Incidence and Risk Factors for a Malpositioned Intrauterine Device Detected on Three-Dimensional Ultrasound Within Eight Weeks of Placement.

OBJECTIVES: To estimate the incidence of intrauterine device (IUD) malpositioning detected on three-dimensional (3D) transvaginal ultrasound within 8 weeks of placement and identify risk factors for malpositioning. METHODS: Retrospective study of women who had an IUD placed at a large obstetrics and gynecology practice from January 1, 2015, to December 31, 2020. All patients underwent two-dimensional ultrasound at the time of insertion and routine three-dimensional ultrasound within 8 weeks. Baseline characteristics and potential risk factors were compared between women with correctly positioned and malpositioned IUDs. Odds ratios were calculated by logistic regression to identify risk factors independently associated with malpositioning. RESULTS: A total of 763 IUD placements were included, and 127 malpositioned IUDs were identified representing an overall rate of malpositioning of 16.6% (95% confidence interval [CI] 14.0-19.3) with 8.8% (95% CI 6.8-10.8) requiring removal. Patients with malpositioned IUD had higher rates of morbid obesity (13.4% versus 3.8%, adjusted odds ratio [aOR] 2.46, 95% CI 1.10-5.50), prior uterine window or rupture (9.0% versus 2.2%, aOR 2.78, 95% CI 1.06-7.30), copper IUD placement (64.2% versus 47.4%, aOR 1.99, 95% CI 1.31-3.03), and symptoms such as bleeding or pain at follow-up (35.8% versus 20.1%, aOR 2.58, 95% CI 1.67-3.98). Parity, breastfeeding, difficult insertion, and uterine size and positioning were not significant. CONCLUSIONS: The incidence of malpositioned IUD within 8 weeks of placement on 3D ultrasound is 16.6%, with 8.8% requiring removal. Significant risk factors for malpositioning include morbid obesity, prior uterine window or rupture, and copper IUD placement. These findings support the importance of routine follow-up 3D ultrasound after seemingly successful IUD placement.

A Medical Student Postpartum Telehealth Initiative During the COVID-19 Pandemic.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on our health systems and delivery of care and on the disruption of medical education. It has forced hospitals to move to a telehealth model for prenatal and postpartum visits and expedite discharges for postpartum patients in order to reduce exposure. We describe our medical school and hospital system initiative to employ medical student volunteers for postpartum telehealth calls during the peak of the COVID-19 pandemic in New York City. DESCRIPTION: Ten medical students conducted phone interviews with postpartum patients within 72 h of discharge at three hospitals in a large NYC health system, with faculty preceptors at each site who provided daily call assignments and oversight. Students called patients to screen for risk factors for postpartum complications, including preeclampsia and postpartum depression; provide additional contraception counseling; and address newborn care and health. One week and 2 week post-discharge calls were also made for COVID-19 positive patients for ongoing symptom monitoring and counseling. ASSESSMENT: We found numerous opportunities for intervention in postpartum health via telehealth, including addressing pharmacy-related needs, patient counseling, improving pain management, and identifying patients in need of emergent re-evaluation. CONCLUSION: As this pandemic continues to evolve, our model demonstrates the feasibility of telehealth and medical student involvement in postpartum care and its benefits to patients, medical student learning, and alleviation of burden on obstetric staff.

Arcuate Uterus as an Independent Risk Factor for Adverse Pregnancy Outcomes.

OBJECTIVE: The aim of the study is to estimate the association between arcuate uterus and pregnancy outcomes using controls selected from a similarly high-risk cohort. STUDY DESIGN: This is a retrospective cohort study of women with an arcuate uterus cared for by a single maternal-fetal medicine practice from 2005 to 2020. We included all women with a singleton pregnancy ≥20 weeks and diagnosis of arcuate uterus and randomly selected (3:1) patients with a singleton pregnancy and no uterine anomaly from the same practice as controls. Baseline characteristics and pregnancy outcomes were compared between the two groups. Chi-square, Fisher's exact, and independent samples t-test were used for data analysis, as indicated. RESULTS: A total of 37 women with an arcuate uterus (55 independent singleton pregnancies) and 165 controls were included. There were no differences in baseline characteristics. Women with an arcuate uterus had a significantly higher rate of spontaneous preterm birth less than 37 weeks (10.9 vs. 3.0%, p = 0.031) and were more likely to require vaginal progesterone (5.5 vs. 0.6%, p = 0.049) and administration of antenatal corticosteroids (16.4 vs. 5.5%, p = 0.020). Arcuate uterus was also associated with lower birthweight (3,028.1 ± 528.0 vs. 3257.2 ± 579.9 g, p = 0.010) and higher incidence of intrauterine fetal growth restriction (20.0 vs. 7.3%, p = 0.008), despite similar starting body mass index (BMI) and weight gain throughout pregnancy. There were no differences in preeclampsia, malpresentation, cesarean delivery, blood transfusion, retained placenta, or morbidly adherent placenta. CONCLUSION: Arcuate uterus is associated with a significantly increased risk of spontaneous preterm birth (<37 weeks), need for vaginal progesterone for short cervix and antenatal corticosteroids, fetal growth restriction, and lower mean birthweight. These findings suggest that arcuate uterus is not just a normal variant of uterine anatomy but rather a risk factor for poor fetal growth, short cervix, and a higher risk pregnancy. KEY POINTS: · Arcuate uterus is associated with increased risk of preterm birth and fetal growth restriction.. · Women with arcuate uteri had higher rates of vaginal progesterone use during pregnancy.. · Arcuate uterus should be treated as a true finding rather than a normal anatomical variant..

Evaluation of surgically excised breast tissue microstructure using wide-field optical coherence tomography.

BACKGROUND: Currently, positive margins at lumpectomy contribute to health care cost, patient anxiety, and treatment delay. Multiple technology solutions are being explored with the aim of lowering re-excision rates for breast-conserving surgery (BCS). We examined wide-field optical coherence tomography (WF-OCT), an innovative adjunct intraoperative imaging tool for tissue visualization of margins. METHODS: This IRB-approved pilot study included women with invasive or in situ carcinoma scheduled for primary BCS. Lumpectomy specimens and any final/revised margins were imaged by optical coherence tomography immediately prior to standard histological processing. The optical coherence tomography used provided two-dimensional, cross-sectional, real-time depth visualization of the margin widths around excised specimens. A volume of images was captured for 10 × 10 cm tissue surface at high resolution (sub-30 µm) to a depth of 2 mm. Integrated interpretation was performed incorporating final pathology linked with the optical image data for correlation. RESULTS: Wide-field optical coherence tomography was performed on 185 tissue samples (50 lumpectomy specimens and 135 additional margin shaves) in 50 subjects. Initial diagnosis was invasive ductal carcinoma (IDC) in 10, ductal carcinoma in situ (DCIS) in 14, IDC/DCIS in 22, invasive lobular carcinoma (ILC) in 2, ILC/DCIS in 1, and sarcoma in 1. Optical coherence tomography was concordant with final pathology in 178/185 tissue samples for overall accuracy of 86% and 96.2% (main specimen alone and main specimen + shave margins). Of seven samples that were discordant, 57% (4/7) were considered close (DCIS < 2 mm from margin) per final pathology. CONCLUSION: Wide-field optical coherence tomography demonstrated concordance with histology at tissue margins, supporting its potential for use as a real-time adjunct intraoperative imaging tool for margin assessment. Further studies are needed for comprehensive evaluation in the intraoperative setting.

Frequency of spontaneous resolution of vasa previa with advancing gestational age.

BACKGROUND: Vasa previa is a serious obstetric complication that can result in fetal hemorrhage and death on spontaneous labor. Suggested management for vasa previa is elective hospitalization and cesarean delivery before spontaneous labor. There is little reported evidence of the rate of vasa previa resolution over the course of gestation. Identification of the resolution rate and of factors predictive of resolution potentially could improve clinical management and patient counseling. OBJECTIVE: The purpose of this study was to identify the resolution rate of vasa previa across gestation and to determine clinical and sonographic factors that are associated with vasa previa resolution. STUDY DESIGN: We conducted a retrospective cohort study of all women who were diagnosed with vasa previa in a single ultrasound unit between 2005 and 2018. Vasa previa was defined as a fetal vessel within 2 cm of the internal cervical os on transvaginal sonography. The primary outcome was vasa previa resolution, defined as migration of the vasa previa to >2 cm away from the internal os. RESULTS: One hundred women with vasa previa that had been diagnosed at a mean gestational age of 22.8±4.9 weeks were included. Thirty-nine women (39.0%; 95% confidence interval, 30-49%) had resolution of vasa previa at a mean gestational age of 28.6-4.7 weeks. Factors that were associated with vasa previa resolution were an earlier gestational age at diagnosis (adjusted odds ratio, 6.10; 95% confidence interval,1.92-19.40), vasa previa did not cover the internal os at diagnosis (adjusted odds ratio, 8.29; 95% confidence interval, 2.79-24.62), and vasa previa was not the result of a resolved placenta previa (adjusted odds ratio, 2.85; 95% confidence interval, 1.01--8.03). One woman with a dichorionic twin pregnancy and vasa previa resolution (at 31 weeks gestation; fetal vessels located 2.8 cm from the internal os) presented at 33 weeks with massive bleeding and fetal death of twin A. It was unclear whether the death was related to vasa previa or placental abruption. CONCLUSION: Thirty-nine percent of vasa previas in our population resolved over the course of pregnancy. Earlier gestational age at diagnosis, vasa previa not covering the internal os, and not having a resolved placenta previa all are associated independently with an increased likelihood of vasa previa resolution. Women with vasa previa should be observed serially to assess for vasa previa resolution, because many will resolve in the third trimester.

Identification of a Folate Receptor-Targeted Near-Infrared Molecular Contrast Agent to Localize Pulmonary Adenocarcinomas.

Non-small cell lung cancer (NSCLC) is the number one cancer killer in the United States. Despite attempted curative surgical resection, nearly 40% of patients succumb to recurrent disease. High recurrence rates may be partially explained by data suggesting that 20% of NSCLC patients harbor synchronous disease that is missed during resection. In this report, we describe the use of a novel folate receptor-targeted near-infrared contrast agent (OTL38) to improve the intraoperative localization of NSCLC during pulmonary resection. Using optical phantoms, fluorescent imaging with OTL38 was associated with less autofluorescence and greater depth of detection compared to traditional optical contrast agents. Next, in in vitro and in vivo NSCLC models, OTL38 reliably localized NSCLC models in a folate receptor-dependent manner. Before testing intraoperative molecular imaging with OTL38 in humans, folate receptor-alpha expression was confirmed to be present in 86% of pulmonary adenocarcinomas upon histopathologic review of 100 human pulmonary resection specimens. Lastly, in a human feasibility study, intraoperative molecular imaging with OTL38 accurately identified 100% of pulmonary adenocarcinomas and allowed for identification of additional subcentimeter neoplastic processes in 30% of subjects. This technology may enhance the surgeon's ability to identify NSCLC during oncologic resection and potentially improve long-term outcomes.

Intraoperative Molecular Imaging Combined With Positron Emission Tomography Improves Surgical Management of Peripheral Malignant Pulmonary Nodules.

OBJECTIVE: To determine if intraoperative molecular imaging (IMI) can improve detection of malignant pulmonary nodules. BACKGROUND: 18-Fluorodeoxyglucose positron emission tomography (PET) is commonly utilized in preoperative assessment of patients with solid malignancies; however, false negatives and false positives remain major limitations. Using patients with pulmonary nodules as a study model, we hypothesized that IMI with a folate receptor targeted near-infrared contrast agent (OTL38) can improve malignant pulmonary nodule identification when combined with PET. METHODS: Fifty patients with pulmonary nodules with imaging features suspicious for malignancy underwent preoperative PET. Patients then received OTL38 before pulmonary resection. During resection, IMI was utilized to evaluate known pulmonary nodules and identify synchronous lesions. Tumor size, PET standardized uptake value, and IMI tumor-to-background ratios were compared for known and synchronous nodules via paired and unpaired t tests, when appropriate. Test characteristics of PET and IMI with OTL38 were compared. RESULTS: IMI identified 56 of 59 (94.9%) malignant pulmonary nodules identified by preoperative imaging. IMI located an additional 9 malignant lesions not identified preoperatively. Nodules only detected by IMI were smaller than nodules detected preoperatively (0.5 vs 2.4 cm; P < 0.01), but displayed similar fluorescence (tumor-to-background ratio 3.3 and 3.1; P = 0.50). Sensitivity of IMI and PET were 95.6% and 73.5% (P = 0.001), respectively; and positive predictive values were 94.2% and 89.3%, respectively (P > 0.05). Additionally, utilization of IMI clinically upstaged 6 (12%) subjects and improved management of 15 (30%) subjects. CONCLUSIONS: These data suggest that combining IMI with PET may provide superior oncologic outcomes for patients with resectable lung cancer.

A Case of Markedly Elevated Isolated Alkaline Phosphatase in the Third Trimester of Pregnancy.

Background: Alkaline phosphatase (ALP) is an enzyme produced by the liver, small intestine, bone, and kidneys as well as the placenta during pregnancy. ALP levels may increase up to twice the normal limit during pregnancy secondary to placental release and fetal bone growth. Rare case reports of extremely elevated levels of ALP during pregnancy have demonstrated possible association with adverse pregnancy outcomes. Case: The patient is a 36-year-old G2P1001 who was found to have extremely elevated ALP levels during pregnancy after presenting with bilateral lower leg swelling and rash after receiving the Pfizer COVID-19 vaccine. She subsequently developed intrahepatic cholestasis of pregnancy and preeclampsia. ALP peaked at 2,601 U/L immediately prior to delivery at 36 weeks 1 day. She was followed postpartum, and her ALP levels had nearly normalized by 15 weeks postpartum. Conclusion: Our case demonstrates a rare report of an extremely elevated level of ALP in the setting of multiple adverse pregnancy outcomes, including preterm delivery, preeclampsia without severe features, and intrahepatic cholestasis of pregnancy.

The association between high-normal blood pressure and the development of preeclampsia in twin pregnancies.

Objective: We sought to determine if women with twin pregnancies and blood pressure (BP) above the 95th percentile but within normal ranges (i.e. less than 140 systolic and 90 diastolic) are at increased risk of hypertensive disorders of pregnancy.Methods: Retrospective cohort study of all women with twin pregnancies being cared for by a single Maternal Fetal Medicine practice between 2012 and 2018. We identified all women who had a systolic blood pressure (SBP) or diastolic blood pressure (DBP) above the 95th percentile but less than 140 systolic and 90 diastolic at any point during pregnancy. Based on prior publications, the 95th percentile was defined as: a SBP 121-139 mmHg up to 30 weeks or 131-139 mmHg after 30 weeks, a DBP 81-89 mmHg up to 34 weeks or 85-89 mmHg after 34 weeks. We excluded women diagnosed with chronic hypertension either before or during pregnancy. The primary outcome was the development of preeclampsia. Chi-square and logistic regression were used.Results: A total of 457 patients met the inclusion criteria, of whom 109 (23.9%) had either a systolic or diastolic BP above the 95th percentile (but normal) at any time during pregnancy. These women were significantly more likely to develop preeclampsia (30.3 versus 12.6%, p < .001, aOR 2.32 (1.31, 4.09)) and gestational hypertension without preeclampsia (16.5 versus 4.6%, p < .001, aOR 4.27 (2.01, 9.07)).Conclusions: In women with twin pregnancies, a high-normal systolic or diastolic BP (above 120 systolic or 80 diastolic prior to 30 weeks, or above 130 systolic or 84 diastolic after 30 weeks) is associated with a significantly increased risk of gestational hypertension and preeclampsia.

Pregnancy outcomes in viable pregnancies with a septate uterus compared with viable pregnancies after hysteroscopic uterine septum resection.

BACKGROUND: Septate uterus is one of the more common Müllerian anomalies and is the anomaly most amenable to surgical correction. It is currently uncertain if hysteroscopic septum resection reduces the incidence of adverse pregnancy outcomes. OBJECTIVE: The purpose of this study was to compare pregnancy outcomes in women who had reached at least 20 weeks gestation with those women with a uterine septum and those women who had undergone septum resection before pregnancy. STUDY DESIGN: Retrospective cohort study of women with a history of uterine septum who were cared for by a large maternal-fetal medicine practice from 2005-2018. We included women with singleton pregnancies at >20 weeks gestation. Baseline characteristics and pregnancy outcomes were compared between women with a history of a hysteroscopic uterine septum resection and women with an unresected septum. Regression analysis was performed to control for differences in baseline characteristics. The analysis was repeated in nulliparous women only. RESULTS: A total of 109 women (163 pregnancies) were included. In the entire population, pregnancy outcomes did not differ between the groups, aside from a higher rate of cesarean delivery in the resected septum group. In the 63 nulliparous women, septum resection was associated with later gestational ages at delivery (39.1 vs 37 weeks; P=.030), decreased preterm birth <37 weeks gestation (4.5% vs 31.6%; adjusted odds ratio, 0.154; 95% confidence interval, 0.027-0.877), and an increased incidence of cesarean delivery in women who attempted vaginal delivery (30.6% vs 0%; P=.012). There was no difference in the rates of small for gestational age, preeclampsia, blood transfusion, retained placenta, or morbidly adherent placenta. CONCLUSION: In nulliparous women with viable pregnancies, hysteroscopic resection of a uterine septum is associated with a decreased incidence of preterm birth and an increased incidence of cesarean delivery. These findings need to be confirmed in a well-designed randomized trial before uterine septum resection is recommended routinely.

A Phase I Clinical Trial of Targeted Intraoperative Molecular Imaging for Pulmonary Adenocarcinomas.

BACKGROUND: Intraoperative identification of pulmonary nodules, particularly small lesions, can be challenging. We hypothesize that folate receptor-targeted intraoperative molecular imagining can be safe and improve localization of pulmonary nodules during resection. METHODS: Twenty subjects with biopsy-proven pulmonary adenocarcinomas were enrolled in a phase I clinical trial to test the safety and feasibility of OTL38, a novel folate receptor-α (FRα) targeted optical contrast agent. During resection, tumors were imaged in situ and ex vivo and fluorescence was quantified. Resected specimens were analyzed to confirm diagnosis, and immunohistochemistry was utilized to quantify FRα expression. A multivariate analysis using clinical and tumor data was performed to determine variables impacting tumor fluorescence. RESULTS: Of the 20 subjects, three grade I adverse events were observed: all transient nausea/abdominal pain. All symptoms resolved after completing the infusion. Sixteen of 20 subjects (80%) had tumors with in situ fluorescence with a mean tumor-to-background fluorescence level of 2.9 (interquartile range, 2.1 to 4.2). The remaining 4 subjects' tumors fluoresced ex vivo. In situ fluorescence was dependent on depth from the pleural surface. Four subcentimeter nodules not identified on preoperative imaging were detected with intraoperative imaging. CONCLUSIONS: This phase I trial provides preliminary evidence suggesting that folate receptor-targeted molecular imaging with OTL38 is safe, with tolerable grade I toxicity. These data also suggest that OTL38 accumulates in known lung cancers and may improve identification of synchronous malignancies. Our group is initiating a five-center, phase II study to better understand the clinical implications of intraoperative molecular imaging using OTL38.

An open label trial of folate receptor-targeted intraoperative molecular imaging to localize pulmonary squamous cell carcinomas.

BACKGROUND: Clinical applicability of folate receptor-targeted intraoperative molecular imaging (FR-IMI) has been established for surgically resectable pulmonary adenocarcinoma. A role for FR-IMI in other lung cancer histologies has not been studied. In this study, we evaluate feasibility of FR-IMI in patients undergoing pulmonary resection for squamous cell carcinomas (SCCs). METHODS: In a human clinical trial (NCT02602119), twelve subjects with pulmonary SCCs underwent FR-IMI with a near-infrared contrast agent that targets the folate receptor-α (FRα), OTL38. Near-infrared signal from tumors and benign lung was quantified to calculate tumor-to-background ratios (TBR). Folate receptor-alpha expression was characterized, and histopathologic correlative analyses were performed to evaluate patterns of OTL38 accumulation. An exploratory analysis was performed to determine patient and histopathologic variables that predict tumor fluorescence. RESULTS: 9 of 13 SCCs (in 9 of 12 of subjects) displayed intraoperative fluorescence upon NIR evaluation (median TBR, 3.9). OTL38 accumulated within SCCs in a FRα-dependent manner. FR-IMI was reliable in localizing nodules as small as 1.1 cm, and prevented conversion to thoracotomy for nodule localization in three subjects. Upon evaluation of patient and histopathologic variables, in situ fluorescence was associated with distance from the pleural surface, and was independent of alternative variables including tumor size and metabolic activity. CONCLUSIONS: This work demonstrates that FR-IMI is potentially feasible in 70% of SCC patients, and that molecular imaging can improve localization during minimally invasive pulmonary resection. These findings complement previous data demonstrating that ∼98% of pulmonary adenocarcinomas are localized during FR-IMI and suggest broad applicability for NSCLC patients undergoing resection.

Folate receptor-targeted molecular imaging improves identification of malignancy during pulmonary resection: a case report.

BACKGROUND: During minimally invasive pulmonary resection, both limited visualization and tactile feedback can make localization of pulmonary nodules and assessment for synchronous disease challenging. Intraoperative molecular imaging is an emerging technology that can enhance a surgeon's ability to detect cancers at the time of resection. CASE PRESENTATION: In this report, we describe the application of a folate receptor-targeted, near infrared optical contrast agent (OTL38) for the detection of an invasive pulmonary adenocarcinoma. During molecular imaging, an otherwise undetectable synchronous nodule was also identified. This finding resulted in intraoperative upstaging and operative plan modifications. CONCLUSION: This report marks the first successful utilization of a targeted, near infrared intraoperative molecular imaging probe useful for thoracic malignancies. This rapidly evolving technology may enhance the surgeon's ability to perform a number of oncologic procedures including tumor localization, margin assessment and intraoperative staging.