Recent Research Publications- December 2023
Development of a coordinated registry network for pelvic organ prolapse technologies.
Baird CE, Chughtai B,, Kobashi K, Jung M, Sedrakyan A, Andrews S, Ferriter A, Cornelison T, Marinac-Dabic D.
BMJ Surg Interv Health Technol. 2022 Nov 11;4(Suppl 1):e000076. doi: 10.1136/bmjsit-2020-000076. PMID: 36393893; PMCID: PMC9660621.
Objectives: The accumulation of data through a prospective, multicenter Coordinated Registry Network (CRN) could be a robust and cost-effective way to gather real-world evidence on the performance of pelvic organ prolapse (POP) technologies for device-based and intervention-based studies. To develop the CRN, a group of POP experts consisting of representatives from professional societies, the Food and Drug Administration, academia, industry, and the patient community, was convened to discuss the role and feasibility of the CRN and to identify the core data elements important to assess POP technologies.
- A Delphi method approach was employed to achieve consensus on a core minimum dataset for the CRN. A series of surveys were sent to the panel and answered by each expert anonymously and individually. Results from the surveys were collected, collated, and analyzed by the study design team from Weill Cornell Medicine. Questions for the next round were based on the analysis process and discussed with group members via conference call. This process was repeated twice over a 6-month time period during which consensus was achieved.
Results: Twenty-one experts participated in the effort and proposed 120 data elements. Participation rates in the first and second round of the Delphi survey were 95.2% and 71.4%, respectively. The working group reached final consensus among responders on 90 data elements capturing relevant general medical and surgical history, procedure and discharge, short-term and long-term follow-up, device factors, and surgery and surgeon factors.
- The CRN successfully developed a set of core data elements to support the study of POP technologies through convening an expert panel on POP technologies and using the Delphi method. These standardized data elements have the potential to influence patient and provider decisions about treatments and include important outcomes related to efficacy and safety.
The American Urogynecologic Society Pelvic Floor Disorders Registry Bears Fruit.
Barber MD, Bradley CS.
Urogynecology (Hagerstown). 2022 Dec 1;28(12):797-799. doi: 10.1097/SPV.0000000000001290. PMID: 36409636.
Yurteri-Kaplan LA, Meyn L, Moalli PA, Foster RT Sr, Andy UU, Guaderrama N, Gutman RE, Anger JT, Hull A, Propst K, Shippey SS, Brown HW.
Urogynecology (Hagerstown). 2022 Dec 1;28(12):800-810. doi: 10.1097/SPV.0000000000001279. PMID: 36409637.
- There is a lack of high-quality long-term follow-up regarding pessary treatment. Most studies are case series or retrospective with a small sample size and short-term follow-up.
Objectives: This study aimed to evaluate differences in women who continue versus discontinue pessary use and the effectiveness, quality of life, and safety associated with pessary management at 1 year.
Study design: This study analyzed a multicenter national registry following women for 3 years with vaginal prolapse treated with a pessary or surgery. The primary outcome of this analysis was to compare the difference in characteristics among those who continue versus discontinue pessary use at 12 months.
- Among 1,153 participants enrolled, 376 (32.6%) opted for a pessary, and 296 (78.7%) were successfully fitted. Data were available for 240 participants (81%). At 1 year, 62% (n = 148) were still using pessaries, and 38% (n = 92) had stopped with 25% opting for surgery. Most commonly reported de novo adverse effects were urinary leakage (16%), feeling or seeing a bulge (12%), and vaginal discharge (11%). There was no difference in baseline characteristics among women who continued versus discontinued pessary use. At 12 months, subjective symptoms were similar between groups, with similar change in symptoms from baseline on most validated instruments. Those who continued to use a pessary reported worse urinary symptoms due to de novo urinary leakage ( P = 0.01).
- At 1 year, most women successfully fitted with a pessary continued pessary use. Although there was a significant improvement in condition-specific quality of life and low rates of complications, approximately 40% of women discontinued pessary use by 12 months. We were unable to identify any baseline characteristics associated with pessary discontinuation.
Effects of maternal hypertension on cord blood Arginine vasopressin receptor expression.
Gumusoglu S, Davis L, Schickling B, Devor E, Von Tersch L, Santillan M, Santillan D.
Pregnancy Hypertens. 2022 Nov 18;31:1-3. doi: 10.1016/j.preghy.2022.11.005. Epub ahead of print. Epub 2022 Nov 18. PMID: 36435036; PMCID: PMC9974773.
Arginine vasopressin (AVP) signaling is altered in preeclampsia and physiologic stress. AVP is implicated in fluid homeostasis and cardiovascular (CV) function, which is disrupted in some progeny from preeclamptic pregnancies. However, whether altered fetal AVP signaling occurs in preeclampsia is unknown. Here, we measured CV-related transcripts (e.g., AVP receptors) in cord blood via quantitative PCR. Chronic hypertension decreased AVPR1b, AVPR2, OXTR, LNPEP, and CUL5. AVPR1a, AVPR1b, and AVPR2 were decreased while OXTR was increased in preeclamptic cord blood. In sum, we found prenatal exposure to hypertension in pregnancy alters fetal AVP signaling and may thereby prime offspring CV disease risk.
Barber EL, Chen S, Pineda MJ, Robertson SE, Teoh D, Schilder J, O'Shea KL, Kocherginsky M, Zhang B, Matei D.
Cancer Res Commun. 2022 Oct;2(10):1293-1303. doi: 10.1158/2767-9764.crc-22-0147. Epub 2022 Oct 28. PMID: 36388466; PMCID: PMC9648489.
- The objective of this study was to assess the efficacy and safety of pembrolizumab in combination with standard carboplatin/paclitaxel in patients with advanced endometrial cancer (EC).
Patients and methods: This single-arm, open-label, multi-center phase II study enrolled patients with RECIST measurable advanced EC. Patients could have received < 1 prior platinum-based regimen and < one non-platinum chemotherapy. The primary endpoint was objective response rate (ORR). Planned sample size of 46 subjects provided 80% power to detect 15% ORR improvement compared to historical control rate of 50%.
Results: 46 patients were enrolled, and 43 were evaluable for ORR. Median age was 66 (range: 43-86). Thirty-four (73.9%) patients had recurrent and 12 (26.1%) primary metastatic EC. Patients received carboplatin AUC 6, paclitaxel 175mg/m2 and pembrolizumab 200mg IV every 3 weeks for up to 6 cycles. ORR was 74.4% (32/43), higher than historic controls (p = 0.001). Median PFS was 10.6 months (95% CI 8.3-13.9 months). The most common grade 1-2 treatment related adverse event (TRAEs) included anemia (56.5%), alopecia (47.8%), fatigue (47.8%) and neuropathy (13%), while the most common grade 3-4 TRAEs were lymphopenia, leukopenia, and anemia (19.6% each). High-dimensional spectral flow cytometry (CyTEK) identified enrichment in peripheral CD8+ and CD4+ T cell populations at baseline in responders. The CD8+ T cell compartment in responders exhibited greater expression levels of PD-1 and PD-L1 and higher abundance of effector memory CD8+ cells compared to non-responders.
- Addition of pembrolizumab to carboplatin and paclitaxel for advanced EC was tolerated and improved ORR compared to historical outcomes.
Patients in Iowa Counties Lacking Hospitals With Labor and Delivery Services Disproportionately Receive Care at Level III Maternal Care Hospitals When Undergoing Cesarean Delivery: A Retrospective Longitudinal Study.
Thenuwara KN, Dexter F, Ledolter J, , Epstein RH.
Cureus. 2022 Oct 25;14(10):e30683. doi: 10.7759/cureus.30683. PMID: 36439612; PMCID: PMC9691387.
- Many obstetrical patients from rural areas in the United States lack hospitals that provide labor and delivery care. Our objective was to examine the effects of such patients on caseloads of cesarean deliveries at Iowa hospitals with level III maternal care, as defined by the Iowa Department of Public Health (e.g., with obstetric anesthesiologists).
Methods: This retrospective longitudinal study included every discharge with cesarean delivery in the state of Iowa from October 2015 through June 2021. There were N=60,534 such deliveries from 76 hospitals, of which three were level III, and the rest were level I or II. Poisson regression models with robust variance estimation and controlling for geography, maternal risk factors, and insurance, were used to evaluate the binary outcome of whether patients received care at the university level III hospital in Eastern Iowa, or not. Similar models were also developed for care at the two private level III hospitals in Central Iowa, or not. Differences in the mean probabilities of receiving care at the level III hospitals were then estimated using logistic regression, with results reported in units of changes in cases per week at the hospitals.
Results: Statewide, the university level III hospital performed 7.4% of the cesarean deliveries, and the two private level III hospitals performed 23.4%. Patients from counties in which no cesarean deliveries were performed during the quarter of the year when they underwent a cesarean delivery disproportionately received care at level III hospitals versus levels I and II hospitals. Lower 99% confidence limits for incremental risk ratios were 1.46 and 4.20, respectively. Cesarean deliveries among patients residing in counties where no hospital had a labor and delivery ward were distributed unequally between the counties of the hospitals with level III maternal care. There were approximately 1.09 (standard error 0.10) extra cesarean deliveries per week at the university hospital versus 5.81 (standard error 0.11) at the private hospitals. The 1.09 vs 5.81 difference was caused, in part, by the effects of insurance and other hospitals with similar services.
- Patients residing in counties without labor and delivery care disproportionately go to level III hospitals. These results can help anesthesiologists, obstetricians, and analysts at hospitals with large tertiary (level III) programs interpret their annual increases in total obstetric anesthesia activity.
Rush CM, Blanchard Z, Polaski JT, Osborne KS, Osby K, Vahrenkamp JM, Yang CH, Lum DH, Hagan CR, Leslie KK, Pufall MA, , Gertz J.
Sci Rep. 2022 Nov 17;12(1):19731. doi: 10.1038/s41598-022-24211-8. PMID:
36396974; PMCID: PMC9672046.
Most endometrial cancers express the hormone receptor estrogen receptor alpha (ER) and are driven by excess estrogen signaling. However, evaluation of the estrogen response in endometrial cancer cells has been limited by the availability of hormonally responsive in vitro models, with one cell line, Ishikawa, being used in most studies. Here, we describe a novel, adherent endometrioid endometrial cancer (EEC) cell line model, HCI-EC-23. We show that HCI-EC-23 retains ER expression and that ER functionally responds to estrogen induction over a range of passages. We also demonstrate that this cell line retains paradoxical activation of ER by tamoxifen, which is also observed in Ishikawa and is consistent with clinical data. The mutational landscape shows that HCI-EC-23 is mutated at many of the commonly altered genes in EEC, has relatively few copy-number alterations, and is microsatellite instable high (MSI-high). In vitro proliferation of HCI-EC-23 is strongly reduced upon combination estrogen and progesterone treatment. HCI-EC-23 exhibits strong estrogen dependence for tumor growth in vivo and tumor size is reduced by combination estrogen and progesterone treatment. Molecular characterization of estrogen induction in HCI-EC-23 revealed hundreds of estrogen-responsive genes that significantly overlapped with those regulated in Ishikawa. Analysis of ER genome binding identified similar patterns in HCI-EC-23 and Ishikawa, although ER exhibited more bound sites in Ishikawa. This study demonstrates that HCI-EC-23 is an estrogen- and progesterone-responsive cell line model that can be used to study the hormonal aspects of endometrial cancer.