Induction of labor versus expectant management in patients with idiopathic polyhydramnios.

OBJECTIVE: To evaluate whether induction of labor is associated with lower risk of cesarean section compared to expectant management in patients with isolated polyhydramnios. STUDY DESIGN: This is a single-center, retrospective cohort study of patients with pregnancies complicated by idiopathic polyhydramnios, documented between 34 and 38 weeks gestation, who were delivered between July 2012 and February 2020. The primary outcome was cesarean delivery. Secondary outcomes included chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, and composite neonatal morbidity. RESULTS: There were 194 patients included with idiopathic polyhydramnios - 115 underwent induction and 79 patients were expectantly managed. Planned induction was associated with a lower rate of CD compared with expectant management but did not meet statistical significance (19.1 % vs 30.4 %, aOR 0.51, 95 % CI 0.24, 1.05). A similar effect was seen when stratifying for parity: both nulliparous (9.1 % vs 16.3 %, aOR 0.59, 95 % CI 0.17, 1.98) and multiparous (32.7 % vs 47.2 %, aOR 0.45, 95 % CI 0.18, 1.15) patients had a lower CD rate when there was a planned induction, though neither group met statistical significance. No differences in maternal or fetal secondary outcomes were identified (chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, composite neonatal morbidity). CONCLUSION: Lower rates of cesarean section were associated with labor induction for patients with isolated polyhydramnios, but confidence intervals did not reach statistical significance.

TAVR Beyond Fetal Viability: An Alternative to Preterm Delivery in Symptomatic Severe Aortic Stenosis.

A patient with structural valve degeneration of an aortic bioprosthesis with stenosis stage 3 underwent valve-in-valve transcatheter aortic valve replacement (TAVR) at 29 weeks with improvement. This is the first reported TAVR in the third trimester. TAVR may be an alternative to preterm delivery in cases of symptomatic aortic stenosis.

Postpartum remote home blood pressure monitoring: the new frontier.

There has been an alarming and substantial increase in hypertensive disorders of pregnancy, which are a significant driver of maternal morbidity and mortality. The postpartum period is an especially high-risk time, with >50% of pregnancy-related deaths and significant morbidity occurring during this period. The American College of Obstetricians and Gynecologists suggests inpatient or equivalent monitoring of blood pressures in patients with hypertensive disorders of pregnancy for the immediate 72 hours postpartum and again within 7 to 10 days postpartum. Hypertensive disorders of pregnancy significantly contribute to healthcare costs through increasing admission lengths, rates of readmissions, the number of medications given, and laboratory studies ordered, and through the immeasurable impact on the patient and society. Telemedicine is an essential option for patients with barriers to accessing care, particularly those in remote areas with difficulty accessing subspecialty care, transportation, childcare, or job security. The implementation of these programs also has potential to mitigate racial inequities given that patients of color are disproportionately affected by the morbidity and mortality of hypertensive disorders of pregnancy. Remote blood pressure monitoring programs are generally acceptable, with high levels of satisfaction in the obstetrical population without posing an undue burden of care. Studies have reported different, but encouraging, measures of feasibility, including rates of recruitment, consent, engagement, adherence, and retention in their programs. Considering these factors, the widespread adoption of postpartum blood pressure monitoring programs holds promise to improve the identification and care of this at-risk population. These immediate clinical effects are significant and can reduce short-term hypertension-related morbidity and even mortality, with the potential for long-term benefit with culturally competent, well-reimbursed, and widespread use of these programs. This clinical opinion aims to show that remote monitoring of postpartum hypertensive disorders of pregnancy is a reliable and effective alternative to current follow-up care models that achieves improved blood pressure control and diminishes racial disparities in care while simultaneously being acceptable to providers and patients and cost-saving to hospital systems.

Calculated blood loss at cesarean delivery in patients with preeclampsia with severe features on magnesium sulfate.

INTRODUCTION: Magnesium sulfate decreases the risk of eclampsia in patients with severe preeclampsia. There is a theoretical risk that magnesium sulfate increases the risk of intrapartum hemorrhage. We evaluated whether there was a quantitative difference in blood loss in patients receiving magnesium sulfate at the time of cesarean delivery (CD) compared to those who were not. MATERIALS AND METHODS: A retrospective cohort study was performed using a database of patients with preeclampsia with severe features or eclampsia. The primary outcome was calculated estimated blood loss (cEBL) compared between patients who received magnesium sulfate during CD and those who did not. cEBL was derived through a validated equation by multiplying the patient's blood volume by percent of blood volume loss. Secondary outcomes were hematocrit change, visual EBL (vEBL), hemorrhage, cEBL >1500mL, Apgar <7 at 5 min, and NICU admission. Exclusion criteria were incomplete records or negative cEBL, as well as blood transfusion prior to collection of a postpartum hematocrit. RESULTS: We identified 124 patients with preeclampsia with severe features or eclampsia at time of CD. There were 57 (46%) that received magnesium sulfate during CD and 67 (54%) in which magnesium was stopped during the CD. The mean differences for hematocrit value (0.8, 95% confidence interval (CI) -0.3 to 1.8) and cEBL (108, 95% CI -102 to 318) were not significantly different after adjusting for obesity and history of CD. CONCLUSION: Magnesium sulfate administration for seizure prevention in patients with preeclampsia with severe features at the time of CD does not appear to be associated with an increase in the cEBL.

Intracervical Foley catheter with and without oxytocin for labor induction with Bishop score ≤3: a secondary analysis.

BACKGROUND: The combination method for cervical ripening with a Foley catheter and concurrent oxytocin administration has been shown to reduce the total time from induction to delivery when compared with a Foley catheter only in patients with an unfavorable cervix (Bishop score of <6). It is unclear if this is still effective for patients with a less favorable cervix as indicated by a Bishop score of ≤3. OBJECTIVE: This study aimed to determine if inducing labor with a Foley catheter and concurrent oxytocin administration reduced the total time from induction to delivery in subjects with a Bishop score of ≤3 compared with those who only received a Foley catheter without oxytocin for cervical ripening. STUDY DESIGN: This was a secondary analysis of a randomized, multicenter trial of patients with a live singleton pregnancy at ≥24 weeks' gestation undergoing labor induction with a Foley catheter and a Bishop score of <6. This analysis included patients with a Bishop score of ≤3. Exclusions included >1 cesarean delivery, unexplained bleeding, nonreassuring fetal tracing, major fetal anomalies, or other contraindications for vaginal delivery. The subjects were randomized to receive an intracervical Foley catheter only or with concurrent oxytocin infusion. The primary outcome for this analysis was the time from induction to delivery. Secondary outcomes included delivery at ≤12 hours, time to delivery ≤24 hours, cesarean delivery, total time of oxytocin infusion, need for additional ripening agents, postpartum hemorrhage, chorioamnionitis, and neonatal intensive care unit admission. RESULTS: A total of 322 patients were enrolled in the primary trial; 151 subjects had an initial Bishop score of ≤3 and were included in the secondary analysis (n=77 for Foley catheter with oxytocin and n=74 for the Foley catheter only). The demographics were similar in both groups. Those with a Bishop score of ≤3 who received a Foley catheter with concurrent oxytocin administration had a shorter time from induction to delivery than those patients who received a Foley catheter only for cervical ripening (21.3 vs 27 hours; P=.005). The group with a Foley catheter and oxytocin administered concurrently also had a shorter time from induction to delivery after adjusting for body mass index, parity status, and first Bishop score (21.5 vs 26.7 hours; P=.007). They also were more likely to deliver within 24 hours (74% vs 46%; P=.001) and not to require additional ripening agents (4% vs 15%; P=.04). Patients with the Foley catheter only method were more likely to receive additional ripening agents, but had fewer hours of oxytocin infusion (19.1 vs 12.4 hours; P<.001). There was no difference in the rate of delivery at ≤12 hours, cesarean delivery, postpartum hemorrhage, chorioamnionitis, and neonatal intensive care unit admission. CONCLUSION: Concurrent Foley catheter and oxytocin infusion significantly reduced the time from induction to delivery in patients with a Bishop score of ≤3 when compared with a Foley catheter only, particularly in multiparous patients.

Allosteric Activation of a G Protein-coupled Receptor with Cell-penetrating Receptor Mimetics.

G protein-coupled receptors (GPCRs) are remarkably versatile signaling systems that are activated by a large number of different agonists on the outside of the cell. However, the inside surface of the receptors that couple to G proteins has not yet been effectively modulated for activity or treatment of diseases. Pepducins are cell-penetrating lipopeptides that have enabled chemical and physical access to the intracellular face of GPCRs. The structure of a third intracellular (i3) loop agonist, pepducin, based on protease-activated receptor-1 (PAR1) was solved by NMR and found to closely resemble the i3 loop structure predicted for the intact receptor in the on-state. Mechanistic studies revealed that the pepducin directly interacts with the intracellular H8 helix region of PAR1 and allosterically activates the receptor through the adjacent (D/N)PXXYYY motif through a dimer-like mechanism. The i3 pepducin enhances PAR1/Gα subunit interactions and induces a conformational change in fluorescently labeled PAR1 in a very similar manner to that induced by thrombin. As pepducins can potentially be made to target any GPCR, these data provide insight into the identification of allosteric modulators to this major drug target class.

Structured cyclic peptides that bind the EH domain of EHD1.

EHD1 mediates long-loop recycling of many receptors by forming signaling complexes using its EH domain. We report the design and optimization of cyclic peptides as ligands for the EH domain of EHD1. We demonstrate that the improved affinity from cyclization allows fluorescence-based screening applications for EH domain inhibitors. The cyclic peptide is also unusually well-structured in aqueous solution, as demonstrated using nuclear magnetic resonance-based structural models. Because few EH domain inhibitors have been described, these more potent inhibitors will improve our understanding of the roles of EHD1 in the context of cancer invasion and metastasis.