Endometrioid carcinomas with sex cord-like formations and hyalinization: spontaneous pregnancy after conservative treatment.

Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus, or corded and hyalinized endometrioid adenocarcinoma (CHEC), is a rare morphological variant of endometrioid carcinoma, for which there is limited literature and few cases reports. Most researchers tend to consider CHEC as a low-grade cancer with a favorable prognosis. Full-staging surgery is the primary choice for this disease, and no case of CHEC has been previously reported to be treated conservatively. Here, we present the following case to explore the possibility of fertility-preserving treatment for young women with CHEC. A 23-year-old nulliparous patient diagnosed with presumed stage IA CHEC received fertility-sparing treatment at the Obstetrics and Gynecology Hospital of Fudan University and got a complete response (CR) after 10 months of conservative treatment. The patient subsequently became pregnant spontaneously, successfully conceived, and gave birth to a healthy male neonate without any sign of recurrence during 37 months follow-up after CR. The patient's postpartum follow-up is continuing. Presently, CHEC is not included in the fertility-sparing field of any available guidelines. This case indicates that fertility-sparing treatment may be an option for highly selected patients with CHEC. Continuous follow-up remains mandatory to observe long-term outcomes.

The pregnancy and oncology outcome of fertility-sparing management for synchronous primary neoplasm of endometrium and ovary.

PURPOSE: To investigate the efficacy of fertility-preserving treatment for young women with synchronous primary neoplasm of endometrium and ovary. METHODS: We retrospectively reviewed eight patients with concurrent primary grade 1 presumed stage IA endometrioid endometrial adenocarcinoma (EEA) or endometrial atypical hyperplasia (EAH) and primary stage I ovarian tumors who underwent fertility-sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between April 2016 and December 2022. RESULTS: Synchronous endometrial and ovarian cancers (SEOC) accounted for 50% of these eight patients. The median age of patients was 30.5 years (range, 28-34 years). None of them received chemotherapy. The median treatment time was 4 months (range, 3-8 months). 87.5% (7/8) cases achieved complete response (CR), and the median time to CR was 3.8 months (range, 1.5-7.7 months). Among patients who got CR, none of them showed any signs of recurrence. Pregnancies and successful deliveries were achieved in 4 of 5 patients. Till September 2023, the median follow-up period was 50.5 months (range:15.2-85.2 months). CONCLUSION: Fertility-sparing treatment is feasible for highly selected patients with synchronous neoplasm of the endometrium and ovary, but strict screening and monitoring are mandatory. Though the results of our limited cases are encouraging, long follow-up and more clinical data are required. Enrolled patients must be fully informed of the risks during conservative treatment.

Endometrium-derived mesenchymal stem cells suppress progression of endometrial cancer via the DKK1-Wnt/ß-catenin signaling pathway.

BACKGROUND: Mesenchymal stem cell (MSC) therapy is an attractive treatment option for various cancers. Whether MSCs can be used to treat well-differentiated endometrial cancer (EC) remains unclear. The aim of this study is to explore the potential therapeutic effects of MSCs on EC and the underlying mechanisms. METHODS: The effects of adipose-derived MSCs (AD-MSCs), umbilical-cord-derived MSCs (UC-MSCs), and endometrium-derived MSCs (eMSCs) on the malignant behaviors of EC cells were explored via in vitro and in vivo experiments. Three EC models, including patient-derived EC organoid lines, EC cell lines, and EC xenograft model in female BALB/C nude mice, were used for this study. The effects of MSCs on EC cell proliferation, apoptosis, migration, and the growth of xenograft tumors were evaluated. The potential mechanisms by which eMSCs inhibit EC cell proliferation and stemness were explored by regulating DKK1 expression in eMSCs or Wnt signaling in EC cells. RESULTS: Our results showed that eMSCs had the highest inhibitory effect on EC cell viability, and EC xenograft tumor growth in mice compared to AD-MSCs and UC-MSCs. Conditioned medium (CM) obtained from eMSCs significantly suppressed the sphere-forming ability and stemness-related gene expression of EC cells. In comparison to AD-MSCs and UC-MSCs, eMSCs had the highest level of Dickkopf-related protein 1 (DKK1) secretion. Mechanistically, eMSCs inhibited Wnt/ß-catenin signaling in EC cells via secretion of DKK1, and eMSCs suppressed EC cell viability and stemness through DKK1-Wnt/ß-catenin signaling. Additionally, the combination of eMSCs and medroxyprogesterone acetate (MPA) significantly inhibited the viability of EC organoids and EC cells compared with eMSCs or MPA alone. CONCLUSIONS: The eMSCs, but not AD-MSCs or UC-MSCs, could suppress the malignant behaviors of EC both in vivo and in vitro via inhibiting the Wnt/ß-catenin signaling pathway by secreting DKK1. The combination of eMSCs and MPA effectively inhibited EC growth, indicating that eMSCs may potentially be a new therapeutic strategy for young EC patients desiring for fertility preservation.

Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: A prospective, open-label, randomized controlled phase II study.

OBJECTIVE: To compare the effects of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility-preserving treatment in patients with atypical endometrial hyperplasia (AEH). METHODS: This was a single-center phase II study with an open-label, randomized, controlled trial conducted between July 2017 and June 2020 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to the MA (N = 60), LNG-IUS (N = 60), or MA + LNG-IUS (N = 60) groups, in which the patients received MA (160 mg orally daily), LNG-IUS, or MA + LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. The primary endpoint was complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were CR rate at 32 weeks of treatment, adverse events, and recurrence and pregnancy rates. All analyses were conducted in a modified intention to treat (ITT) population who underwent randomization and in whom treatment was initiated. RESULTS: The Kaplan-Meier estimate of 16-week CR rates (with 95% confidence interval) were 19.2% (9.0-29.4%) in the MA group, 35.0% (22.8-47.2%) in the LNG-IUS group, and 29.4% (17.2-41.6%) in the MA + LNG-IUS groups. Side effects such as weight gain, increased nocturnal urine, night sweat, insomnia and edema face seemed to occur less frequently in LNG-IUS group compared with MA group. No difference was found among groups regarding second endpoints. CONCLUSIONS: LNG-IUS or LNG-IUS plus MA did not show significant therapeutic benefit compared with MA alone. Further studies including sufficient sample-size are needed to validate these findings due to the underpowered design of this trial. FUNDING: This study was supported by the National Key Research and Development Program of China (Grant No 2019YFC1005200 and 2019YFC1005204), Shanghai Medical Centre of Key Programs for Female Reproductive Diseases (Grant No. 2017ZZ010616), Shanghai sailing program (Grant No. 19YF1404200), and Shen Kang clinical project (SHDC22021219). Trial registrationClinicalTrials.govNCT03241888. https://www. CLINICALTRIALS: gov/ct2/show/NCT03241888?term=NCT03241888&draw=2&rank=1.

Socioeconomic disparities in fertility treatments and associated likelihood of livebirth following in vitro fertilization.

OBJECTIVE: To determine whether neighborhood-level socioeconomic characteristics are associated with the likelihood of livebirth (LB) following in vitro fertilization (IVF). Specifically, we evaluated neighborhood-level household income, unemployment rate, and educational attainment. DESIGN: A retrospective cross-sectional study was conducted for patients undergoing autologous IVF cycles. SETTING: Large academic health system. INTERVENTIONS: For each patient, ZIP code of residence was used as a proxy for neighborhood. Neighborhood characteristics were compared between patients with and without LB. Generalized estimating model was used to adjust the association between SES factors and likelihood of a live birth with respect to relevant clinical factors. RESULTS: A total of 4942 autologous IVF cycles from 2768 patients were included: 1717 (62.0%) had at least one associated LB. Patients who achieved LB from IVF were younger, had higher anti-Mullerian hormone (AMH) levels, lower body mass index (BMI), and differed by ethnic background, primary language, and neighborhood socioeconomic characteristics. In a multivariable model, language, age, AMH, and BMI were associated with a live birth from IVF. None of the neighborhood-level socioeconomic variables were associated with the total number of IVF cycles or cycles required to achieve first LB. CONCLUSION: Patients living in neighborhoods with lower annual household income have lower odds of livebirth after IVF compared to those living in more affluent areas, despite undergoing the same number of IVF stimulation cycles.

PTEN mutation predicts unfavorable fertility preserving treatment outcome in the young patients with endometrioid endometrial cancer and atypical hyperplasia.

OBJECTIVE: This study aimed to investigate the impact of molecular classification and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment in the patients with endometrioid endometrial cancer (EEC) and endometrial atypical hyperplasia (EAH). METHODS: This is a single-center retrospective study. A total of 135 patients with EEC and EAH receiving fertility-preserving treatment and molecular classification were reviewed. The distribution of the four types of molecular classification was described. The impact of non-specific molecular profile (NSMP), mismatch repair-deficiency (MMRd), and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment was analyzed. RESULTS: Of the patients analyzed, 86.7% (117/136) were classified as having NSMP; 14 (10.4%), MMRd; 1 (0.7%), POLEmut EAH; and 3 (2.2%), p53abn EEC. The patients having NSMP and MMRd achieved similar 16-, 32-, and 48-week complete response rates. The patients harboring tier I and tier II PTEN mutations (PTENmut-Clin) achieved lower cumulative 32-week CR rates than those with PTEN-others (without PTENmut-Clin) (22/47, 46.8% vs. 50/74, 67.6%; p=0.023; odds ratio=0.422; 95% confidence interval [CI]=0.199-0.896). Insulin-resistance (hazard ratio [HR]=0.435; 95% CI=0.269-0.702; p=0.001) and PTENmut-Clin (HR=0.535; 95% CI=0.324-0.885; p=0.015) were independent negative predictors for lower 32-week CR rates. CONCLUSION: PTENmut-Clin is an independent risk factor for unfavorable fertility-preserving treatment outcomes in the patients with EEC and EAH. The patients with MMRd receiving fertility-preserving treatment achieved outcomes similar to those of the patients with NSMP. The molecular profiles might guide fertility-preserving treatment in the prognosis and clinical decisions.

Hypertensive disorders of pregnancy and severe acute respiratory syndrome coronavirus-2 infection.

OBJECTIVES: We aimed to determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with an increased risk of hypertensive disorders of pregnancy (HDP). METHODS: A multicenter retrospective cohort study of all pregnant patients who had SARS-CoV-2 testing and delivered in a large health system between March 2020 and March 2021. Cases were stratified into two groups: patients who tested positive for SARS-CoV-2 during pregnancy vs. patients who tested negative. The primary outcome of HDP, defined as a composite of gestational hypertension, preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP Syndrome), and eclampsia by standard criteria, was compared between the two groups. Statistical analysis included multivariable logistic regression to adjust for potential confounders such as maternal demographics and comorbidities. Patient ZIP codes were linked to neighborhood-level data from the US Census Bureau's American Community Survey. RESULTS: Of the 22,438 patients included, 1,653 (7.4%) tested positive for SARS-CoV-2 infection. Baseline demographics such as age, body mass index, race, ethnicity, insurance type, neighborhood-built environmental and socioeconomic status, nulliparity, and pregestational diabetes differed significantly between the two groups. SARS-CoV- 2 infection in pregnancy was not associated with an increased risk of HDP compared to those without infection (14.9 vs. 14.8%; aOR 1.06 95% CI 0.90-1.24). CONCLUSIONS: In this large cohort that included a universally-tested population with several socioeconomic indicators, SARS-CoV-2 infection in pregnancy was not associated with an increased risk of HDP.

Comparison of the effect of oral megestrol acetate with or without levonorgestrel-intrauterine system on fertility-preserving treatment in patients with early-stage endometrial cancer: a prospective, open-label, randomized controlled phase II trial (ClinicalTrials.gov NCT03241914).

OBJECTIVE: To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) plus oral megestrol acetate (MA) as fertility-preserving treatment in patients with early-stage endometrial cancer (EEC). METHODS: In this single-center, phase II study with open-label, randomized and controlled design, young patients (18-45 years) diagnosed with primary EEC were screened, who strongly required fertility-preserving treatment. Patients were randomly assigned (1:1) into MA group (160 mg oral daily) or MA (160 mg oral daily) plus LNG-IUS group. Pathologic evaluation on endometrium retrieved by hysteroscopy was performed every 3 months. The primary endpoint was complete response (CR) rate within 16 weeks of treatment. The secondary endpoints were CR rate within 32 weeks of treatment, adverse events, recurrent and pregnancy rate. RESULTS: Between July 2017 and June 2020, 63 patients were enrolled and randomly assigned. Totally 56 patients (26 in MA group; 28 in MA + LNG-IUS group) were included into primary-endpoint analyses. The median follow-up was 31.6 months (range, 3.1-94.0). No significant difference in 16-week CR rate were found between MA and MA + LNG-IUS groups (19.2% vs. 25.0%, p=0.610; odds ratio=1.40; 95% confidence interval=0.38-5.12), while the 32-week CR rates were also similar (57.1% and 61.5%, p=0.743), accordingly. More women in MA + LNG-IUS group experienced vaginal hemorrhage (46.4% vs. 16.1%; p=0.012) compared with MA group. No intergroup difference was found regarding recurrence or pregnancy rate. CONCLUSION: Compared with MA alone, the addition of LNG-IUS may not improve the early CR rate for EEC, and may produce more adverse events instead. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03241914.

Impacts of ovarian reserve on conservative treatment for endometrial cancer and atypical hyperplasia.

Objectives: Real-world data indicated that some endometrial atypical hyperplasia (EAH) and early endometrial carcinoma (EEC) patients of fertility preservation had a normal ovarian reserve, while some had a decreased ovarian reserve (DOR). This study was designed to investigate the effect of baseline ovarian reserve on the treatment of EAH and EEC patients who ask for preservation of fertility. Methods: This was a prospective cohort study conducted at a single university-affiliated fertility center. A total of 102 EAH and EEC patients who received fertility-preserving treatment between March 2019 and August 2020 were included and divided into a DOR group (n=22) and a non-DOR group (n=80). Results: The 32-week CR rate of the non-DOR group was significantly higher than that of the DOR group (60.3% vs. 33.3%, P =0.028). The DOR group had a longer treatment duration to achieve CR than the non-DOR group (40.07 vs. 29.71 weeks, P=0.008, HR: 0.54, 95% CI: 0.36-0.86). Multivariate logistic regression analyses demonstrated that DOR (OR: 0.35, 95% CI: 0.13-0.99, P=0.049) and BMI ≥25 kg/m2 (OR: 0.40, 95% CI: 0.17-0.92, P=0.031) were negatively associated with 32-week CR. Conclusions: Decreased baseline ovarian reserve is negatively correlated with the efficacy of fertility-preserving treatment in EAH and EEC patients, as this group has a lower CR rate and a longer treatment duration to achieve CR than those without DOR.

Acceptance of coronavirus disease 2019 vaccination among postpartum women during delivery hospitalization.

OBJECTIVE: The immediate postpartum period, during delivery hospitalization, represents a unique opportunity to offer coronavirus disease 2019 (COVID-19) vaccination to those who did not previously receive it. In this study, we evaluated patient characteristics associated with acceptance of vaccination in this group. METHODS: This retrospective cohort study evaluated all unvaccinated patients who were offered postpartum COVID-19 vaccination during delivery hospitalization between May 2021 and September 2021 at seven hospitals within a large integrated health system in New York. During the study period, each hospitalized, unvaccinated obstetrical patient was offered the vaccine prior to discharge. Patients with positive SARS-CoV-2 PCR testing during hospitalization were excluded. Medical records were reviewed to obtain sociodemographic characteristics and to confirm administration of COVID-19 vaccination. Multiple logistic regression was performed to model the probability of receiving postpartum vaccination. RESULTS: A total of 8,281 unvaccinated postpartum patients were included for analysis and 412 (5%) received a COVID-19 vaccine before hospital discharge. Patients who received the vaccine were more likely to be older, have private insurance, decline to answer questions about religious affiliation, and deliver in the final two months of the study period. Likelihood of receiving postpartum vaccination was not affected by race-ethnicity, preferred language, marital status, parity, body mass index, or neighborhood socioeconomic conditions. Patients who declined vaccination were more likely to have positive SARS-CoV-2 antibody testing at delivery compared to those who received vaccination (49 vs. 29%; p < .001). CONCLUSION: Only 5% of unvaccinated postpartum patients received a COVID-19 vaccine before hospital discharge. It is concerning that patients with public health insurance were less likely to receive vaccination. This may be due to variation in vaccine counseling or other unmeasured factors. Despite the low acceptance rate in our study population, COVID-19 vaccination should be offered in a variety of clinical settings to maximize opportunities for administration.

Effects of Weight Status and Related Metabolic Disorders on Fertility-Sparing Treatment Outcomes in Endometrial Atypical Hyperplasia and Endometrial Cancer: A Retrospective Study.

BACKGROUND: Although obesity was an independent risk factor for fertility-sparing treatment in endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC), the roles of other weight statuses and related metabolism were unclear. This study aimed to investigate the body mass index (BMI) interval that produced optimal treatment efficacy and the effects of related metabolic disorders in EAH/EEC patients. METHODS: A total of 286 patients (including 209 EAH and 77 well-differentiated EEC) under progestin therapy were retrospectively analyzed. The cumulative complete response (CR) rate, relapse rate, and fertility outcomes were compared among different weight or metabolic statuses. RESULTS: Underweight and overweight/obese status significantly decreased the cumulative 16-week and 32-week CR rate (p = 0.004, p = 0.022, respectively). The highest 16-week CR rate was observed at a BMI of 21-22 kg/m2 in the overall population (p = 0.033). Obesity (HR 0.37, 95%CI 0.15-0.90, p = 0.029) and PCOS (HR 0.55, 95%CI 0.31-0.99, p = 0.047) were associated with lower 16-week CR rate. Hyperuricemia (HR 0.66, 95%CI 0.45-0.99, p = 0.043) was associated with lower 32-week CR rate. The 16-week and 32-week CR rate (p = 0.036, p = 0.008, respectively) were significantly lower in patients exhibiting both obesity and hyperuricemia. CONCLUSIONS: The optimal fertility-sparing treatment efficacy was observed at a BMI of 21-22 kg/m2 in EAH/EEC. Hyperuricemia was an independent risk factor for long-term treatment outcomes.

Histopathologic evaluation of dichorionic twin placentas in unassisted and in vitro fertilized pregnancies affected by preeclampsia.

OBJECTIVE: Pregnancies achieved with assisted reproductive technology have an increased risk of multiple gestations, preeclampsia, and placental morphologic abnormalities. Inflammatory processes affect dichorionic twin pregnancies disproportionately more than singleton gestations and have been associated with adverse pregnancy outcomes, such as fetal growth restriction and preeclampsia. Our objective is to investigate the placental morphology of dichorionic twin pregnancies complicated by preeclampsia conceived with in vitro fertilization (IVF) versus unassisted. METHODS: This is a retrospective analysis of placentas from dichorionic twin pregnancies affected by preeclampsia conceived with IVF versus without assistance from 2010 to 2016 at a tertiary care university hospital. Placental pathology findings were analyzed both independently and in aggregate stratified into composite outcome scores using a modified placental synoptic framework. Individual placental abnormalities were grouped into composite categories based on the site of origin: anatomic placental abnormalities; maternal vascular malperfusion; placental villous maldevelopment; fetal vascular malperfusion; chronic utero-placental separation; maternal-fetal interface disturbance; inflammation of infectious etiology; and inflammation of idiopathic etiology. Placental histopathological statistical analysis was performed using Fisher's exact test. Demographic variables and pregnancy outcomes were compared between groups using the Student's t test or Mann-Whitney U test, where appropriate. p < .05 defined statistical significance. RESULTS: Of 117 dichorionic twin pregnancies, 60 resulted from IVF (Group A) and 57 were conceived without assistance (Group B). Patients in Group A were older (36 [29-37] vs. 33 [32-38] respectively; p = .042) and less parous (18.3% vs. 38.6% percent parous in Group A and Group B, respectively p = .009) than Group B, respectively. No differences were found between groups regarding mode of delivery, gestational age at delivery, placental weight/birthweight, fetal growth restriction, and discordance of fetal growth. There were significantly more inflammatory changes of unknown etiology and composite inflammatory abnormalities in Group A versus Group B (26.7% vs. 10.5%, p = .02). The cumulative number of inflammatory abnormalities per patient had a significantly different distribution among groups (p = .005), and Composite Chronic Inflammation and Infection were found to be significantly more abundant in Group A versus Group B (p = .02). The distribution of placental composite anatomic placental abnormalities, maternal vascular malperfusion, placental villous maldevelopment, fetal vascular malperfusion, chronic utero-placental separation, or maternal-fetal interface disturbance was not statistically different between groups. The distribution of placental abnormalities was not different between groups for any individually analyzed pathological condition. Due to the relatively small sample size, adjustment for potential confounders was not performed. CONCLUSION: Dichorionic twin pregnancies affected by preeclampsia are associated with more placental inflammatory abnormalities if conceived with IVF versus unassisted. Further research is needed to ascertain the underlying mechanisms of these observed differences.

Effect of Lockdown Period of COVID-19 Pandemic on Maternal Weight Gain, Gestational Diabetes, and Newborn Birth Weight.

OBJECTIVE: This study aimed to determine whether the lockdown period of the initial novel coronavirus disease 2019 (COVID-19) surge in New York affected gestational weight gain (GWG), newborn birth weight (BW), and the frequency of gestational diabetes mellitus (GDM). Maternal and newborn outcomes during the first wave of the pandemic were compared with those during the same timeframe in the previous 2 years. STUDY DESIGN: Retrospective cross-sectional study of all live singleton term deliveries from April 1 to July 31 between 2018 and 2020 at seven hospitals within a large academic health system in New York. Patients were excluded for missing data on: BW, GWG, prepregnancy body mass index, and gestational age at delivery. We compared GWG, GDM, and BW during the pandemic period (April-July 2020) with the same months in 2018 and 2019 (prepandemic) to account for seasonality. Linear regression was used to model the continuous outcomes of GWG and BW. Logistic regression was used to model the binary outcome of GDM. RESULTS: A total of 20,548 patients were included in the study: 6,672 delivered during the pandemic period and 13,876 delivered during the prepandemic period. On regression analysis, after adjustment for study epoch and patient characteristics, the pandemic period was associated with lower GWG (ß = -0.46, 95% confidence interval [CI]: -0.87 to -0.05), more GDM (adjusted odds ratio [aOR] = 1.24, 95% CI: 1.10-1.39), and no change in newborn BW (ß = 0.03, 95% CI: -11.7 to 11.8) compared with the referent period. The largest increases in GDM between the two study epochs were noted in patients who identified as Hispanic (8.6 vs. 6.0%; p < 0.005) and multiracial/other (11.8 vs. 7.0%; p < 0.001). CONCLUSION: The lockdown period of the pandemic was associated with a decrease in GWG and increase in GDM. Not all groups were affected equally. Hispanic and multiracial patients experienced a larger percentage change in GDM compared with non-Hispanic white patients. KEY POINTS: · The COVID-19 lockdown was associated with decreased GWG and increased GDM.. · No change in newborn BW was seen during the lockdown.. · Overall, the lockdown did not have a large clinical effect on these pregnancy outcomes..

Nonadherence to treatment protocol for severe hypertension in pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy are one of the leading causes of maternal mortality and severe morbidity. The American College of Obstetricians and Gynecologists recommends treatment of persistent severe hypertension because this has been shown to improve overall outcomes. Treatment remains inconsistent and may be influenced by patient-level sociodemographic and clinical characteristics. OBJECTIVE: This study aimed to identify which factors are associated with nonadherence to an institutional protocol for the treatment of severe hypertension in pregnancy. STUDY DESIGN: Retrospective cohort study of patients who had persistent severe hypertension (≥2 systolic blood pressures ≥160 mm Hg and/or diastolic blood pressures >110 mm Hg between 15 and 60 minutes apart) during their delivery hospitalization in 3 hospitals within an integrated health system from February 1, 2018 to March 1, 2020. Adherence to an institutional protocol was defined as receiving antihypertensive medication within 1 hour of a second severe blood pressure measurement. Demographic information, medical comorbidities, and delivery hospitalization characteristics were compared between women who received treatment based on institutional protocol and those who did not. Patient zone improvement plan codes were linked to neighborhood-level data from the US Census Bureau's American Community Survey to extract socioeconomic characteristics. A multivariable logistic regression was performed to evaluate factors associated with delayed treatment while adjusting for potential confounders. RESULTS: Of the 996 patients included, 449 (45%) received treatment within 60 minutes and 547 (55%) did not. Having an elevated, nonsevere range blood pressure (adjusted odds ratio, 0.55; 95% confidence interval, 0.38-0.79) or a severe range blood pressure (adjusted odds ratio, 0.25; 95% confidence interval, 0.16-0.38) on admission, persistent severe hypertension ≥1 hour before or after delivery (adjusted odds ratio, 0.27; 95% confidence interval, 0.27-0.45), and chronic hypertension (adjusted odds ratio, 0.58; 95% confidence interval, 0.37-0.93) were associated with timely treatment. Hospital site (adjusted odds ratio, 1.97; 95% confidence interval, 1.18-3.28) and increasing gestational age (adjusted odds ratio, 1.14; 95% confidence interval, 1.07-1.21) were associated with nonadherence to treatment protocol. A subanalysis evaluating treatment in 344 (35%) patients who had a nonelevated blood pressure on admission showed that White race, persistent severe hypertension within 1 hour of delivery, increasing gestational age, body mass index, twin gestation, preferred language other than English or Spanish, and a higher neighborhood unemployment rate were associated with nonadherence to treatment protocol. CONCLUSION: Several factors were associated with nonadherence to an institutional protocol for treatment of persistent severe hypertension. Provider bias may impact whether treatment is executed or not. Awareness of these risk factors may improve timely administration of antihypertensive medication in pregnant and postpartum patients.

Obstetrical Outcomes After Implementation of Laborist Model During the COVID-19 Pandemic.

OBJECTIVE: The COVID-19 pandemic prompted labor and delivery units to establish ways to decrease viral exposure to healthcare workers while continuing to deliver optimal patient care. A laborist model was implemented to improve safety at our tertiary care hospital in Long Island. The aim of the study is to determine whether implementation of a laborist model during the COVID-19 pandemic is associated with a change in the frequency of cesarean birth. METHODS: The retrospective cohort study included patients who delivered at a single tertiary center during March 2019 to May 2019 and March 2020 to May 2020 when our laborist model was initiated. The primary outcome compared the frequency of a cesarean delivery between both models. Secondary outcomes were the frequency of adverse obstetrical complications, which included intensive care unit admission, shoulder dystocia, intra-amniotic infection, hemorrhage, and need for blood transfusion. Statistical analysis included multivariable regression to adjust for potential confounders. RESULTS: A total of 1506 patients were included. Baseline characteristics were similar between the 2 groups. After adjusting for potential confounders, there was no significant difference in the frequency of cesarean births between both models (37% versus 35%; adjusted odds ratio, 1.003; 95% confidence interval, 0.46-2.89). Similarly, there were no significant differences in adverse outcomes between the study populations (adjusted odds ratio, 1.064; 95% confidence interval, 0.68-1.59). CONCLUSIONS: A change in practice behavior during a pandemic was not associated with an increase in frequency of cesarean births or adverse obstetrical outcomes.

An Ultra-Energy-Efficient and High Accuracy ECG Classification Processor With SNN Inference Assisted by On-Chip ANN Learning.

The ECG classification processor is a key component in wearable intelligent ECG monitoring devices which monitor the ECG signals in real time and detect the abnormality automatically. The state-of-the-art ECG classification processors for wearable intelligent ECG monitoring devices are faced with two challenges, including ultra-low energy consumption demand and high classification accuracy demand against patient-to-patient variability. To address the above two challenges, in this work, an ultra-energy-efficient ECG classification processor with high classification accuracy is proposed. Several design techniques have been proposed, including a reconfigurable SNN/ANN inference architecture for reducing energy consumption while maintaining classification accuracy, a reconfigurable on-chip learning architecture for improving the classification accuracy against patent-to-patient variability, and a dual-purpose binary encoding scheme of ECG heartbeats for further reducing the energy consumption. Fabricated with a 28nm CMOS technology, the proposed design consumes extremely low classification energy (0.3µJ) while achieving high classification accuracy (97.36%) against patient-to-patient variability, outperforming several state-of-the-art designs.

Severe maternal morbidity in pregnant patients with SARS-CoV-2 infection.

BACKGROUND: Although the increased risk for severe illness and adverse pregnancy outcomes associated with SARS-CoV-2 infection during pregnancy is well described, the association of infection with severe maternal morbidity has not been well characterized. OBJECTIVE: This study aimed to evaluate the risk for severe maternal morbidity associated with SARS-CoV-2 infection during pregnancy. STUDY DESIGN: This was a multicenter retrospective cohort study of all pregnant patients who had a SARS-CoV-2 test done and who delivered in a New York health system between March 1, 2020 and March 1, 2021. Patients with missing test results were excluded. The primary outcome of severe maternal morbidity, derived from the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine example list of diagnoses and complications, was compared between the following 2 groups: patients who tested positive for SARS-CoV-2 during pregnancy and patients who tested negative. Secondary outcomes included subgroups of severe maternal morbidity. Multivariable logistic regression was used to adjust for potential confounders such as maternal demographics, neighborhood socioeconomic status, hospital location, and pregnancy-related complications. A subanalysis was performed to determine if the risk for severe obstetrical hemorrhage and hypertension-associated or neurologic morbidity differed based on the timing of SARS-CoV-2 infection between those who tested positive for SARS-CoV-2 at their delivery hospitalization (ie, active infection) and those who tested positive during pregnancy but negative at their delivery hospitalization (ie, resolved infection). RESULTS: Of the 22,483 patients included, 1653 (7.4%) tested positive for SARS-CoV-2 infection. Patients with SARS-CoV-2 infection were more commonly Black, multiracial, Hispanic, non-English speaking, used Medicaid insurance, were multiparous, and from neighborhoods with a lower socioeconomic status. Patients with SARS-CoV-2 infection were at an increased risk for severe maternal morbidity when compared with those without infection (9.3 vs 6.5%; adjusted odds ratio, 1.52; 95% confidence interval, 1.21-1.88). Patients with SARS-CoV-2 infection were also at an increased risk for severe obstetrical hemorrhage (1.1% vs 0.5%; adjusted odds ratio, 1.78; 95% confidence interval, 1.04-2.88), pulmonary morbidity (2.0% vs 0.5%; adjusted odds ratio, 3.90; 95% confidence interval, 2.52-5.89), and intensive care unit admission (1.8% vs 0.5%; adjusted odds ratio, 3.29; 95% confidence interval, 2.09-5.04) when compared with those without infection. The risk for hypertension-associated or neurologic morbidity was similar between the 2 groups. The timing of SARS-CoV-2 infection (whether active or resolved at time of delivery) was not associated with the risk for severe obstetrical hemorrhage or hypertension-associated or neurologic morbidity when compared with those without infection. CONCLUSION: SARS-CoV-2 infection during pregnancy was associated with an increased risk for severe maternal morbidity, severe obstetrical hemorrhage, pulmonary morbidity, and intensive care unit admission. These data highlight the need for obstetrical unit preparedness in caring for patients with SARS-CoV-2 infection, continued public health efforts aimed at minimizing the risk for infection, and support in including this select population in investigational therapy and vaccine trials.

NrCAM secreted by endometrial stromal cells enhances the progestin sensitivity of endometrial cancer cells through epigenetic modulation of PRB.

Progestin is one of the main hormone treatment regimens for early-stage estrogen receptor- and progesterone receptor (PR)-positive endometrial cancer (EC). However, the response rate of EC to progestins is unsatisfactory. Investigating the mechanisms related to progestin treatment could help improve treatment efficacy. Studies have demonstrated that normal endometrial stromal cells (ESCs) increase the inhibitory effect of progestin on EC cell proliferation via paracrine signaling, but the mechanisms involved remain unclear. In this study, we found that ESCs had different morphological features between progestin-sensitive and -insensitive EC tissues. ESCs presented typical decidualization changes in progestin-sensitive cases, while they remained slim in progestin-insensitive EC lesions, indicating no response. Furthermore, ESCs enhanced the inhibitory effect of medroxyprogesterone acetate (MPA) on EC cell proliferation by secreting neuron cell adhesion molecule (NrCAM). MPA treatment enhanced NrCAM secretion by ESCs. EC xenografts in BALB/C nude mice demonstrated that MPA combined with NrCAM had an increased tumor inhibitory effect compared with MPA or NrCAM alone. Mechanistically, MPA upregulated NrCAM expression in ESCs through PR. Specifically, NrCAM increased PR expression in EC cells through TET1-induced hydroxymethylation of the PRB gene promoter region. These findings indicate that NrCAM or NrCAM combined with progestins could be a new EC treatment.

Clinical implications of morular metaplasia in fertility-preserving treatment for atypical endometrial hyperplasia and early endometrial carcinoma patients.

OBJECTIVE: Morular metaplasia (MM) is a benign epithelial metaplasia that sometimes appears in atypical endometrial hyperplasia (AEH) and endometrioid endometrial carcinoma (EEC). However, the clinical implications of MM for fertility-preserving treatment in AEH and EEC patients are unclear. This study investigated the clinical features and impact of MM on the efficacy of fertility-preserving treatment. METHODS: We retrospectively studied 427 AEH and EEC patients who received fertility-preserving treatment. Clinical features, treatment efficacy, and onco-fertility results were compared between patients with and without MM. RESULTS: MM appeared in 147 of 427 (34.4%) patients. Among them, 49 (33.3%) had MM only before treatment (BEF group), 32 (21.8%) had sustained MM before and during treatment (SUS group), and 66 (44.9%) had MM only during treatment (DUR group). The BEF group had a higher 12-month CR rate (98.0% vs 85.7%, p = 0.017) and shorter therapeutic duration to achieve CR (4.0 vs 5.7 months, p = 0.013) than the non-MM group had. In comparison with the non-MM group, the SUS and DUR groups had a lower CR rate after 7 months of treatment (SUS vs non-MM, 37.5% vs 61.1%, p = 0.010; DUR vs non-MM 33.3% vs. 61.1%, p < 0.001), and a longer median therapeutic duration to achieve CR (SUS vs non-MM, 7.6 vs. 4.0 months, p = 0.037; DUR vs non-MM, 7.9 vs. 4.0 months, p < 0.001). CONCLUSION: Appearance of MM only before treatment was positively correlated with outcome of fertility-preserving treatment, while sustained MM or appearance of MM only during treatment implied poorer outcome of fertility-preserving treatment in AEH and EEC patients.

Is minimally invasive surgery for clinical stage I uterine carcinosarcoma safe?

Minimally invasive surgery (MIS) has been a mainstay of the surgical management of uterine cancer since the mid-2000s. We aim to determine the role and safety of MIS in women with uterine carcinosarcoma (UCS). An Institutional Review Board-approved study identified all patients with UCS between January 2011 and December 2017 at our institution. Demographic and outcome measures were abstracted from the medical records and tumor registry. Cox proportional hazard models, log rank tests, and comparisons of means were used to calculate significance (p < 0.05). 129 women with UCS were identified during the study period. 62 cases (48%) were open procedures and 67 cases (52%) were MIS with the majority of the MIS group having robotic surgery. 55% of the patients had pathological stage 1 disease. Thirty-eight percent of UCS tumors were heterologous. 93% of patients received adjuvant therapy in the form of chemotherapy and/or radiation therapy. There was no difference in the recurrence-free survival (RFS) or overall survival (OS) between the open surgery and the MIS groups as well as between the heterologous and homologous UCS groups (p > 0.05). UCS represents a rare and aggressive subtype of endometrial cancer. Our data suggest that MIS is a safe surgical approach for staging in women with UCS.