Changing the standardised obstetric care by expanded carrier screening and counselling: a multicentre prospective cohort study.

BACKGROUND: Expanded genetic screening before conception or during prenatal care can provide a more comprehensive evaluation of heritable fetal diseases. This study aimed to provide a large cohort to evaluate the significance of expanded carrier screening and to consolidate the role of expanded genetic screening in prenatal care. METHODS: This multicentre, retrospective cohort study was conducted between 31 December 2019 and 21 July 2022. A screening panel containing 302 genes and next-generation sequencing were used for the evaluation. The patients were referred from obstetric clinics, infertility centres and medical centres. Genetic counsellors conducted consultation for at least 15 min before and after screening. RESULTS: A total of 1587 patients were screened, and 653 pairs were identified. Among the couples who underwent the screening, 62 (9.49%) had pathogenic variants detected on the same genes. In total, 212 pathogenic genes were identified in this study. A total of 1173 participants carried at least one mutated gene, with a positive screening rate of 73.91%. Among the pathogenic variants that were screened, the gene encoding gap junction beta-2 (GJB2) exhibited the highest prevalence, amounting to 19.85%. CONCLUSION: Next-generation sequencing carrier screening provided additional information that may alter prenatal obstetric care by 9.49%. Pan-ethnic genetic screening and counselling should be suggested for couples of fertile age.

Tenofovir alafenamide or tenofovir disoproxil fumarate in pregnancy to prevent HBV transmission: Maternal ALT trajectory and infant outcomes.

BACKGROUND: The use of antiviral agents, specifically tenofovir disoproxil fumarate (TDF), in pregnant women to prevent mother-to-child HBV transmission is a key step towards hepatitis elimination. However, data on using tenofovir alafenamide (TAF) is insufficient. The frequent occurrence of postpartum ALT flares may impact the clinical implementation. METHODS: The maternal and infant outcomes were compared in multi-centre trials of high viral load HBsAg/HBeAg+ pregnant women receiving TAF or TDF from the third trimester until 2 weeks postpartum with intensive follow-ups. To explore the dynamic pre- and postpartum changes in ALT levels, we used a group-based trajectory model for analysing data of 332 women from three prospective studies. RESULTS: After treatment, the maternal HBV DNA levels significantly decreased from baseline to delivery: 7.87 ± 0.59 to 3.99 ± 1.07 Log10 IU/mL TAF (n = 78) and 8.30 ± 0.36 to 4.47 ± 0.86 Log10 IU/mL (TDF, n = 53), with viral load reductions of 3.87 versus 3.83 Log10 IU/mL. The HBsAg-positive rates among 12-month-old infants were 1.28% (1/78) versus 1.82% (1/55) respectively (p = 1.00). Of the TAF or TDF-treated mothers, 25.64% versus 16.98% experienced ALT > 2X ULN, and 11.54% versus 1.89% received extended antiviral treatment. Our model revealed four distinct ALT patterns: stable ALT (87.2%), moderate (8.0%) or marked (2.4%) postpartum flares, or prepartum elevations (2.4%). CONCLUSIONS: TAF effectively reduces mother-to-child HBV transmission, but prophylaxis failure still occurred in few cases. Postpartum ALT flares are common in women receiving TAF or TDF during pregnancy. Approximately 12.8% of mothers may require extended postpartum antiviral treatment. CLINICAL TRIAL NUMBER: NCT03695029 (ClinicalTrials.gov).

Risk of placenta accreta spectrum following myomectomy: a nationwide cohort study.

BACKGROUND: Whether myomectomy increases the risk of placenta accreta spectrum in the following pregnancies remains controversial. OBJECTIVE: This study aimed to investigate the effect of myomectomy on the risk of placenta accreta spectrum in the following pregnancies. Moreover, different methods of myomectomy on the risk of placenta accreta spectrum were explored. STUDY DESIGN: A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database, including all pregnant patients in Taiwan who gave birth between January 2008 and December 2017. A 1:1 propensity score estimation matching was performed for the analysis of myomectomy on the risk of placenta accreta spectrum. Among pregnant patients who received myomectomy, different methods of myomectomy on the risk of placenta accreta spectrum were compared with the control group. RESULTS: Among the 1,371,458 pregnant patients in this study, 11,255 pregnant patients had a history of myomectomy. The risk of placenta accreta spectrum was higher in pregnant patients with a history of myomectomy than in pregnant patients without a history of myomectomy (incidence: 0.96% vs 0.20%; adjusted odds ratio, 2.28; 95% confidence interval, 1.85-2.81; P<.01). Among pregnant patients with a history of myomectomy, 5045 (46.87%) received laparotomic myomectomy, 3973 (36.93%) received laparoscopic myomectomy, and 1742 (16.20%) received hysteroscopic myomectomy. The incidence of placenta accreta spectrum was higher in the hysteroscopic group than in the laparotomic group or the laparoscopic group (1.89% [hysteroscopic group] vs 0.71% [laparotomic group] and 0.81% [laparoscopic group]; P<.05). Compared with patients without a history of myomectomy, the adjusted odds ratio for placenta accreta spectrum was 3.88 (95% confidence interval, 2.68-5.63; P<.05) in the hysteroscopic group. CONCLUSION: Myomectomy, especially hysteroscopic myomectomy, is associated with an increased risk of placenta accreta spectrum in the subsequent pregnancy.

Surgical resection for congenital lung malformation: Lessons learned from thoracotomy to biportal thoracoscopy under one-lung ventilation.

BACKGROUND: The purpose of this study is to compare the clinical characteristics and surgical outcomes of thoracotomy and video-assisted thoracoscopic surgery (VATS) in children with congenital lung malformations (CLMs) in a tertiary referring center and to report our modified biportal VATS setting. METHODS: This is a single-center retrospective chart review study including children who underwent surgical resection for CLMs between January 2007 and December 2020. Patient characteristics and surgical outcomes were compared between open and thoracoscopy, as well as conventional VATS and biportal VATS. Biportal setting included an anterior utility wound and a camera trocar wound with one-lung ventilation. RESULTS: A total of 100 patients were identified. Twenty patients received thoracotomy, and 80 patients received VATS (67 conventional and 13 biportal VATS). The median age at operation was 0.4 months in the thoracotomy group and 4.7 months in the VATS group. More patients in the thoracotomy group had preoperative symptoms, comorbidities, and emergent operations. The patients who underwent thoracotomy had significantly longer postoperative ICU stays, chest tube durations, hospital stays, and more complications. The pathological analysis revealed 67 congenital pulmonary airway malformations, 27 pulmonary sequestration, 6 hybrid lesions, and one accompanying pleuropulmonary blastoma. Compared to conventional VATS, the ICU stay was shorter in the biportal VATS group, with comparable operative durations, hospital stay and complications. CONCLUSION: VATS for CLMs is associated with better postoperative recovery and fewer complications. Biportal VATS is also a safe and feasible approach.

The "rail sign": an ultrasound finding in placenta accreta spectrum indicating deep villous invasion and adverse outcomes.

BACKGROUND: Ultrasound has demonstrated a high accuracy in the prenatal diagnosis of placenta accreta spectrum. However, it is not known whether ultrasound findings can pinpoint the depths of villous invasion, recommend surgical strategies, and predict clinical outcomes. OBJECTIVE: We described an ultrasound descriptor for the placenta accreta spectrum and investigated whether it can predict the severity of villous invasion and clinical outcomes. STUDY DESIGN: The patients with placenta accreta spectrum in this retrospective cross-sectional study were diagnosed and managed in our hospital from 2002 to 2017. The placenta, with overlying myometrium and bladder, was mapped with color Doppler sonography while the patient's bladder was full. A "rail sign" was defined as 2 parallel neovascularizations depicted by color Doppler sonography over the uterovesical junction and bladder mucosa, with interconnecting bridging vessels perpendicular to both. The patients received serial ultrasound examinations and surgery at our hospital. An unpaired t test and Pearson chi-square test compared the pathology subtypes, surgical strategies, and clinical outcomes in patients with or without a rail sign. RESULTS: We enrolled 133 consecutive cases of placenta accreta spectrum confirmed either by surgical inspection or pathology examination. Patients with a rail sign had a significantly higher risk of an abnormally invasive placenta (placenta increta or placenta percreta) than those patients without a rail sign (83.3% [60 of 72] vs 27.9% [17 of 61]; odds ratio, 12.94; P<.001). In addition, patients with a rail sign had a higher probability of perioperative approaches, including preoperative vascular control (58.3% [42 of 72] vs 21.3% [13 of 61]; odds ratio, 5.17; P<.001) and uterine artery embolization (34.7% [25 of 72] vs 11.5% [7 of 61]; odds ratio, 4.1; P=.0002]. Furthermore, patients with a rail sign carried a higher risk of adverse clinical outcomes than patients without a rail sign, such as blood transfusion (80.6% [58 of 72] vs 36.1% [22 of 61]; odds ratio, 7.34; P<.001], admission to the intensive care unit (33.3% [24 of 72] vs 16.4% [10 of 61]; odds ratio, 2.55; P=.026), hysterectomy (75% [54 of 72] vs 24.6% [15 of 61]; odds ratio, 9.2; P<.001), and bladder invasion (16.7% [12 of 72] vs 4.9% [3 of 61]; odds ratio, 3.86; P=.033). Notably, the negative predictive value of bladder invasion was 95.1%, indicating a high confidence to reject bladder invasion while the rail sign was negative. When the rail sign was used as a screening test, the positive likelihood ratio of predicting deep villous invasion was 3.64 and correlated with an increased probability of 20% to 25%. Patients with a rail sign also had a greater blood loss (2944±2748 mL vs 1530±1895 mL; P<.001) and a longer hospital stay (11.9±10.9 days vs 8.6±7.1 days; P=.036) than patients without a rail sign. CONCLUSION: A "rail sign" depicted by color Doppler sonography correlates with deeper villous invasion, additional perioperative approaches, and more adverse outcomes.

Unveiling the role of microRNA-7 in linking TGF-ß-Smad-mediated epithelial-mesenchymal transition with negative regulation of trophoblast invasion.

Several pregnancy complications result from abnormal trophoblast invasion. The dichotomous effect of TGF-ß on epithelial-mesenchymal transition (EMT) between trophoblast invasion and cancer progression remains unknown and a critical concern. We attenuated the expression of TGF-ß type 1 receptor (coding by TGFBR1) with RNA interference in trophoblastic cells and significantly enhanced the trophoblastic invasion. Analysis of microRNA profiles in trophoblasts indicated microRNA-7 as a key molecule linking TGF-ß with the negative regulation of trophoblast invasion. We then attenuated TGFBR1 and miR-7 transcription by transducing either short hairpin RNA targeting TGFBR1 or anti-miR-7-locked nucleonic acid, and we observed an up-regulation of EMT-related transcription factors (TFs) and their downstream effectors, causing a mesenchymal transition of trophoblasts. Conversely, overexpression of TGFBR1 or miR-7 led to the epithelial transition of trophoblasts. Our results showed that TGF-ß-induced miR-7 expression negatively modulated the TGF-ß-SMAD family member 2-mediated EMT pathway via targeting EMT-related TFs and down-regulating their mesenchymal markers. These findings possibly explain, at least in part, why TGF-ß exerts an opposite effect on EMT during trophoblast invasion and cancer progression.-Shih, J.-C., Lin, H.-H., Hsiao, A.-C., Su, Y.-T., Tsai, S., Chien, C.-L., Kung, H.-N. Unveiling the role of microRNA-7 in linking TGF-ß-Smad-mediated epithelial-mesenchymal transition with negative regulation of trophoblast invasion.

Mosaic paternal haploidy in a patient with pancreatoblastoma and Beckwith-Wiedemann spectrum.

Pancreatoblastoma is a rare type of pancreatic cancer in children. Here, we describe a case in which Beckwith-Wiedemann syndrome (BWS) was first suspected because of placental mesenchymal dysplasia. Although the baby did not show the stigmata characteristic of BWS or abnormal peripheral blood methylation, she developed a massive pancreatoblastoma 2 months later. She survived after partial excision of the tumor and chemotherapy. The methylation pattern of the pancreatoblastoma tissue was typical of BWS. Single nucleotide polymorphism (SNP) array analyzes revealed that the pancreatoblastoma tissue had genome-wide loss of maternal alleles. Peripheral blood and nontumor pancreatic tissue showed normal biparental genomic contribution. Interphase fluorescence in situ hybridization analysis with centromeric probes for chromosomes 2 and 11 revealed haploid pancreatoblastoma cells, whereas the placental mesenchymal dysplasia tissue and nontumor pancreas tissue showed diploidy. SNP genotype analysis suggested the presence of mosaicism with the pancreatoblastoma tissue having a different paternal haplotype than that of the peripheral blood and nontumor pancreatic tissue. We report for the first time mosaic paternal haploidy associated with pancreatoblastoma. Babies with placental mesenchymal dysplasia, even those without a definitive diagnosis of BWS, need to be closely followed for the occurrence of embryonic tumors.

Extracorporeal membrane oxygenation application in post-partum hemorrhage patients: Is post-partum hemorrhage contraindicated?

Extracorporeal membrane oxygenation (ECMO) is commonly used in patients who experience circulatory arrest or significant cardiac dysfunction and is associated with improved clinical outcomes. We conducted a retrospective observational study on ECMO application at a single tertiary center over a five-year period. Five patients who suffered post-partum hemorrhage resulting from uterine atony were treated with ECMO. The mean age was 36.8 ± 3.9 years; the mean gestational age was 37.8 ± 2.2 weeks; the initial mean maternal hemoglobin level was 5.0 ± 2.4 mg/dL; and the mean estimated blood loss was 3260 ± 1545 mL before treatment. All patients were treated with venoarterial ECMO and one was treated with both venoarterial and venovenous ECMO. The mean ECMO usage duration was 32.6 ± 18.8 h (range 10-54). Four (80%) patients survived until discharge without experiencing neurological sequela. ECMO should not be a contraindication for treatment of post-partum hemorrhage and such patients should be weaned as soon as possible to ensure the early recovery of cardiac function.

Amniotic membrane and adipose-derived stem cell co-culture system enhances bone regeneration in a rat periodontal defect model.

BACKGROUND/PURPOSE: Periodontal disease is a chronic inflammatory process that potentially leads to alveolar bone destruction and tooth loss. Tissue engineering combined with stem cell therapy is a potential effective treatment for periodontal bone loss. Amniotic membrane (AM) is a potential scaffold enriched with multiple growth factors. It has the effects of anti-inflammation, antiangiogenesis, and immunosuppression. Herein, we used adipose-derived stem cells (ADSCs) and an AM co-cultured system to study bone regeneration in a rat periodontal defect model in vivo. METHODS: Human ADSCs were isolated from the infrapatellar fat pad, and characterized by flow cytometry, reverse transcription-polymerase chain reaction, and multipotent differentiation assays. The co-culture system was applied in the periodontal two-wall osseous defect in a rat model, and computed tomography was used to measure the effect. RESULTS: Human ADSCs isolated from the infrapatellar fat pad showed spindle-like morphology. Flow cytometry results demonstrated that ADSCs expressed a high level of CD90 and CD105, but not CD31, CD34, and CD45. ADSCs strongly expressed stemness genes, including SOX2, OCT4, NANOG, and KLF4 on different passages. Furthermore, ADSCs were able to differentiate into osteogenic, chondrogenic, and adipogenic cells. In the periodontal osseous defect rat model, ADSCs and the AM co-culture system significantly increased bone regeneration. CONCLUSION: This study provides the basis for using ADSCs with an AM co-culture system as stem cell therapy and scaffold transplantation in clinical periodontology.

Comparison of 3 Risk Estimation Methods for Predicting Cardiac Outcomes in Pregnant Women With Congenital Heart Disease.

BACKGROUND: Three risk estimation methods for predicting the cardiac outcomes of pregnancy in women with heart disease have been proposed. This study was designed to compare their prediction performance in an Asian cohort with congenital heart disease (CHD). METHODS AND RESULTS: This study enrolled pregnant women with CHD who delivered their babies after the 20th gestational week between 1985 and 2011. Of 268 pregnancies in 190 women with CHD, 18 (6.7%) had cardiac complications. The incidence of maternal cardiac events among women with a CARPREG index of 0, 1 or 2 was 3.4%, 27.3% and 100%. The incidence was 2.7%, 8.6%, 11.1%, 40% and 17.6% for those with a ZAHARA score 0-0.5, 0.51-1.5, 1.51-2.5, 2.51-3.5 and >3.5. Among patients with a modified World Health Organization (WHO) classification I, II, III and IV, the incidence of maternal cardiac events was 0%, 4.0%, 12.2% and 25.7%. The c-statistic was 0.732 (95% confidence interval (CI): 0.589, 0.876; P<0.001) for the CARPREG score, 0.737 (95% CI: 0.611, 0.864; P=0.001) for the ZAHARA score and 0.827 (95% CI: 0.745, 0.909; P<0.001) for the WHO classification. CONCLUSIONS: All 3 risk estimation methods had good performance in predicting maternal cardiac outcomes; however, the modified WHO classification demonstrated superior discrimination and calibration.

Light-guided hysteroscopic resection of complete septate uterus with preservation of duplicated cervix.

The objective of the present study, performed at a tertiary university hospital, was to propose a novel method of hysteroscopic resection of complete septate uterus with preservation of duplicated cervix. The retrospective study included 5 women with complete septate uterus and cervical duplication and who also experienced infertility with or without pregnancy loss. All patients underwent bougie-guided or light-guided hysteroscopic perforation of the uterine septum above the endocervix, followed by septum resection. The success rate of complete uterine septum perforation under bougie guidance was 60% (3 of 5 procedures), and of light guidance was 100% (2 procedures). After hysteroscopic septum resection, 2 of 5 women achieved pregnancy within 3 months and delivered uneventfully at term. It is concluded that light guidance is superior to bougie guidance for hysteroscopic perforation of complete septate uterus with preservation of the duplicated cervix.

Long-term survival and renal outcomes of thrombotic microangiopathy in pregnancy: A retrospective cohort study.

OBJECTIVE: Thrombotic microangiopathy (TMA) in pregnancy can rapidly progress, leading to severe morbidities. This study aimed to compare baseline demographics and clinical outcomes between pregnant women with and without TMA. METHODS: Using the National Health Insurance Research Database, 207 patients with pregnancy-related TMA from January 1, 2006 to December 31, 2015 were enrolled. Their data were compared with a 1:4 propensity score-matched cohort of 828 pregnant women without TMA to evaluate mortality and end-stage renal disease (ESRD) risks. Cox proportional hazards models were used to estimate the adjusted hazard ratio and 95% confidence intervals. RESULTS: A total of 1035 participants were included. The risks of mortality and ESRD were 4.46 and 5.97 times higher for the TMA cohort, respectively. Subgroup analysis revealed higher mortality and ESRD risks in patients with TMA aged >40 years with a history of hypertension, stroke, cancer, concomitant stroke, malignant hypertension, or gastroenterocolitis than in the matched cohort. CONCLUSION: Pregnant patients with TMA, especially those older and with comorbidities and organ involvement, faced increased mortality and ESRD risks. Physicians should collaborate with obstetricians throughout the prenatal and postpartum periods for these patients.

Serostatus of echovirus 11, coxsackievirus B3 and enterovirus D68 in cord blood: The implication of severe newborn enterovirus infection.

BACKGROUND: Maternal transplacental antibody is an important origins of passive immunity against neonatal enterovirus infection. Echovirus 11 (E11) and coxsackievirus B3 (CVB3) are important types causing neonatal infections. There were few investigations of enterovirus D68 (EVD68) infection in neonates. We aimed to investigate the serostatus of cord blood for these three enteroviruses and evaluate the factors associated with seropositivity. METHODS: We enrolled 222 parturient (gestational age 34-42 weeks) women aged 20-46 years old between January and October 2021. All participants underwent questionnaire investigation and we collected the cord blood to measure the neutralization antibodies against E11, CVB3 and EVD68. RESULTS: The cord blood seropositive rates were 18% (41/222), 60% (134/232) and 95% (211/222) for E11, CVB3 and EVD68, respectively (p < 0.001). Geometric mean titers were 3.3 (95% CI 2.9-3.8) for E11, 15.9 (95% CI 12.5-20.3) for CVB3 and 109.9 (95% CI 92.4-131.6) for EVD68. Younger parturient age (33.8 ± 3.6 versus 35.2 ± 4.4, p = 0.04) was related to E11 seropositivity. Neonatal sex, gestational age and birth body weight were not significantly different between the seropositive group and the seronegative group. CONCLUSION: Cord blood seropositive rate and geometric mean titer of E11 were very low, so a large proportion of newborns are susceptible to E11. The circulation of E11 was low after 2019 in Taiwan. A large cohort of immune naïve newborns existed currently due to lack of protective maternal antibodies. It is imminent to monitor the epidemiology of neonates with enterovirus infections and strengthen the relevant preventive policies.

Prediction of clinical outcomes in women with placenta accreta spectrum using machine learning models: an international multicenter study.

INTRODUCTION: Placenta accreta spectrum is a major obstetric disorder that is associated with significant morbidity and mortality. The objective of this study is to establish a prediction model of clinical outcomes in these women. MATERIALS AND METHODS: PAS-ID is an international multicenter study that comprises 11 centers from 9 countries. Women who were diagnosed with PAS and were managed in the recruiting centers between 1 January 2010 and 31 December 2019 were included. Data were reanalyzed using machine learning (ML) models, and 2 models were created to predict outcomes using antepartum and perioperative features. ML model was conducted using python® programing language. The primary outcome was massive PAS-associated perioperative blood loss (intraoperative blood loss ≥2500 ml, triggering massive transfusion protocol, or complicated by disseminated intravascular coagulopathy). Other outcomes include prolonged hospitalization >7 days and admission to the intensive care unit (ICU). RESULTS: 727 women with PAS were included. The area under curve (AUC) for ML antepartum prediction model was 0.84, 0.81, and 0.82 for massive blood loss, prolonged hospitalization, and admission to ICU, respectively. Significant contributors to this model were parity, placental site, method of diagnosis, and antepartum hemoglobin. Combining baseline and perioperative variables, the ML model performed at 0.86, 0.90, and 0.86 for study outcomes, respectively. Ethnicity, pelvic invasion, and uterine incision were the most predictive factors in this model. DISCUSSION: ML models can be used to calculate the individualized risk of morbidity in women with PAS. Model-based risk assessment facilitates a priori delineation of management.

Prediction of success of uterus-preserving management in women with placenta accreta spectrum (CON-PAS score): A multicenter international study.

OBJECTIVE: To create a model for prediction of success of uterine-preserving procedures in women with placenta accreta spectrum (PAS). METHODS: PAS-ID is a multicenter study that included 11 centers from 9 countries. Women with PAS, who were managed between January 1, 2010 and December 31, 2019, were retrospectively included. Data were split into model development and validation cohorts, and a prediction model was created using logistic regression. Main outcome was success of uterine preservation. RESULTS: Out of 797 women with PAS, 587 were eligible. Uterus-preserving procedures were successful in 469 patients (79.9%). Number of previous cesarean sections (CS) was inversely associated with management success (adjusted odds ratio [aOR] 0.02, 95% confidence interval [CI] 0.001-3.63 with five previous CS). Other variables were complete placental invasion (aOR 0.14, 95% CI 0.05-0.43), type of CS incision (aOR 0.04, 95% CI 0.01-0.25 for classical incision), compression sutures (aOR 2.48, 95% CI 1.00-6.16), accreta type (aOR 3.76, 95% CI 1.13-12.53), incising away from placenta (aOR 5.09, 95% CI 1.52-16.97), and uterine resection (aOR 102.57, 95% CI 3.97-2652.74). CONCLUSION: The present study provides a prediction model for success of uterine preservation, which may assist preoperative and intraoperative decisions, and promote incorporation of uterine preservation procedures in comprehensive PAS protocols.

Late outgrowth endothelial cells derived from Wharton jelly in human umbilical cord reduce neointimal formation after vascular injury: involvement of pigment epithelium-derived factor.

OBJECTIVE: The number of endothelial progenitor cells (EPCs) that can be obtained from adult bone marrow and peripheral blood to treat cardiovascular diseases is limited. The goal was to examine the endothelial potential of Wharton jelly in human umbilical cord (WJC)-derived stem cells and evaluate their potential to affect neointimal formation after vascular injury. METHODS AND RESULTS: Mesenchymal cells (MCs) were isolated from WJC and cultured in endothelial growth medium. Differentiation into late outgrowth endothelial cells (WJC-OECs) was demonstrated by incorporation of acetylated low-density lipoprotein and expression of the endothelial-specific markers. Transplantation of these cells into wire-injured femoral arteries in mice led to rapid reendothelialization. At 4 weeks after injury, the neointima/media area ratio was reduced and strong expression of pigment epithelium-derived factor (PEDF) compared to saline-or MC- or cord blood-OEC-treated mice. WJC-OECs-conditioned medium has an extremely strong capacity to inhibit the migration and proliferation of smooth muscle cells. The effects were inhibited by neutralizing antibody for PEDF and by siRNA silencing of PEDF. CONCLUSIONS: We firstly demonstrated the presence of a cell population within WJC that has the potential to differentiate into OECs. Transplantation of WJC-OECs may play a crucial role in reestablishing endothelial integrity in injured vessels, thereby inhibiting neointimal hyperplasia. These findings have implications for a novel and practical cell-based therapy for vascular diseases.

Comparison of vascularization and overall perfusion of the bladder wall between women with and without overactive bladder syndrome.

The pathophysiology of female overactive bleeder syndrome (OAB) remains undetermined. Our aim is to elucidate the role of vacularization and overall perfusion of the bladder wall in women with OAB. Between 2010 and 2016, women with OAB and the asymptomatic controls were enrolled. Women with OAB were treated with tolterodine. Women with OAB (n = 40) had higher vascularization index (0.40 ± 0.57 versus 0.17 ± 0.22, p = 0.003), vascularization-flow index (0.15 ± 0.28 versus 0.05 ± 0.08, p = 0.003) and thicker trigone (0.56 ± 0.13 cm versus 0.47 ± 0.11 cm, p = 0.004), compared with the controls (n = 34). The following optimum cut-off values to predict OAB were determined: (1) vascularization index (%) ≥ 0.16, (2) vascularization-flow index ≥ 0.032, and (3) trigone bladder wall thickness ≥ 0.47 cm with an area under the curve of 0.71, 0.71 and 0.70, respectively. Correlation analysis showed that a significant correlation between urgency and vascularization index/vascularization-flow index (Spearman's rho = 0.34 and 0.35, respectively, all p < 0.01). However, after 12 weeks of tolterodine treatment, the vascularization index, flow index and vascularization-flow index did not differ between baseline and after treatment. In conclusion, women with OAB have higher vascularization and overall perfusion of the bladder wall, compared women without OAB. However, vascularization and overall perfusion did not change after antimuscarinic treatment.

Sonographic diagnosis of fetal malformations associated with mycophenolate mofetil exposure in utero.

Mycophenolate mofetil has been shown to have teratogenic properties in animal studies and clinical reports. We report a case of major fetal malformation likely caused by mycophenolate mofetil exposure in utero in a 36 year old patient with systemic lupus erythematosus. The diagnosis was made by ultrasonography at 22 weeks of gestation.