Prenatal diagnosis of polycystic kidney caused by biallelic hypomorphic variants in the PKD1 gene.

Heterozygous loss-of-function variants in the PKD1 gene are commonly associated with adult-onset autosomal dominant polycystic kidney disease (ADPKD), where the formation of renal cysts depends on the dosage of the PKD1 gene. Biallelic null PKD1 variants are not viable, but biallelic hypomorphic variants could lead to early-onset PKD. We report a non-consanguineous Chinese family with recurrent fetal polycystic kidney and negative findings in the coding region of the PKHD1 gene or chromosomal microarray analysis. Trio exome analysis revealed compound heterozygous variants of uncertain significance in the PKD1 gene in the index pregnancy: a novel paternally inherited c.7863 + 5G > C and a maternally inherited c.9739C > T, p.(Arg3247Cys). Segregation analysis through long-range PCR followed by nested PCR and Sanger sequencing confirmed another affected fetus had both variants, while the other two normal siblings and the parents carried either variant. Thus, these two variants, both of which were hypomorphic as opposed to null variants, co-segregated with prenatal onset polycystic kidney disease in this family. Functional studies are needed to further determine the impact of these two variants. Our findings highlight the biallelic inheritance of hypomorphic PKD1 variants causing prenatal onset polycystic kidney disease, which provides a better understanding of phenotype-genotype correlation and valuable information for reproductive counseling.

A critical evaluation of the external and internal maneuvers for resolution of shoulder dystocia.

In the management of shoulder dystocia, it is often recommended to start with external maneuvers, such as the McRoberts maneuver and suprapubic pressure, followed by internal maneuvers including rotation and posterior arm delivery. However, this sequence is not based on scientific evidence of its success rates, the technical simplicity, or the related complication rates. Hence, this review critically evaluates the success rate, technique, and safety of different maneuvers. Retrospective reviews showed that posterior arm delivery has consistently higher success rates (86.1%) than rotational methods (62.4%) and external maneuvers (56.0%). McRoberts maneuver was thought to be a simple method, however, its mechanism is not clear. Furthermore, McRoberts position still requires subsequent traction on the fetal neck, which presents a risk for brachial plexus injury. The 2 internal maneuvers have anatomic rationales with the aim of rotating the shoulders to the wider oblique pelvic dimension or reducing the shoulder width. The techniques are not more sophisticated and requires the accoucher to insert the correct hand (according to fetal face direction) through the more spacious sacro-posterior region and deep enough to reach the fetal chest or posterior forearm. The performance of rotation and posterior arm delivery can also be integrated and performed using the same hand. Retrospective studies may give a biased view that the internal maneuvers are riskier. First, a less severely impacted shoulder dystocia is more likely to have been managed by external maneuvers, subjecting more difficult cases to internal maneuvers. Second, neonatal injuries were not necessarily caused by the internal maneuvers that led to delivery but could have been caused by the preceding unsuccessful external maneuvers. The procedural safety is not primarily related to the nature of the maneuvers, but to how properly these maneuvers are performed. When all these maneuvers have failed, it is important to consider the reasons for failure otherwise repetition of the maneuver cycle is just a random trial and error. If the posterior axilla is just above the pelvic outlet and reachable, posterior axilla traction using either the accoucher fingers or a sling is a feasible alternative. Its mechanism is not just outward traction but also rotation of the shoulders to the wider oblique pelvic dimension. If the posterior axilla is at a higher sacral level, a sling may be formed with the assistance of a long right-angle forceps, otherwise, more invasive methods such as Zavanelli maneuver, abdominal rescue, or symphysiotomy are the last resorts.

Dissection of PIK3CA Aberration for Cervical Adenocarcinoma Outcomes.

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient's circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women's cancer.

Umbilical cord prolapse: revisiting its definition and management.

Umbilical cord prolapse is an unpredictable obstetrical emergency with an incidence ranging from 1 to 6 per 1000 pregnancies. It is associated with high perinatal mortality, ranging from 23% to 27% in low-income countries to 6% to 10% in high-income countries. In this review, we specifically addressed 3 issues. First, its definition is not consistent in the current literature, and "occult cord prolapse" is a misnomer because the cord is still above the cervix. We proposed that cord prolapse, cord presentation, and compound cord presentation should be classified according to the positional relationship among the cord, the fetal presenting part, and the cervix. All of them may occur with either ruptured or intact membranes. The fetal risk is highest in cord prolapse, followed by cord presentation, and lastly by compound cord presentation, which replaces the misnomer "occult cord prolapse." Second, the mainstay of treatment of cord prolapse is urgent delivery, which means cesarean delivery in most cases, unless vaginal delivery is imminent. The urgency depends on the fetal heart rate pattern, which can be bradycardia, recurrent decelerations, or normal. It is most urgent in cases with bradycardia, because a recent study showed that cord arterial pH declines significantly with the bradycardia-to-delivery interval at a rate of 0.009 per minute (95% confident interval, 0.0003-0.0180), and this may indicate an irreversible pathology such as vasospasm or persistent cord compression. However, cord arterial pH does not correlate with either deceleration-to-delivery interval or decision-to-delivery interval, indicating that intermittent cord compression causing decelerations is reversible and less risk. Third, while cesarean delivery is being arranged, different maneuvers should be adopted to relieve cord compression by elevating the fetal presenting part and to prevent further cord prolapse beyond the vagina. A recent study showed that the knee-chest position provides the greatest elevation effect, followed by filling of the maternal urinary bladder with 500 mL of fluid, and then the Trendelenburg position (15°) and other maneuvers. However, each maneuver has its own advantages and limitations; thus, they should be applied wisely and with great caution, depending on the actual clinical situation. Therefore, we have proposed an algorithm to guide this acute management.

Bradycardia-to-delivery interval and fetal outcomes in umbilical cord prolapse.

INTRODUCTION: Umbilical cord prolapse is a major obstetric emergency associated with significant perinatal complications. However, there is no consensus on the optimal decision-to-delivery interval, as many previous studies have shown poor correlation between the interval and umbilical cord arterial blood gas or perinatal outcomes. We aim to investigate whether bradycardia-to-delivery or decision-to-delivery interval was related to poor cord arterial pH or adverse perinatal outcome in umbilical cord prolapse. MATERIAL AND METHODS: This was a retrospective study conducted at a university tertiary obstetric unit in Hong Kong. All women with singleton pregnancy complicated by cord prolapse during labor between 1995 and 2018 were included. Women were categorized into three groups. Group 1: persistent bradycardia; Group 2: any type of decelerations without bradycardia; and Group 3: normal fetal heart rate. The main outcome was cord arterial blood gas results of the newborns in different groups. Maternal demographic data and perinatal outcomes were reviewed. Correlation analysis between cord arterial blood gas result and time intervals including bradycardia-to-delivery, deceleration-to-delivery, and decision-to-delivery were performed for the different groups with Spearman test. RESULTS: There were 34, 30, and 50 women in Groups 1, 2, and 3, respectively. Cord arterial pH and base excess did not correlate with decision-to-delivery interval in any of the groups, but they were inversely correlated with bradycardia-to-delivery interval in Group 1 (Spearman's ρ = -.349; P = .043 and Spearman's ρ = -.558; P = .001, respectively). The cord arterial pH drops at 0.009 per minute with bradycardia-to-delivery interval in Group 1 (95% CI 0.0180-0.0003). The risk of significant acidosis (pH < 7) was 80% when bradycardia-to-delivery interval was >20 minutes, and 17.2% when the interval was <20 minutes. CONCLUSIONS: There is significant correlation between bradycardia-to-delivery interval and cord arterial pH in umbilical cord prolapse with fetal bradycardia but not in cases with decelerations or normal heart rate. The drop of cord arterial pH is rapid and urgent delivery is essential in such situations.

Prevalence and impact of hepatitis B virus infection in ovarian cancer patients in an endemic area-A retrospective cohort study.

Hepatitis B virus (HBV) infection is associated with many extrahepatic malignancies, but its association with and impact on ovarian cancer has not been examined. We therefore examined the prevalence of HBV infection among women with primary ovarian carcinoma in an endemic area, and whether this impacts the presentation and survival of these patients. In a retrospective study, we reviewed 523 patients presenting with primary ovarian cancer and known HBV status between 1 January 2006 and 31 December 2017. Patients were divided into HBV-positive and negative groups for the comparison of the patient characteristics and presentation, including staging and histological types, and short term (2 years) mortality from ovarian cancer. Among the 10.1% (53/523) patients screened positive for HBV, more of them presented with advanced staging at FIGO stage 3 or above (OR 1.378, 95% CI 1.063-1.787), although there were no significant differences in patient characteristics. Within 24 months from presentation, there were more deaths due to malignancy in the HBV-positive group (73.3% vs 44.2%, OR 1.659, 95% CI 1.135-2.425). On multivariate analysis after adjusting for nulliparity status, previous use of oestrogens, presence of metastases, histological type (epithelial or others) and grading (high grade or not), whether optimal debulking was performed, and chemotherapy, HBV infection was independently associated with increased death within 24 months of presentation (aOR 2.683, 95% CI 1.015-7.091). In conclusion, the findings of this study suggested an adverse effect of chronic HBV infection on survival within two years of presentation in patients with primary ovarian cancer.

Trends in serum human chorionic gonadotropin levels 0-4 days after methotrexate administration for predicting tubal ectopic pregnancy treatment success.

OBJECTIVE: To evaluate serum human chorionic gonadotropin (HCG) levels 0-4 days after single-dose methotrexate administration for tubal ectopic pregnancy. METHODS: The present retrospective study included women with tubal ectopic pregnancy treated by methotrexate at a tertiary hospital in Hong Kong, China, between January 1, 2007, and December 31, 2016. Patients were stratified serum HCG levels rose or fell from day 0-4 post-administration. Trends in day 0-4 serum HCG to predict treatment success were compared with that of day 4-7 serum HCG. The optimal drop in HCG was identified by receiver operating characteristic curve analysis. RESULTS: There were 102 patients included. The positive predictive value (PPV) of day 0-4 serum HCG for treatment success was 91% (95% confidence interval [CI] 82-96), which is comparable to the current criterion of a 15% drop in day 4-7 serum HCG (PPV 91%, 95% CI 84-95). A 6% drop in day 0-4 serum HCG was the best predictor of treatment success (PPV 96%, 95% CI 86-99). CONCLUSION: A drop in day 0-4 serum HCG provided earlier prognostic information and was not inferior to the current criterion.