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Ovarian cancer is the second most common gynecologic malignancy, but the most deadly female reproductive cancer in the United States. Epithelial ovarian cancer makes up approximately 90% of all cases and is responsible for more than 90% of ovarian cancer deaths. Elective salpingectomy has been shown to reduce ovarian cancer risk when performed at the time of a benign hysterectomy. Data regarding the risks and benefits of opportunistic bilateral salpingectomy performed at the time of cesarean delivery are limited.We aim to review the current evidence regarding safety and benefits of opportunistic bilateral salpingectomy at the time of cesarean delivery compared with bilateral tubal ligation.Original research articles, review articles, and guidelines on contraception were reviewed.Opportunistic bilateral salpingectomy at the time of cesarean delivery is feasible and safe. Operative time may be increased up to 15 minutes for salpingectomy performed by suture ligation compared with standard tubal ligation. Women with a history of 3 or more cesarean deliveries are more likely to require an alternative procedure. It is important to counsel women that although opportunistic bilateral salpingectomy may significantly decrease the risk of ovarian cancer, it does not eliminate the risk entirely.

Background Multiple guidelines regarding risk stratification for venous thromboembolism (VTE) incidence following cesarean delivery have been promulgated. Objective To estimate the percentage of cesarean delivery patients for which pharmacologic VTE would be recommended and subsequent incidence of VTE, based on several guidelines. Patients/methods This retrospective cohort study used data from the Nationwide Readmissions Database from October 2015 through December 2017. Diagnosis and procedure codes were used to identify patients undergoing cesarean delivery, incidence of VTE, and risk factors used to stratify risk in the existing guidelines. Time-to-event analysis was used to analyze data, stratified by risk categorization in 2011 American College of Gynecology and Obstetrics (ACOG), 2012 American College of Chest Physician (ACCP), 2015 Royal College of Obstetricians and Gynecologists (RCOG) and 2018 American Society for Hematology (ASH) guidelines. Results/conclusions In a cohort of 1,235,149 cesarean deliveries, VTE incidence was 2.1 per 1,000 deliveries at 330 days following delivery (95% confidence interval: 2.0 - 2.2). Proportions of patients that would be recommended for pharmacologic prophylaxis ranged from 0.2% in 2018 ASH guidelines to 73.4% in 2015 RCOG criteria. Among groups considered at elevated risk for VTE for which pharmacologic prophylaxis would be recommended, VTE incidence varied from 35.2 per 1,000 deliveries based on 2018 ASH criteria to 2.5 per 1,000 in 2015 RCOG criteria. In a large cohort of cesarean deliveries in the United States, application of different risk stratification guidelines identified widely different proportions at risk of VTE following delivery, with implications for being categorized as having elevated risk.

Objective As body mass index increases, the risk of postpartum infections has been shown to increase. However, most studies lump women with a body mass index (BMI) of above 40 kg/m2 together, making risk assessment for women in higher BMI categories challenging. The objective of this study was to evaluate the impact of extreme obesity on postpartum infectious morbidity and wound complications during the postpartum period. Study Design The present study is a secondary analysis of women who underwent cesarean delivery and had BMI ≥ 40 kg/m2 in the Maternal-Fetal Medicine Units Cesarean Registry. The primary outcome was a composite of postpartum infectious morbidity including endometritis, wound infection, inpatient wound complication prior to discharge, and readmission due to wound complications. Appropriate statistics used to compare baseline demographics, pregnancy complications, and primary outcomes among women by increasing BMI groups (40–49.9, 50–59.9, 60–69.9, and >70 kg/m2). Results Rates of postpartum infectious morbidity increased with BMI category (11.7% BMI: 50–59.9 kg/m2; 13.7% BMI: 60–69.9 kg/m2; and 21.9% BMI >70+ kg/m2; p = 0.001). Readmission for wound complications also increased with BMI (3.1% for BMI: 50–59.9 kg/m2; 6.2% for BMI: 60–69.9 kg/m2; and 9.4% for BMI >70+ kg/m2; p = 0.001). After adjusting for confounders, increased BMI of 70+ kg/m2 category remained the most significant predictor of postpartum infectious complications compared with women with BMI of 40 to 49.9 kg/m2 (adjusted odds ratio [aOR] = 6.38; 95% confidence interval [CI]: 1.37–29.7). The adjusted odds of readmission also increased with BMI (aOR = 2.33, 95% CI: 1.35–4.02 for BMI 50–59.9 kg/m2; aOR = 4.91, 95% CI: 2.07–11.7 for BMI of 60–69.9 kg/m2; and aOR = 36.2, 95% CI: 7.45–176 for BMI >70 kg/m2). Conclusion Women with BMI 50 to 70+ kg/m2 are at an increased risk of postpartum wound infections and complications compared with women with BMI 40 to 49.9 kg/m2. These data provide increased guidance for counseling women with an extremely elevated BMI and highlight the importance of postpartum wound prevention bundles. Key Points

Objective Pyelonephritis is the most common nonobstetric cause for hospitalization during pregnancy. The maternal and obstetric complications associated with antepartum pyelonephritis are well described. However, it is not clear whether these risks extend into the postpartum period. The primary objective of this study was to describe the morbidity associated with postpartum pyelonephritis, by comparing the morbidity associated with pyelonephritis in the postpartum period to morbidity seen during pregnancy or delivery. Methods A retrospective cohort study was performed using the Nationwide Readmissions Database (NRD), an all-payor sample of discharges from approximately 60% of U.S. hospitalizations. Discharges between October 2015 and December 2018 were included. Maternity-associated hospitalizations, diagnosis of pyelonephritis, comorbid conditions, and incidence of severe maternal morbidity were identified using International Classification of Disease-10th Revision (ICD-10) diagnosis and procedure codes. Bivariate statistics, weighted to account for the complex survey methods in the NRD, were used to evaluate the association between antepartum, delivery, and postpartum hospital stays associated with pyelonephritis and maternal morbidity. Weighted regression models were used to evaluate the association between admission timing and maternal outcomes. Results A total of 32,850 pyelonephritis admissions were identified, corresponding to a national estimate of 61,837 admissions. Of these, 1,465 (2.4%) were postpartum, 55,056 (89.0%) were antepartum, and 5,317 (8.6%) involved a delivery stay. Rates of severe maternal morbidity were higher in the postpartum group than the antepartum or delivery hospitalization groups (59.5 vs. 12.9 and 15.8%, respectively, p Conclusion Though relatively uncommon, postpartum hospitalizations for pyelonephritis are associated with higher rates of severe maternal morbidity, driven by differential rates of sepsis, than are antepartum or delivery-associated hospitalizations.

Background Infective endocarditis (IE) is a rare but serious infection that complicates pregnancy. Little is known about IE management and outcomes in this population. Methods The National Readmissions Database was used to obtain data between October 2015 and October 2018. Billing codes identified admissions for IE in female patients of reproductive age. Demographic characteristics, comorbidities, and outcomes were compared between patients with maternity-associated and nonmaternity-associated IE and obstetric patients who delivered with and without IE. Weighted regressions were used to examine outcomes in adjusted models. Results We identified 12 602 reproductive-aged female patients with a diagnosis of IE, of which 382 (weighted national estimate, 748) were maternity-associated. Of these cases, 117 (weighted national estimate, 217) occurred during a delivery admission. Compared with patients with nonmaternity-associated IE, maternity-associated infection was associated with younger age (mean, 29.0 vs 36.6 years; P < .001), Medicaid coverage (72.5% vs 47.2%; P < .001), and drug use (76.2% vs 59.8%; P < .001). Mortality was comparable (8.1% vs 10.6%; adjusted rate ratio [aRR], 1.03; 95% confidence interval [CI]: .71–1.48). Compared with patients who delivered without IE, IE complicating delivery was associated with worse maternal and fetal outcomes, including maternal mortality (17.2% vs Conclusions Maternity-associated IE does not appear to confer additional risk for adverse outcome over nonmaternity-associated infection. Patients who deliver with IE have worse maternal and fetal outcomes than those whose deliveries are not complicated by IE.

OBJECTIVE Individuals with Impostor Phenomenon (IP) believe they have achieved success by fooling others into thinking they are intelligent/capable and fear they will be discovered. This fear has been shown to cause psychological distress and may affect OB/GYN training. The objective of this study was to investigate the prevalence of IP and correlation with anxiety among OB/GYN trainees and faculty. DESIGN/SETTING An anonymous cross-sectional survey including a demographic questioner, Clance Impostor Scale, and Generalized Anxiety Disorder 2-items screening tool was distributed to 200 attendees at the 2019 American College of Obstetricians and Gynecologists Annual Meeting. PARTICIPANTS Eighty-nine medical students, 38 residents, 3 fellows, and 9 attendings completed the survey for a response rate of 72%. RESULTS The average participant experienced frequent feelings of IP with the mean score of 65 ± 18. Nine (8%) experienced few feelings of IP, 27 (24%) had moderate IP feelings, 55 (50%) had frequent IP feelings, and 20 (18%) had intense IP feeling. There was no difference between IP score and trainee/faculty gender, race, or region of country. The degree of IP was significantly associated with level of medical training with more experienced physicians scoring lower than trainees (F = 6.07, p = 0.001). Finally, an association was found between anxiety and IP; individuals with a positive GAD-2 screen had significantly more feelings of IP compared to individuals with a negative GAD-2 screen (t = 4/79, p CONCLUSION This study suggests that IP is likely prevalent among OB/GYN trainees and correlate with anxiety. Further discussion is needed regarding the impact of IP on medical education training and career advancement in the field of OB/GYN and other surgical specialties.

Background Little is known about infective endocarditis (IE) occurring during pregnancy. In this analysis, we sought to define the patient characteristics, risk factors, and outcome of maternity-associated IE (maIE). Methods The National Readmissions Database was used to identify admissions for IE in female patients aged 12 – 55 years discharged between Oct. 2015 and Dec. 2017. Demographics, comorbidities, and outcomes were obtained. Differences between groups were analyzed using weighted Chi-squared test for categorical variables and weighted linear regression for continuous variables. Weighted multivariate regressions adjusted for demographics, hospital, etiologic organism, and comorbid conditions to assess the association between maternity status and outcomes. Results Out of 10,271 identified IE admissions (corresponding to a national estimate of 19,626 admissions), maIE accounted for 320 (national estimate 617) (3.1%). Of these maIE admissions, 41.2% were antepartum admissions, 26.3% resulted in delivery, 18.3% were postpartum, and 11.3% were an early or abnormal pregnancy. Patients with maIE were younger (28.4 ± 3.9 vs. 36.6 ± 8.0, P < 0.001) and more likely insured by Medicaid (73.3% vs. 46.6%, P < 0.001). Although generally healthier, patients with maIE had higher rates of drug abuse (75.7% vs. 58.5%, P < 0.001). In unadjusted comparisons maIE was associated with lower rates of 60-day mortality and thromboembolic events. In adjusted analysis only differences between rates of thromboembolic events were significant (adjusted incremental difference: -17.1%, 95% confidence interval: -22.7% to -11.6%). Differences in rates of valve procedures, mechanical ventilation, length of stay, and inpatient costs were not statistically significant (Figure). Regression-adjusted Outcomes Conclusion Compared with other reproductive aged female IE patients, patients with maIE are younger, healthier, more likely insured by Medicaid, and report higher rates of drug abuse. After adjustment, they receive similar management and do not appear to be at higher risk for adverse outcomes including mortality. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

Background Infective endocarditis (IE) is a rare but serious complication of pregnancy. Its impact on delivery outcomes is unknown. In this study, we use a national administrative database to compare outcomes of deliveries complicated by IE to non-IE deliveries. Methods The National Readmissions Database was used to identify discharges between Oct. 2015 and Dec. 2017 for deliveries in patients aged 12 – 55 years with concomitant IE, which were compared to those deliveries without IE. Demographics, comorbidities, and outcomes were obtained. Differences between groups were analyzed using weighted Chi-squared test for categorical variables and weighted linear regression for continuous variables. Weighted multivariate regression models adjusted for demographic, facility, and comorbidity conditions were used to evaluate the association between IE and delivery outcomes. Results We identified 88 individuals with IE complicating their delivery hospitalization, corresponding to a national estimate of 162 admissions during the study period, who were compared to 4,401,879 delivery hospitalizations not complicated by IE (weighted national estimate 8,375,536). Patients with IE were more likely to reside in ZIP codes with median incomes in the lowest national quartile (46.3% vs. 28.1%, P = 0.003) and were more likely to be insured by Medicaid (76.5% vs. 42.1%, P < 0.001). Rates of pre-existing cardiac valve disease (39.9% vs. 0.2%, P < 0.001) and congenital heart disease (6.6% vs 0.1%, P < 0.001) were higher in those with IE, as well as drug abuse (69.3% vs. 2.6%, P < 0.001). Unadjusted analyses demonstrated higher rates of in-hospital mortality for IE-associated admissions (12.1% versus 0.005%), along with high rates of severe maternal morbidity, stillbirth, preterm birth, and cesarean birth, and longer lengths of stay and total hospital costs. These differences persisted despite adjustment using multivariate methods (Table). Clinical and Resource Utilization Outcomes Conclusion The presence of IE during an admission for delivery is associated with poorer outcomes for both pregnant patients and their fetuses. The occurrence of IE during pregnancy was associated with lower income, a history of cardiac disease, and drug abuse. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

Exosomes are small vesicles ranging in size from 30 nm to 100 nm that are released both constitutively and upon stimulation from a variety of cell types. They are found in a number of biological fluids and are known to carry a variety of proteins, lipids, and nucleic acid molecules. Originally thought to be little more than reservoirs for cellular debris, the roles of exosomes regulating biological processes and in diseases are increasingly appreciated. Several methods have been described for isolating exosomes from cellular culture media and biological fluids. Due to their small size and low density, differential ultracentrifugation and/or ultrafiltration are the most commonly used techniques for exosome isolation. However, plasma of HIV-1 infected individuals contains both exosomes and HIV viral particles, which are similar in size and density. Thus, efficient separation of exosomes from HIV viral particles in human plasma has been a challenge. To address this limitation, we developed a procedure modified from Cantin et. al., 2008 for purification of exosomes from HIV particles in human plasma. Iodixanol velocity gradients were used to separate exosomes from HIV-1 particles in the plasma of HIV-1 positive individuals. Virus particles were identified by p24 ELISA. Exosomes were identified on the basis of exosome markers acetylcholinesterase (AChE), and the CD9, CD63, and CD45 antigens. Our gradient procedure yielded exosome preparations free of virus particles. The efficient purification of exosomes from human plasma enabled us to examine the content of plasma-derived exosomes and to investigate their immune modulatory potential and other biological functions.

Exosomes are small membrane-bound vesicles secreted by cells that function to shuttle RNA and proteins between cells. To examine the role of exosomal micro RNA (miRNA) during the early stage of HIV-1 infection we characterized miRNA in exosomes from HIV-infected macrophages, compared with exosomes from non-infected macrophages. Primary human monocytes from uninfected donors were differentiated to macrophages (MDM) which were either mock-infected or infected with the macrophage-tropic HIV-1 BaL strain. Exosomes were recovered from culture media and separated from virus particles by centrifugation on iodixanol density gradients. The low molecular weight RNA fraction was prepared from purified exosomes. After pre-amplification, RNA was hybridized to microarrays containing probes for 1200 miRNA species of known and unknown function. We observed 48 miRNA species in both infected and uninfected MDM exosomes. Additionally, 38 miRNAs were present in infected-cell exosomes but not uninfected-cell exosomes. Of these, 13 miRNAs were upregulated in exosomes from HIV-infected cells, including 4 miRNA species that were increased by more than 10-fold. Though numerous miRNA species have been identified in HIV-infected cells, relatively little is known about miRNA content in exosomes from these cells. In the future, we plan to investigate whether the upregulated miRNA species we identified are increased in exosomes from HIV-1-positive patients.

CD4+ T cell depletion and immune activation are hallmarks of HIV infection. Despite extensive studies, the mechanisms underlying immune modulation remain elusive. HIV-1 Nef protein is secreted in exosomes from infected cells and is abundant in the plasma of HIV+ individuals. Exosomal Nef (exNef) was also shown to induce apoptosis in bystander CD4+ T cells. We hypothesized that exNef contributes to HIV pathogenesis. A HIV-1 NL4-3 virus containing alanine substitutions in the secretion modification region (SMR; amino acids 66 to 70; HIVNefsmr5a) was developed. Nef protein containing this modified SMR was shown to be deficient in exNef secretion in nef-transfected cells. Using both HIV-1 NL4-3 wild type (HIVwt) and HIVNefsmr5a, correlates of pathogenesis were evaluated in cell-lines, human peripheral blood mononuclear cells, and humanized NOD-RAG1 -/- IL2r -/- double mutant (NRG) mice. Disruption of the SMR did not affect viral replication or exNef secretion from infected cell cultures as compared with nef-transfected cells. However, T cell apoptosis was reduced in HIVNefsmr5a infected cell cultures and CD4+ T cell depletion was reduced in the spleen and peripheral blood of similarly infected NRG mice. Inflammatory cytokine release was also decreased in the sera of HIVNefsmr5a infected mice relative to HIVwt infected controls. These findings demonstrate the importance of Nef and the SMR motif in HIV pathogenesis and suggest a potential role for exNef in HIV-driven immune modulation

Chronic immune activation is one of the strongest predictors of human immunodeficiency virus (HIV) disease progression, associated with chronic levels of detectable cytokines and elevated expression of activation markers on the surface of T lymphocytes [1–3]. Despite extensive studies highlighting direct and indirect viral induction of chronic immune activation, the mechanisms underlying the chronically activated immune state during HIV infection are not fully elucidated. Exosomes are small membrane delimited vesicles released both constitutively and on stimulation from a variety of cell types [4]. They are found in a number of biological fluids and are known to carry a variety of proteins and nucleic acid molecules [4]. Although they were originally thought to be little more than reservoirs for cellular debris, their role in regulating biological functions as well as disease is increasingly appreciated [4]. In this study, exosomes isolated from the plasma of HIV-infected individuals were analyzed for cytokine and chemokine content compared with exosomes from uninfected controls and assessed for immunomodulatory potential on bystander CD4+ and CD8+ T cells.