

The patient was a 51-year-old woman who presented with nausea, vomiting, and abdominal pain. Detailed examination revealed a carcinoma of the descending colon with simultaneous hepatic metastasis. Because the carcinoma comprised a circumferential stenotic lesion and resection of the hepatic metastasis was feasible, combined left hemicolectomy and hepatectomy were initially performed. During postoperative adjuvant chemotherapy, the hepatic metastasis was observed to increase in size, and therefore, a second hepatectomy was performed approximately 2 years and 6 months after the initial surgery. Adjuvant chemotherapy was subsequently continued for approximately 1 year. A metastatic ovarian tumor was identified on abdominal computed tomography (CT) approximately 1 year after chemotherapy was discontinued. Bilateral salpingo-oophorectomy was performed approximately 3 years and 6 months after the initial surgery. Histopathological examination revealed the lesion to be a colon carcinoma metastasis.

There is no standard approach for second-line chemotherapy after a failure of the first-line regimen, fluorouracil and cisplatin -based chemotherapy in patients with unresectable or recurrent esophageal cancer. We have treated with biweekly nedaplatin (CDGP 40 mg/m²) in combination with docetaxe (l DOC 30 mg/m²) as second-line chemotherapy and investigated its efficacy and safety. Fifteen patients were retrospectively assessed in this study. Response rate (RR) and disease control rate (DCR) were 0 and 6.7%, respectively. Median time to progression( TTP) and median survival time( MST) were 2.1 and 7.0 months. Neutropenia and thrombocytopenia of grade 3 were seen in 4 (26.7%) and 1 (6.7%) patients, but no other serious adverse effects were detected. Based on the results, a biweekly nedaplatin/docetaxel regimen was safely received on an outpatient basis but not enough to provide a significant survival benefit. Quality of life and minimization of adverse effects are key considerations in second-line chemotherapy. Thereby, future trials should assess a quality of life in conjunction with different combination of active drugs and doses.

A 70-year-old man was found to have advanced gastric cancer with a deep ulcer and multiple lymph-node metastases. Although the tumor was resectable, we predicted that the patient would have a poor outcome. We therefore administered neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 to improve the prognosis before curative resection. On day 15 of chemotherapy, sudden abdominal pain occurred, and we performed an emergency surgery for a diagnosis of panperitonitis due to gastric cancer perforation. The defect in the gastric wall was about 2 cm in diameter and was located in the anterior wall of the antrum, consistent with the center of the tumor. The operative findings suggested that the perforation was caused by chemotherapy-induced necrosis of gastric cancer cells. We saved the patient's life, but intensive care with high-dose catecholamine therapy was needed for several days after the surgery. Gastric cancer perforation induced by neoadjuvant chemotherapy appeared to be more severe than perforation caused by other factors. The adverse effects of chemotherapy apparently increased the severity. Our findings suggest that the risk of gastric cancer perforation should be borne in mind when we administer neoadjuvant chemotherapy to patients who have advanced gastric cancer with a deep ulcer.

Because gastric submucosal tumors can be treated by local resection without lymph-node dissection, laparoscopic local resection is widely used to manage relatively small tumors less than 5 cm in diameter. On the other hand, single-incision laparoscopic surgery (SILS) to perform laparoscopic cholecystectomy was feasible. SILS requires only a single incision in the umbilical region; it has better cosmetic outcomes than conventional laparoscopic surgery. The relative difficulty and ease of local gastric resection depends to a large part on tumor location and morphologic characteristics. Extraluminal submucosal tumor of the stomach can be locally resected by SILS using an automated suturing device regardless of tumor location. Intraluminal tumor located in the greater curvature of the gastric body can be treated by SILS, whereas intraluminal lesions located in the lesser curvature and near the gastric cardia or pylorus are difficult to manage by SILS. Laparoscopic and endoscopic cooperative surgery (LECS) is useful for resecting an appropriate amount of tissue at any site. In patients with lesions located near the gastric cardia or pylorus, closure with an automatic suture device may be difficult. Such patients should be switched to reduced-port surgery with a coaxial port, and hand-sewn closure is useful.