Ad5-nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants.

Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.

Comparison of performance between O-RADS, IOTA simple rules risk assessment and ADNEX model in the discrimination of ovarian Brenner tumors.

PURPOSE: To describe the clinical and sonographic features of ovarian benign Brenner tumor (BBT) and malignant Brenner tumor (MBT), and to compare performance of four diagnostic models in differentiating them. METHODS: Fifteen patients with BBTs and nine patients with MBTs were retrospectively identified in our institution from January 2003 and December 2021. One ultrasound examiner categorized each mass according to ovarian-adnexal reporting and data system (O-RADS), international ovarian tumor analysis (IOTA) Simple Rules Risk (SR-Risk) assessment and assessment of different neoplasias in the adnexa (ADNEX) models with/without CA125. Receiver operating characteristic curves were generated to compare diagnostic performance. RESULTS: Patients with MBT had higher CA125 serum level (62.5% vs. 6.7%, P = 0.009) and larger maximum diameter of lesion (89 mm vs. 43 mm, P = 0.009) than did those with BBT. BBT tended to have higher prevalence of calcifications (100% vs. 55.6%, P = 0.012) and acoustic shadowing (93.3% vs. 33.3%, P = 0.004), and lower color scores manifesting none or minimal flow (100.0% vs. 22.2%, P < 0.001). Areas under curves of O-RADS, IOTA SR-Risk and ADNEX models with/without CA125 were 0.896, 0.913, 0.892 and 0.896, respectively. There were no significant differences between them. CONCLUSION: BBTs are often small solid tumors with sparse color Doppler signals, which contain calcifications with posterior acoustic shadowing. The most common pattern of MBT is a large multilocular-solid or solid mass with irregular tumor borders, and most were moderately or richly vascularized at color Doppler. These four models have excellent performance in distinguishing them.

[Clinical and genetic analysis of a fetus with 17q12 microdeletion syndrome].

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a fetus with 17q12 microdeletion syndrome. METHODS: A fetus with 17q12 microdeletion syndrome who was diagnosed at Huzhou Maternal & Child Health Care Hospital in June 2020 was selected as the study subject. Clinical data of the fetus was collected. The fetus was subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). To determine the origin of fetal chromosomal abnormality, its parents were also subjected to CMA assay. The postnatal phenotype of the fetus was also investigated. RESULTS: Prenatal ultrasound revealed polyhydramnios and fetal renal dysplasia. The fetus was found to have a normal chromosomal karyotype. CMA has detected a 1.9 Mb deletion in the 17q12 region, which has encompassed five OMIM genes including HNF1B, ACACA, ZNHIT3, CCL3L1 and PIGW. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 17q12 microdeletion was predicted as pathogenic copy number variation (CNV). CMA analysis has detected no pathogenic CNV in both parents. After birth, the child was found to have renal cysts and abnormal brain structure. Combined with the prenatal findings, the child was diagnosed with 17q12 microdeletion syndrome. CONCLUSION: The fetus has 17q12 microdeletion syndrome presenting as abnormalities of the kidney and central nervous system, which are strongly correlated with functional defects of the deletion region involving the HNF1B and other pathogenic genes.

Ultrasound in the prediction of birthweight discordance in dichorionic twins.

INTRODUCTION: Large birthweight discrepancy has been identified as a risk factor for perinatal morbidity and mortality in twin pregnancies. However, it remains unclear whether such discordance can be predicted by various biological indices with specific cut-off values, and how these depend on the gestational age. We aimed to determine the most effective way to predict large birthweight discordance at various gestational ages. MATERIAL AND METHODS: A retrospective cohort study of dichorionic twins, live-born between 2008 and 2018, was conducted. Discordances in biparietal diameter, head circumference, humerus and femur length, abdominal circumference, and estimated fetal weight were calculated-([larger twin - smaller twin] / larger twin) × 100%-and compared between those with and without a large birthweight discordance (≥20%). Receiver operating characteristic curves were constructed to analyze the predictive characteristics of each parameter. RESULTS: Of 598 dichorionic twin pregnancies included, 83 (13.9%) had a birthweight discordance ≥20%. Group differences in biparietal diameter and head circumference discordance were the earliest to emerge (before 20 weeks of gestation), but became insignificant after 36 weeks, followed by humerus and femur length, estimated fetal weight discordance (after 20 weeks), and abdominal circumference discordance (after 28 weeks). The best predictors (with cut-off values) were discordance in biparietal diameter ≥7.8% at <20 weeks, head circumference ≥4.5% at 20-23+6  weeks, humerus length ≥4.5% at 24-27+6  weeks, and estimated fetal weight discordance (≥11.6% at 28-31+6  weeks, ≥10.5% at 32-35+6  weeks, and ≥15.0% ≥36 weeks), with sensitivity and specificity of 52%-77% and 69%-82%, respectively. CONCLUSIONS: Different predictors and cut-off values may be useful for predicting large inter-twin birthweight discordance in dichorionic twins at different gestational ages. It is more accurate to use biparietal diameter and head circumference discordance in the early second trimester, humerus length discordance in the late second trimester, and estimated fetal weight discordance in the third trimester.

Evaluation of the clinical diagnostic value of traditional inflammatory markers and novel biomarkers in intracellular bacterial bloodstream infections.

OBJECTIVES: The clinical symptoms of the patients with intracellular bacterial bloodstream infections (Intra-bac BSIs) are atypical, and no early and accurate diagnostic biomarkers exist, which can easily lead to misdiagnosis, inappropriate and delayed treatment. Therefore, it is imperative to find novel biomarkers to help clinical diagnosis of Intra-bac BSIs. The present study was initiated to evaluate the diagnostic values of traditional inflammatory biomarkers (PCT, WBC and NEU% in identifying the patients with Intra-bac BSIs, and to further explore into the possibility of using suPAR and sCD14-ST as novel biomarkers for Intra-bac BSIs. METHODS: A multi-center retrospective study was conducted in three teaching hospitals in Chongqing. A total of 146 cases with BSIs, including 73 cases with Intra-bac BSIs and 73 cases with extracellular bacterial BSIs (Extra-bac BSIs) were enrolled in the retrospective study. We then prospectively enrolled 34 patients with Intra-bac BSIs, 34 patients with Extra-bac BSIs, 34 patients with viral infection and with normal medical examination results as a control group for further detection of sCD14-ST and suPAR by ELISA. RESULTS: PCT levels, WBC counts and NEU% in patients with Intra-bac BSIs were not increased or minimally increased, they were significantly lower than that with Extra-bac BSIs (P < 0.05), especially those with the Brucella bacterial BSIs, demonstrated a respective negative rate of 84% and 92% for PCT and WBC counts. In the prospective study, the levels of suPAR and sCD14-ST in both the Intra-bac BSIs and the Extra-bac BSIs groups were significantly higher than those in the viral infection group and normal control group (P < 0.05). The areas under the curve (AUC) of Intra-bac BSIs were 0.830 for suPAR, and 0.855 for sCD14-ST. The sensitivity, specificity, Youden's index for suPAR and sCD14-ST were respectively 76.5%, 88.2%, 0.647 and 94.1%, 64.7%, 0.588. CONCLUSIONS: Our multi-center study demonstrated that while the traditional inflammatory markers such as PCT, WBC counts, NEU% could not be served as promising diagnostic markers for Intra-bac BSIs; CRP can help guide the diagnosis of Intra-bac BSIs; Both suPAR and sCD14-ST could be considered as novel diagnostic biomarkers for Intra-bac BSIs as they showed good diagnostic accuracies in Intra-bac BSIs, especially suPAR.

Prediction of cesarean hysterectomy in placenta previa complicated with prior cesarean: a retrospective study.

BACKGROUND: The prevalence of both placenta previa and cesarean are on the rise. Multiple adverse outcomes are critically increased when placenta previa is subsequent to prior cesarean. The purpose of the present study is to develop a pre-surgical method for predicting adverse outcomes in pregnancy complicated with both placenta previa and prior cesarean. METHODS: Clinical data was obtained from the medical history system at the First Affiliated Hospital of Sun Yat-sen University from February 2003 to December 2016. All cases with a final diagnosis of "placenta previa/low lying placenta (ICD:O44.001-105)" and "scarred uterus complicated with pregnancy (ICD: O34.200-202)" were collected and reviewed. Hysterectomy was taken as the primary outcome; and blood loss was taken as the secondary outcome. RESULTS: Of 219 pregnant women in the final analysis, 25 received a hysterectomy following delivery, and 48 had blood loss exceeding 1000 ml. Pre-surgical risk factors for hysterectomy are ultrasonic signs of vascular lacunae, central placenta previa, and loss of normal hypoechoic retroplacental zone. A pre-surgical predictive equation referred to as "Hysterectomy Index in Placenta Previa with Prior cesarean (HIPs)" was generated and each risk factor was weighted to create an 8-point scale. This index yielded an area under the curve of 0.972 for the prediction of hysterectomy. CONCLUSIONS: Application of the HIPs score may provide an effective pre-surgical prediction of cesarean hysterectomy in pregnant women complicated with both placenta previa and prior cesarean.

Evaluation of Cervical Elastography for Prediction of Spontaneous Preterm Birth in Low-Risk Women: A Prospective Study.

OBJECTIVES: The aim of this study was to determine whether cervical elastographic parameters in addition to cervical length (CL) during the 3 trimesters of pregnancy would be predictive of spontaneous preterm birth (sPTB) among low-risk women. METHODS: This work was a prospective nested case-control study evaluating cervical elastographic parameters and CL in low-risk women during the 3 trimesters of pregnancy. A binary logistic regression analysis was used to calculate significant covariates for prediction of sPTB. The area under the curve of the prediction model was calculated by using a receiver operating characteristic curve. RESULTS: There were 286 women (26 cases and 260 controls) included in the analysis. The parameters of cervical elasticity became softened and heterogeneous during the 3 trimesters of pregnancy in both women with and without sPTB. The differences in the mean strain value at the internal os of the cervix (IOS), ratio (strain ratio of the internal os to the external os) during the second trimester and the IOS during the third trimester between the groups had statistical significance (P < .01; P = .01; P < .01, respectively). The CL had no association with sPTB during the 3 trimesters. The IOS during the second trimester was a better predictor of sPTB, with an area under the curve of 0.730, and sensitivity was 72.73%. CONCLUSIONS: We observed multiple elastographic parameters and demonstrated the physiologic changes in the cervix during the 3 trimesters of pregnancy. Furthermore, we found that the IOS during the second trimester can be helpful in predicting sPTB. However, the CL had no association with sPTB during the 3 trimesters of pregnancy.

Quantitative elastography of cervical stiffness during the three trimesters of pregnancy with a semiautomatic measurement program: A longitudinal prospective pilot study.

AIM: To assess the reproducibility of a semiautomatic quantification tool for cervical stiffness and evaluate the normal changes in cervical elasticity during the three trimesters of pregnancy. METHODS: This longitudinal prospective pilot study evaluated cervical elasticity during the three trimesters of pregnancy (11-14, 20-24 and 28-32 weeks) in women with singleton pregnancies. Women with a history of conization, cerclage, cervical Naboth cysts (diameter > 10 mm), cervical tumors, or uterine malformation were excluded. A semiautomatic tool was used to evaluate the stiffness of the whole cervix and the internal and external cervical os with multiple quantitative elasticity parameters and the cervical length (CL) on the sagittal view via transvaginal elastography. Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to assess intra- and interobserver variability. E-Cervix parameters during the three trimesters were compared using the Friedman test. RESULTS: In total, 217 women with 651 strain examinations during the three trimesters were included. The intra- and interobserver ICC for the E-Cervix parameters ranged from 0.947 to 0.991 and 0.855 to 0.989, respectively. There were significant differences in all parameters among the three trimesters. Cervical elasticity showed significant softening and became heterogeneous during the three trimesters. The median CL was significantly shorter in the first trimester than in the second and third trimesters (P = 0.004, P < 0.001). CONCLUSION: E-Cervix provides a graphical tool for operators to easily define regions of interest and obtain multiple repeatable measures of elasticity. The normal references for E-Cervix parameters during the three trimesters reflect the physiological cervical changes during pregnancy.

Quantitative cervical elastography: a new approach of cervical insufficiency prediction.

OBJECTIVES: To establish methodological criteria for the clinical application of E-cervix technology in non-pregnant women, evaluate cervical differences between non-pregnant CI patients and normal women, and explore the predictive value of E-cervix for CI in non-pregnant women. METHODS: In all, 46 non-pregnant women with CI and 46 non-pregnant women with full-term pregnancy experience were included. Elastic parameters (HR, IOS, EOS, IOS/EOS, CL) of the cervix were measured by transvaginal examination with a mid-sagittal section as the ROI, followed by examination of the whole cervix. The pressure of the probe on the cervix was divided into three levels. The elastic data of three consecutive images were separately obtained by two doctors for three pressure levels. Image stability and the effects of pressure were evaluated and the repeatability of the measurements was tested. In the case and control groups, cervical elasticity images were selected by standardized operation methods. Differences in the parameters between the two groups were determined and the diagnostic efficiency of each parameter was analyzed. RESULTS: The HR, IOS, and EOS showed significant differences when measured on different sequential images obtained by continuous mapping (p < 0.05). The elastic parameters obtained from the first and last two images were significantly different (p < 0.05) and there were no significant differences between the elastic parameters obtained from the last two images (p > 0.05). The HR, IOS, EOS, and IOS/EOS showed significant differences among the pressure levels (p < 0.05), while the IOS showed a significant difference only between grades 0 and 2 (p < 0.05). E-cervix showed good repeatability within and among operators. The elastic parameters obtained by E-cervix in the CI group and control group were significantly different. ROC curve analysis showed that the HR was the most sensitive index for diagnosing CI. CONCLUSION: In E-cervix data acquisition, the first image should be excluded and the probe should not put pressure on the cervix. E-cervix has good retest and inter-observer reliability. Compared with normal women, CI patients showed a relatively softer and shorter cervix. E-cervix can be used as an important diagnostic tool for assessing cervical strain.

Genetic anomalies in fetuses with tetralogy of Fallot by using high-definition chromosomal microarray analysis.

BACKGROUND: The etiology of TOF is complex and the genesis of TOF has been associated with environmental factors and genetic disorders, including chromosomal anomalies, aneuploidies, 22q11.2 deletion and single-gene disease. Previous literatures have shown that a chromosome alteration in about 30% patients with TOF and recently published articles reported that 22q11.2 deletion syndrome accounts for 16% cases with TOF diagnosed postnatally. CMA now is considered as gold standard for detecting genetic anomalies in fetuses with congenital malformations. CMA could detect a 6.6-25% incremental yield of CNVs in CHDs. The aim of this study was to assess the genetic anomalies in fetal tetralogy of Fallot (TOF) by using high-definition CMA. METHODS: This retrospective study reviewed all the fetuses diagnosed with TOF between 2013 and 2018. Prenatal ultrasongraphic findings, including cardiac angle, and the findings of CMA using Affymetrix CytoScan HD array were collected. RESULTS: Ninety-six fetuses with TOF and known genetic results were enrolled. Right aortic arch was the most common associated anomalies (22.9%). One fetus with trisomy 18, one with 46, XX, t (7;10)(q36;q22), one with 47, XYY and five with trisomy 21 were identified. Clinically significant CNVs occurred in 6.8% and uncertain significant CNVs in 3.4% fetal TOF with normal karyotype. A total of four cases with 22q11.2 microdeletion and two fetuses with Yq11.223q11.23 microduplication have been identified. Genetic anomalies, including chromosomal aberrations and pathogenic CNVs, were significantly higher in the TOF with extracardiac anomaly group than in the TOF without extracardiac anomaly group (P = 0.005). Abnormal cardiac angle was noticed in 24.0% fetal TOF. Genetic anomalies were more common in the TOF with abnormal cardiac angle than with normal cardiac angle (P = 0.001). On the other hand, abnormal cardiac angle was noticed in 64.3% fetal TOF with genetic anomalies while abnormal cardiac angle occurred in 17.1% fetal TOF with normal genetic results (P = 0.001). CONCLUSIONS: Genetic testing should be offered, specially using microarray analysis, for the fetal TOF with abnormal cardiac angle or extracardiac defects.

Systemic Venous Drainage Is Associated with an Unfavorable Prenatal Behavior in Fetal Bronchopulmonary Sequestration.

OBJECTIVE: This study aimed to determine the significance of the venous drainage pattern of bronchopulmonary sequestration (BPS) in the prenatal course. METHODS: The venous drainage pattern of fetuses with BPS was determined with high-definition flow and confirmed by postnatal three-dimensional computed tomography angiography scan or autopsy. The volume of BPS lesions during gestation was recorded by the three-dimensional ultrasonographic Virtual Organ Computer-Aided Analysis software. The relationship between venous drainage pattern and prenatal characteristics was determined. RESULTS: Seventy-one fetuses were enrolled: 35 with systemic venous drainage (SVD) and 36 with pulmonary venous drainage (PVD). The volumes of BPS lesions significantly increased from the middle second trimester to the later second trimester in the SVD group. A marked decrease from the later second trimester to the third trimester was observed in the PVD group. The incidences of associated anomalies, hydrops, and polyhydramnios in the SVD group were 14.2, 23.3, and 33.3%, respectively, significantly higher than those in the PVD group (0, 0, and 5.6%, respectively). CONCLUSIONS: Our data indicate that SVD is correlated with a higher risk of associated anomalies and an unfavorable prenatal course in fetal BPS. Identification of the venous drainage pattern is of clinical significance in predicting the prenatal behavior of fetal BPS.

Chromosomal and subchromosomal anomalies associated to small for gestational age fetuses with no additional structural anomalies.

OBJECTIVES: To assess the chromosomal and subchromosomal anomalies in small for gestational age (SGA) fetuses with no additional structural anomalies and their clinical outcomes. METHODS: This study retrospectively reviewed the 128 SGA fetuses with no additional anomalies and underwent genetic testing with karyotyping and chromosomal microarray analysis (CMA). Stratified analysis was performed according to the existence of maternal risk factors for SGA (yes or no), gestational age at onset (before or after 32 weeks), presence of oligohydraminos (yes or no), and umbilical artery Doppler flow (normal or abnormal). RESULTS: Chromosomal anomalies were identified in 6 (4.7%) SGA fetuses and pathogenic subchromosomal anomalies in 4 (3.1%) by microarray analysis. Chromosomal and subchromosomal anomalies were more frequently observed in cases with oligohydraminos (P = .017) and with early-onset SGA (P = .042). No differences were observed in relation to the existence of maternal risk factors and abnormal umbilical artery Doppler flow. Overall survival rate was 75.0% with different rates in the early and the late onset group (P < .001). CONCLUSIONS: There is a 3.3% incremental yield of subchromosomal anomalies in CMA above karyotyping in SGA fetuses. Chromosomal microarray analysis is recommended in SGA fetuses with no additional structural anomalies, especially coexisting with oligohydraminos and being early onset.

Fetal right aortic arch: associated anomalies, genetic anomalies with chromosomal microarray analysis, and postnatal outcome.

OBJECTIVES: The aim of the study was to assess the associated prenatal findings, genetic anomalies with chromosomal microarray analysis (CMA) and postnatal outcome of fetal right aortic arch (RAA). METHODS: This retrospective study reviewed 92 fetuses diagnosed with RAA and the findings of CMA using Affymetrix CytoScan HD array in our institution between 2013 and 2016. RESULTS: Postnatal data were not available for six cases, and genetic data were not available for 26 cases. Tetralogy of the Fallot was the most frequently associated anomaly. Among the 60 fetuses with known karyotype, one was 46, X, Yqh+, der(13)t(8;13)(q22.3;q33.2), one was 47, XYY and the remaining were normal. Our study showed that CMA could detect uncertain significant copy number variants in 5.2% of fetal RAA and pathogenic copy number variants in 5.2%, all of which were microdeletion in chromosome 22q11.21. The genetic anomalies, gestational age at delivery and postnatal death were not significantly different between RAA-no intracardiac anomalies and RAA-intracardiac anomalies group. One infant with aberrant left subclavian artery needed to perform a surgery for respiratory symptom. CONCLUSIONS: A right aortic arch is associated with 22q11.2 deletion syndrome in approximately 5% of cases, and, therefore, prenatal testing, preferably using CMA, should be offered. © 2017 John Wiley & Sons, Ltd.

Chromosomal aneuploidies and copy number variations in posterior fossa abnormalities diagnosed by prenatal ultrasonography.

OBJECTIVE: To explore the genetic aetiology of fetal posterior fossa abnormalities (PFAs). METHODS: This study involved cases of PFAs that were identified by prenatal ultrasonographic screening and confirmed postnatally between January 2012 and January 2016. Conventional cytogenetic analyses and chromosomal microarray analysis were performed, and chromosomal aneuploidies and copy number variations (CNVs) were identified. RESULTS: Among 74 cases included in this study, 8 were of Blake's pouch cyst; 7, Dandy-Walker malformation; 11, vermian hypoplasia; 32, enlarged cisterna magna; and 16, cerebellar hypoplasia. The rates of nonbenign chromosomal aberrations (including chromosomal aneuploidies, pathogenic CNVs, and variants of unknown significance) were 2/8 (25.0%), 2/7 (28.5%), 8/11 (72.7%), 7/32 (21.9%), and 6/16 (37.5%), respectively. Cases were also classified as isolated PFAs (30/74), PFAs with other central nervous system (CNS) abnormalities (13/74), or PFAs with extra-CNS structural abnormalities (31/74). No fetuses with isolated PFAs or PFAs accompanied by other CNS abnormalities exhibited chromosomal aneuploidies or pathogenic CNVs. The rate of pathogenic chromosomal aberrations in the remaining fetuses was 17/31 (22.9%). CONCLUSION: The combined use of chromosomal microarray analysis and karyotype analysis might assist the prenatal diagnosis and management of PFAs, with extra-CNS structural abnormalities being detected by ultrasonography.

Azygos Vein Z Scores in Healthy Fetuses and Fetuses With Venous Malformations Related to the Azygos Vein.

OBJECTIVES: To establish fetal azygos vein and descending aorta sonographic Z score formulas based on femur length and gestational age and to determine the value of azygos vein diameter variation for potential use in the diagnosis of fetal venous malformations related to the azygos vein. METHODS: A total of 452 healthy singleton fetuses and 25 fetuses with venous malformations related to the azygos vein underwent prenatal sonography in this retrospective study. Azygos vein and descending aorta diameters were measured offline after spatiotemporal image correlation volume acquisition. Normal azygos vein and descending aorta Z score formulas were constructed for these measurements based on femur length by performing standard regression analysis followed by weighted regression of absolute residual values. The azygos vein-to-descending aorta ratio was calculated. Three parameters were compared between venous malformations related to the azygos vein and healthy fetuses. RESULTS: Azygos vein and descending aorta Z score formulas were constructed. Both showed a positive linear correlation with femur length (r = 0.79 and 0.90, respectively; P < .01) and gestational age (r = 0.79 and 0.91; P < .01). The azygos vein Z scores and azygos vein-to-descending aorta ratios of fetuses with malformations were significantly higher than those of healthy fetuses (P < .01). In the abnormal group, 96.0% of azygos vein Z scores (24 of 25) were greater than ±2, and 96.0% of azygos vein-to-descending aorta ratios (24 of 25) were greater than the 95% confidence interval. CONCLUSIONS: The azygos vein Z score formulas we developed can provide a quantitative basis for prenatal screening of venous malformations related to the azygos vein. Azygos vein dilatation and an abnormal azygos vein-to-descending aorta ratio may contribute to increasing the recognition of venous malformations involving the azygos vein.

Clinical Outcomes after Selective Fetal Reduction of Complicated Monochorionic Twins with Radiofrequency Ablation and Bipolar Cord Coagulation.

AIMS: To review pregnancy outcomes, complication rates and neonatal neural development of selective termination procedures for complicated monochorionic (MC) twins. METHODS: This was a retrospective review of the pregnancies that underwent selective reduction with radiofrequency ablation (RFA) and bipolar cord coagulation (BCC) in our institution. RESULTS: Forty-eight cases underwent selective reduction with BCC and the remaining 45 with RFA. Overall survival was not statistically different between the RFA and BCC groups (71.1 and 62.5%, p = 0.379). With regard to the indications, the survival rates were not significantly different for twin to twin transfusion syndrome, twin reversed arterial perfusion, discordant anomalies and selective intrauterine growth restriction. Preterm premature rupture of membrane was not statistically different between the BCC and RFA groups (47.9 and 33.3%, p = 0.153). Five foetuses presented with abnormal middle cerebral artery-peak systolic velocity in the BCC group and 4 in the RFA group (p = 0.829). In the BCC group, neurological injury was detected in 2 neonates, presenting with cerebral dysplasia on MR scanning. In the RFA group, intracranial haemorrhage Grade III was detected in one neonate with cranial ultrasound (p = 0.607). CONCLUSIONS: Overall survival and complication rates following selective reduction in complicated MC twin pregnancies is similar irrespective of whether the reduction was performed using RFA or BCC. Key Message: It seems that selective reduction in MC pregnancies with RFA does not carry a significant decrease in the overall survival and complication rates than the cases with BCC. According to our data, neurodevelopmental impairment of the co-twins is relatively seldom after selective reduction.

A rare inherited homozygous missense variant in PLA2G6 influences susceptibility to infantile neuroaxonal dystrophy: a case report.

Background: Infantile neuroaxonal dystrophy (INAD) is an ultra-rare early-onset autosomal recessive neurodegenerative disorder due to PLA2G6 variants. The clinical symptoms of INAD patients display considerable diversity, and many PLA2G6 variants are still not thoroughly investigated in relation to their associated clinical presentations. Case Description: A 16-month-old boy was admitted to our hospital due to regression of acquired motor and speech abilities that had persisted for 4 months. The patient was born to a healthy consanguineous couple after 41 weeks of pregnancy and natural delivery. Before 12 months old, he had normal motor development milestones. On admission, he also showed astasia-abasia, weakness of distal muscles, and diminished patellar tendon reflex. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy. Auditory brainstem response (ABR) indicated moderately severe hearing loss. With chromosome microarray analysis (CMA), we identified several copy number-neutral regions of runs of homozygosity (ROH) in the patient. Whole-exome sequencing (WES) further revealed that the patient harbored a homozygous missense variant NM_003560.2: c.1778C>T, p.Pro593Leu (rs1451486649) in the PLA2G6 gene. In the patient's asymptomatic parents and brother, the PLA2G6 c.1778C>T variant stayed in heterozygous status as confirmed by Sanger sequencing. The patient was finally diagnosed with INAD. Conclusions: We report an INAD child with a rare PLA2G6 c.1778C>T homozygous missense variant and associated clinical symptoms. The family-based cosegregation analysis reveals that the PLA2G6 c.1778C>T homozygous variant contributes to the pathogenesis of INAD.

Loss of keratin 23 enhances growth inhibitory effect of melatonin in gastric cancer.

To investigate the effect of keratin 23 (KRT23) on the anticancer activity of melatonin (MLT) against gastric cancer (GC) cells, microarray analysis was applied to screen differentially expressed genes in AGS GC cells following MLT treatment. Western blotting was used to detect the expression of KRT23 in GC cells and normal gastric epithelial cell line GES­1. KRT23 knockout was achieved by CRISPR/Cas9. Assays of cell viability, colony formation, cell cycle, electric cell­substrate impedance sensing and western blotting were conducted to reveal the biological functions of KRT23­knockout cells without or with MLT treatment. Genes downregulated by MLT were enriched in purine metabolism, pyrimidine metabolism, genetic information processing and cell cycle pathway. Expression levels of KRT23 were downregulated by MLT treatment. Expression levels of KRT23 in AGS and SNU­216 GC cell lines were significantly higher compared with normal gastric epithelial cell line GES­1. KRT23 knockout led to reduced phosphorylation of ERK1/2 and p38, arrest of the cell cycle and inhibition of GC cell proliferation. Moreover, KRT23 knockout further enhanced the inhibitory activity of MLT on the tumor cell proliferation by inhibiting the phosphorylation of p38/ERK. KRT23 knockout contributes to the antitumor effects of MLT in GC via suppressing p38/ERK phosphorylation. In the future, KRT23 might be a potential prognostic biomarker and a novel molecular target for GC.