Streamlined Analysis of Maternal Plasma Indicates Small Extracellular Vesicles are Significantly Elevated in Early-Onset Preeclampsia.

Preeclampsia (PE) is a leading cause of maternal and fetal mortality and morbidity. While placental dysfunction is a core underlying issue, the pathogenesis of this disorder is thought to differ between early-onset (EOPE) and late-onset (LOPE) subtypes. As recent reports suggest that small extracellular vesicles (sEVs) contribute to the development of PE, we have compared systemic sEV concentrations between normotensive, EOPE, and LOPE pregnancies. To circumvent lengthy isolation techniques and intermediate filtration steps, a streamlined approach was developed to evaluate circulating plasma sEVs from maternal plasma. Polymer-based precipitation and purification were used to isolate total systemic circulating maternal sEVs, free from bias toward specific surface marker expression or extensive subpurification. Immediate Nanoparticle Tracking Analysis (NTA) of freshly isolated sEV samples afforded a comprehensive analysis that can be completed within hours, avoiding confounding freeze-thaw effects of particle aggregation and degradation.Rather than exosomal subpopulations, our findings indicate a significant elevation in the total number of circulating maternal sEVs in patients with EOPE. This streamlined approach also preserves sEV-bound protein and microRNA (miRNA) that can be used for potential biomarker analysis. This study is one of the first to demonstrate that maternal plasma sEVs harbor full-length hypoxia inducible factor 1 alpha (HIF-1α) protein, with EOPE sEVs carrying higher levels of HIF-1α compared to control sEVs. The detection of HIF-1α and its direct signaling partner microRNA-210 (miR-210) within systemic maternal sEVs lays the groundwork for identifying how sEV signaling contributes to the development of preeclampsia. When taken together, our quantitative and qualitative results provide compelling evidence to support the translational potential of streamlined sEV analysis for future use in the clinical management of patients with EOPE.

Vaginal Calculus Formation on Exposed Midurethral Sling Mesh.

The presence of a vaginal calculus is a rare clinical entity which may develop in the setting of vaginal urinary stagnation. Numerous factors contribute to stone formation, and management can be complicated by variations in size, location of the stone, and location of adjacent structures. Generally, once diagnosed, vaginal calculi should be removed and surrounding anatomy should be evaluated thoroughly for secondary fistula, erosion, or presence of an instituting foreign body. This report presents a case of vaginal calculus formation on exposed midurethral sling mesh in an elderly patient with hemorrhagic cystitis. This report emphasizes contributing pathophysiology, diagnostic factors, and treatment.

Racial differences in hypertensive disorders in pregnancy during the COVID-19 pandemic.

OBJECTIVE: To compare rates of pregnancy induced hypertensive disorders during the period of the COVID-19 pandemic to prior, baseline years. METHODS: We conducted a retrospective study of 17,742 patients on rates for pregnancy induced hypertensive disorders delivering at 2 local hospitals before (Cohort 1; January 2018 to December 2019; n = 8245) and after (Cohort 2; February 2020 to February 2022; n = 9497) the onset of the COVID-19 pandemic. The primary outcomes were rates of gestational hypertension, pre-eclampsia, and chronic hypertension in patients.Wecompared by year (2018-2022), by patient COVID infection status, and by racial demographics. RESULTS: During the pandemic (Cohort 2), there were lower rates of chronic hypertension (7.4 % vs 6.5 %, p =.02), higher rates of gestational hypertension (26.3 % vs 27.8 %, p =.03), and higher rates of preeclampsia (11.3 % vs 13.1 %, p <.001) compared to years prior to the pandemic (Cohort 1). When evaluating by year, rates of chronic hypertension did not statistically change while rates for preeclampsia increased in the first year of the pandemic and remained high, and rates for gestational hypertension did not increase until the second year of the pandemic. When evaluating by COVID infection status, rates for gestational hypertension were significantly higher for individuals with a positive COVID infection status (COVID negative = 27.4 % vs. COVID positive = 32.8 %; p <.004). Rates of preeclampsia did not differ according to COVID infection status (p = 0.15). CONCLUSION: In this study, rates of pregnancy induced hypertensive disorders increased during the COVID pandemic regardless of COVID infection status.

A Pilot Study of Exposure to Nicotine in Human Pregnancy and Maternal and Fetal Testosterone Levels at Birth.

Nicotine exposure in pregnant rats and sheep has shown a more than 50% increase in female fetal testosterone (FFT) levels. Increased testosterone levels have also been linked to infertility, increased anogenital distance (AGD), and reduced second to fourth digit (2D:4D) finger length ratios (FLR). In humans, we hypothesized that maternal total testosterone (MTT) levels would increase in smoking mothers and would cause increased FFT levels, increased AGD, and decreased 2D:4D FLR. This prospective study separated women expecting a female fetus into nonsmoking and smoking cohorts. Maternal cotinine (MC) was tested at 3rd trimester and delivery to assess nicotine exposure. MTT levels were drawn at delivery, and FFT levels were collected from cord blood. The AGD and 2D:4D FLRs were measured at birth. Data were analyzed using parametric and nonparametric tests. The data of 36 smokers and 28 nonsmokers were analyzed. Smoking mothers had higher parity, drug abuse history and were more likely white race. No statistical differences were seen among the primary outcomes of MTT and FFT. MTT was higher among nonsmokers versus smokers (144 versus 107 ng/dL). No correlations were noted between MC levels at delivery, MTT, and FFT levels. No statistical differences were noted among secondary outcomes of AGD and FLR. Although animal studies showed increased FFT levels after nicotine exposure, this was not seen in our human study. Placental differences in animals and humans may be at work. Our pilot study reveals a need for research on the effects of smoking in pregnancy on fetal hormones.

Cannabis Use Based on Urine Drug Screens in Pregnancy and Its Association With Infant Birth Weight.

OBJECTIVES: This study aims to clarify any association between infant birth weight and cannabis use in pregnancy based on urine drug screens. METHODS: A retrospective medical record review of singleton births from August 2013 through December 2014 with available urine drug screens (UDS) at initiation of prenatal care and delivery was conducted at a large tertiary academic referral center. Patients who used drugs other than cannabis were excluded. RESULTS: The prevalence of cannabis use in pregnancies not complicated by use of other drugs as evidenced by tetrahydrocannabinol in the urine of 2173 patients was 22.6%. Infants born to mothers who tested positive for only tetrahydrocannabinol in urine at both presentation for prenatal care and delivery were of lower median birth weight compared with those who tested negative [2925 g (IQR 2522-3265) vs 3235 g (IQR 2900-3591), P = <0.001]. There was no clinically relevant difference in gestational age at birth [39.0 weeks (IQR 37.1-40.0) vs 39.3 weeks (IQR 38.3-40.0), P = 0.012] between those positive for tetrahydrocannabinol (THC) and those who tested negative. Concomitant tobacco use during pregnancy was not noted to impact infant birth weight using the analysis of covariance. Higher perinatal mortality was observed among those who used cannabis with an adjusted odds ratio of 4.2 (95% CI, 1.53-11.49). CONCLUSIONS: Cannabis use is negatively correlated with fetal birth weight (up to 450 g less) in patients who tested positive for THC when compared with those who did not as documented in the urine drug screens. On the basis of these findings, additional patient education and cessation interventions should be explored with regard to cannabis use in pregnancy.

Improving Patient Safety Event Reporting Among Residents and Teaching Faculty.

BACKGROUND: A June 2012 site visit report from the Accreditation Council for Graduate Medical Education Clinical Learning Environment Review revealed that residents and physicians at TriHealth, Inc., a large, nonprofit independent academic medical center serving the Greater Cincinnati area in Ohio, had an opportunity to improve their awareness and understanding of the hospital's system for reporting patient safety concerns in 3 areas: (1) what constitutes a reportable patient safety event, (2) who is responsible for reporting, and (3) how to use the hospital's current reporting system. METHODS: To improve the culture of patient safety, we designed a quality improvement project with the goal to increase patient safety event reporting among residents and teaching faculty. An anonymous questionnaire assessed physicians' and residents' attitudes and experience regarding patient safety event reporting. An educational intervention was provided in each graduate medical education program to improve knowledge and skills related to patient safety event reporting, and the anonymous questionnaire was distributed after the intervention. We compared the responses to the preintervention and postintervention questionnaires and tracked monthly patient safety event reports for 1 year postintervention. RESULTS: The number of patient safety event reports increased following the educational intervention; however, we saw wide variability in reporting per month. On the postintervention questionnaire, participants demonstrated improved knowledge and attitudes toward patient safety event reporting. CONCLUSION: The goal of this unique project was to increase patient safety event reporting by both residents and teaching faculty in 6 residency programs through education. We achieved this goal through an educational intervention tailored to the institution's new event reporting system delivered to each residency program. We clearly understand that improvements in quality and patient safety require ongoing effort. The keys to ongoing sustainability include (1) developing patient safety faculty and resident experts in each training program to teach patient safety and to be role models, (2) working toward decreasing the barriers to reporting, and (3) providing timely feedback and system changes.