Recent Research Publications- July 2023
Cotyledonoid dissecting leiomyoma in pregnancy: a case report
Samuel Choice, Mildrede Bonglack, , Audai Alrwashdeh,
Proc Obstet Gynecol. 2023;12(1): Article 6 [10 p.].
Cotyledonoid dissecting leiomyoma (CDL) is a rare variant of uterine leiomyoma characterized by intramural dissection within the uterine corpus and a distinctive gross appearance resembling the cotyledons of the placenta. Despite their alarming, sarcomatous appearance both macroscopically and radiographically, these tumors are typically associated with bland histologic findings. Approximately 70 cases of CDL have been described in the literature. This case represents the second described case of CDL in pregnancy, the first in which a pregnancy was carried to term. A 28-year-old primigravid was incidentally found to have a massive, exophytic growth of the uterus on ultrasound with concomitant 14-week intrauterine pregnancy. The pregnancy was monitored with serial growth ultrasounds. She was delivered at 37 weeks via Cesarean section. After being lost to follow-up, the patient presented 2.5 years later with worsening abdominal fullness and persistent uterine mass.
Changing the Name of the Subspecialty (Back) to Urogynecology and Reconstructive Pelvic Surgery.
Barber MD, , Wendel GD Jr.
Obstet Gynecol. 2023 Jul 1;142(1):4-5. doi: 10.1097/AOG.0000000000005251.
Changing the Name of the Subspecialty (Back) to Urogynecology and Reconstructive Pelvic Surgery.
Barber MD, , Wendel GD Jr.
Urogynecology (Phila). 2023 Jul 1;29(7):593-594. doi: 10.1097/SPV.0000000000001382. Epub 2023 Jun 22.
Schrepf AD, Mawla I, Naliboff BD, Gallop B, Moldwin RM, Tu F, Gupta P, Harte S, Krieger JN, Yang C, Rodriguez L, Williams D, Magnotta V, Ichesco E, Harris RE, Clemens Q, Mullins C, Kutch JJ.
Pain. 2023 Jun 6. doi: 10.1097/j.pain.0000000000002944. Epub ahead of print.
Pain with bladder filling remains an unexplained clinical presentation with limited treatment options. Here, we aim to establish the clinical significance of bladder filling pain using a standardized test and the associated neural signature. We studied individuals diagnosed with urologic chronic pelvic pain syndrome (UCPPS) recruited as part of the multidisciplinary approach to the study of chronic pelvic pain (MAPP) study. Patients with urologic chronic pelvic pain syndrome (N = 429) and pain-free controls (N = 72) underwent a test in which they consumed 350 mL of water and then reported pain across an hour-long period at baseline and 6 months. We used latent class trajectory models of these pain ratings to define UCPPS subtypes at both baseline and 6 months. Magnetic resonance imaging of the brain postconsumption was used to examine neurobiologic differences between the subtypes. Healthcare utilization and symptom flare-ups were assessed over the following 18 months. Two distinct UCPPS subtypes were identified, one showing substantial pain related to bladder filling and another with little to no pain throughout the test. These distinct subtypes were seen at both baseline and 6 month timepoints. The UCPPS subtype with bladder-filling pain (BFP+) had altered morphology and increased functional activity in brain areas involved in sensory and pain processing. Bladder-filling pain positive status predicted increased symptom flare-ups and healthcare utilization over the subsequent 18 months when controlling for symptom severity and a self-reported history of bladder-filling pain. These results both highlight the importance of assessing bladder filling pain in heterogeneous populations and demonstrate that persistent bladder-filling pain profoundly affects the brain.
Rowlands CE, Folberg AM, Beickman ZK, Leslie KK, Givens BE.
Small. 2023 Jun 13:e2300096. doi: 10.1002/smll.202300096. Epub ahead of print.
Endometrial cancer is the most common gynecological malignancy worldwide and unfortunately has a much higher mortality rate in Black women compared with White women. Many potential factors contribute to these mortality rates, including the underlying effects of systemic and interpersonal racism. Furthermore, other trends in medicine have potential links to these rates including participation in clinical trials, hormone therapy, and pre-existing health conditions. Addressing the high incidence and disparate mortality rates in endometrial cancer requires novel methods, such as nanoparticle-based therapeutics. These therapeutics have been growing in increasing prevalence in pre-clinical development and have far-reaching implications in cancer therapy. The rigor of pre-clinical studies is enhanced by the likeness of the model to the human body. In systems for 3D cell culture, for example, the extracellular matrix mimics the tumor more closely. The increasing emphasis on precision medicine can be applied to cancer using nanoparticle-based methods and applied to pre-clinical models by using patient-derived model data. This review highlights the intersections of nanomedicine, precision medicine, and racial disparities within endometrial cancer and provides insights into reducing health disparities using recent scientific advances on the nanoscale.
Gonzalez-Bosquet J, Weroha SJ, Bakkum-Gamez JN, Weaver AL, McGree ME, Dowdy SC, Famuyide AO, Kipp BR, Halling KC, Yadav S, Couch FJ, Podratz KC.
Front Oncol. 2023 May 23;13:1105504. doi: 10.3389/fonc.2023.1105504.
- To identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.
Methods: We searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of E2F1 and CCNA2 expression and sequence variations in POLE, PPP2R1A, or FBXW7 (ECPPF) to prognostically stratify MSI-H/NSMP ECs. Clinical outcomes were annotated after integrating ECPPF and sequence variations in homologous recombination (HR) genes.
Results: Data were available for 239 patients with EC, which included 58 MSI-H and 89 NSMP cases. ECPPF effectively stratified MSI-H/NSMP EC into distinct molecular groups with prognostic implications: molecular low risk (MLR), with low CCNA2 and E2F1 expression, and molecular high risk (MHR), with high CCNA2 and E2F1 expression and/or PPP2R1A and/or FBXW7 variants. The 3-year disease-free survival (DFS) rate was 43.8% in the MHR group with clinicopathologic low-risk indicators and 93.9% in the MLR group (P<.001). In the MHR group, wild-type HR genes were present in 28% of cases but in 81% of documented recurrences. The 3-year DFS rate in patients with MSI-H/NSMP EC with clinicopathologic high-risk indicators was significantly higher in the MLR (94.1%) and MHR/HR variant gene (88.9%) groups than in the MHR/HR wild-type gene group (50.3%, P<.001).
- ECPPF may resolve prognostic challenges for MSI-H/NSMP EC by identifying occult high-risk disease in EC with clinicopathologic low-risk indicators and therapeutic insensitivity in EC with clinicopathologic high-risk indicators.
Wang C, Block MS, Cunningham JM, Sherman ME, McCauley BM, Armasu SM, Vierkant RA, Traficante N; Australian Ovarian Cancer Study Group; Talhouk A, Ramus SJ, Pejovic N, Köbel M, Jorgensen BD, Garsed DW, Fereday S, Doherty JA, Ariyaratne D, Anglesio MS, Widschwendter M, Pejovic T, Bowtell DD, Winham SJ, Goode EL.
Cancer Epidemiol Biomarkers Prev. 2023 Apr 3;32(4):542-549. doi: 10.1158/1055-9965.EPI-22-0941. PMID: 36790339; PMCID: PMC10073286.
Background: Better understanding of prognostic factors in tubo-ovarian high-grade serous carcinoma (HGSC) is critical, as diagnosis confers an aggressive disease course. Variation in tumor DNA methylation shows promise predicting outcome, yet prior studies were largely platform-specific and unable to evaluate multiple molecular features.
- We analyzed genome-wide DNA methylation in 1,040 frozen HGSC, including 325 previously reported upon, seeking a multi-platform quantitative methylation signature that we evaluated in relation to clinical features, tumor characteristics, time to recurrence/death, extent of CD8+ tumor-infiltrating lymphocytes (TIL), gene expression molecular subtypes, and gene expression of the ATP-binding cassette transporter TAP1.
- : Methylation signature was associated with shorter time to recurrence, independent of clinical factors (N = 715 new set, hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.10-2.46; P = 0.015; N = 325 published set HR, 2.87; 95% CI, 2.17-3.81; P = 2.2 × 10-13) and remained prognostic after adjustment for gene expression molecular subtype and TAP1 expression (N = 599; HR, 2.22; 95% CI, 1.66-2.95; P = 4.1 × 10-8). Methylation signature was inversely related to CD8+ TIL levels (P = 2.4 × 10-7) and TAP1 expression (P = 0.0011) and was associated with gene expression molecular subtype (P = 5.9 × 10-4) in covariate-adjusted analysis.
- Multi-center analysis identified a novel quantitative tumor methylation signature of HGSC applicable to numerous commercially available platforms indicative of shorter time to recurrence/death, adjusting for other factors. Along with immune cell composition analysis, these results suggest a role for DNA methylation in the immunosuppressive microenvironment.
Impact: This work aids in identification of targetable epigenome processes and stratification of patients for whom tailored treatment may be most beneficial.
Health Disparities in Ovarian Cancer: Report From the Ovarian Cancer Evidence Review Conference.
Mei S, Chelmow D, Gecsi K, Barkley J, Barrows E, Brooks R, , Jeudy M, O'Hara JS, Burke W.
Obstet Gynecol. 2023 Jul 1;142(1):196-210. doi: 10.1097/AOG.0000000000005210. Epub 2023 Jun 7. PMID: 37348095; PMCID: PMC10278570.
Health disparity, defined by the Centers for Disease Control and Prevention (CDC) as "preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations," is seen across multiple diseases. We conducted an evidence review of health disparities and inequities and their mitigation strategies related to ovarian cancer as part of a CDC-sponsored project to develop educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. Our review found profound disparities in outcomes such as survival, treatment, and stage at diagnosis by factors such as race and ethnicity, insurance, socioeconomic status, and geographic location. We found little direct evidence on mitigation strategies. Studies support equivalent response to equivalent treatment between groups, suggesting that adherence to National Comprehensive Cancer Network guidelines can at least partially mitigate some of the differences.
Executive Summary of the Ovarian Cancer Evidence Review Conference.
Burke W, Barkley J, Barrows E, Brooks R, Gecsi K, , Jeudy M, Mei S, O'Hara JS, Chelmow D.
Obstet Gynecol. 2023 Jul 1;142(1):179-195. doi: 10.1097/AOG.0000000000005211. Epub 2023 Jun 7. PMID: 37348094; PMCID: PMC10278568.
The Centers for Disease Control and Prevention awarded funding to the American College of Obstetricians and Gynecologists to develop educational materials for clinicians on gynecologic cancers. The American College of Obstetricians and Gynecologists convened a panel of experts in evidence review from the Society for Academic Specialists in General Obstetrics and Gynecology and content experts from the Society of Gynecologic Oncology to review relevant literature, best practices, and existing practice guidelines as a first step toward developing evidence-based educational materials for women's health care clinicians about ovarian cancer. Panel members conducted structured literature reviews, which were then reviewed by other panel members and discussed at a virtual meeting of stakeholder professional and patient advocacy organizations in February 2022. This article is the executive summary of the relevant literature and existing recommendations to guide clinicians in the prevention, early diagnosis, and special considerations of ovarian cancer. Substantive knowledge gaps are noted and summarized to provide guidance for future research.
Man vs. nature: Who will choose the fittest sperm?
Singh P, Mancuso AC, Van Voorhis BJ.
Fertil Steril. 2023 Jun 10:S0015-0282(23)00598-8. doi: 10.1016/j.fertnstert.2023.06.010. Epub ahead of print. PMID: 37302781.
Singh P, Amaro D, Obi O, Kiran F, Hediger E, Toler TL, Dickson PI, Grange DK.
JIMD Rep. 2023 Apr 30;64(4):261-264. doi: 10.1002/jmd2.12365. PMID: 37404675; PMCID: PMC10315371.
Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive long chain fatty acid β-oxidation disorder with a variable clinical spectrum, ranging from an acute neonatal presentation with cardiac and hepatic failure to childhood or adult onset of symptoms with hepatomegaly or rhabdomyolysis provoked by illness or exertion. Neonatal cardiac arrest or sudden unexpected death can be the presenting phenotype in some patients, emphasizing the importance of early clinical suspicion and intervention. We report a patient who had a cardiac arrest and died at one day of age. Following her death, the newborn screen reported biochemical evidence of VLCAD deficiency, which was confirmed with pathologic findings at autopsy and by molecular genetic testing.
Defining infertility: a qualitative interview study of patients and physicians.
Summers KM, Scherer A, Chasco EE, Ryan GL.
J Reprod Infant Psychol. 2023 Jun 8:1-15. doi: 10.1080/02646838.2023.2221277. Epub ahead of print. PMID: 37288784.
- To investigate if infertility patients and physicians apply a traditional biomedical model of disease in their conceptualisation of infertility, examine any contradictions and conflicts in conceptualisations, and examine areas of concordance and discordance between physicians and patients.
Methods: Semi-structured interviews were conducted with 20 infertility patients and 18 infertility physicians between September 2010 and April 2012. Interviews were analysed qualitatively to determine physician and patient conceptualisations of infertility, reactions to the definition of infertility as a disease, and potential benefits and concerns related to application of a disease label to the condition.
- Most physicians (n = 14/18) and a minority of patients (n = 6/20) were supportive of defining infertility as a disease. Many of the patients who agreed with classifying infertility as a disease expressed that they had not personally defined it as such previously. Physicians (n = 14) and patients (n = 13) described potential benefits of a disease label, including increases in research funding, insurance coverage, and social acceptability. Some patients (n = 10) described potential stigma as a negative consequence. When describing appraisals of infertility, both physicians (n = 7) and patients (n = 8) invoked religious/spiritual concepts. The potential for religious/spiritual appraisal to contribute to stigmatising or de-stigmatising infertility was discussed.
Conclusion: Our findings contradict the assumption that infertility physicians and patients are fully supportive of defining infertility as a disease. While potential benefits of the disease label were recognised by both groups, caution against potential for stigmatisation and unsolicited invocation of religion/spirituality suggest a more holistic model may be appropriate.
O'Connor E, Saylor L, O'Nan S, Schnettler W.
Obstet Gynecol Cases Rev. 2023;10(2):238. doi.org/10.23937/2377-9004/1410238
Left ventricular noncompaction cardiomyopathy (LVNC) is a rare form of familial cardiomyopathy attributed to failure of ventricular compaction during embryogenesis. Scant data exists regarding the management approach to pregnant patients with this condition. Additionally, few cases are reported in which both the mother and fetus are simultaneously affected by this condition during the antepartum period. This case is unique in that the patient carried a known genetic and echocardiographic diagnosis of LVNC, prior children born with confirmed LVNC by genetic and echocardiographic findings, and the current pregnancy affected by a perinatal diagnosis of LVNC via sonographicfindings.
Maxwell T, Wendt L, Castaneda C, Marsden K, Merrill AE, Swartz S, Steffen H, Johnson AL, Ten Eyck P, Rysavy MB, Jackson JB.
Gynecol Reprod Health. 2022; 6(1): 1-5. doi:10.33425/2639-9342.1174.
Objective: To determine if ABO blood group, age, body mass index (BMI), or symptomatic COVID-19 infection are associated with COVID-19 antibody response in unvaccinated COVID-19 antibody positive pregnant women at time of delivery.
- At the time of delivery, 2,499 consecutive pregnant women were tested for ABO blood group and antibodies to both the spike protein and nucleocapsid protein of the COVID-19 virus. The DiaSorin assay was used for antibody to spike protein analysis and the Roche assay for antibody to nucleocapsid protein. Gamma regression models with a log link were used to compare antibody signals, with blood group, age, and BMI as the predictors.
- 260 (10.4%) of 2,499 women who had not been vaccinated for COVID-19, were positive for both spike and nucleocapsid protein antibodies to COVID-19. The mean signal for COVID-19 nucleocapsid antibody was significantly lower for blood group AB (p=0.028) compared with blood group O. A relationship between blood group and presence of symptomatic COVID-19 was detected (p = 0.028), with asymptomatic individuals having blood group B at a higher rate than the symptomatic individuals do. No other significant pairwise differences between blood groups were detected. There was no significant difference in signal level of antibodies to COVID-19 spike protein between any of the blood groups. Mean signals for antibodies to spike and nucleocapsid proteins were significantly higher in older women (p=0.001 for spike protein antibody and p=0.002 for nucleocapsid antibody). Significantly higher signal levels of antibody to spike and nucleocapsid proteins were found in women with class 2/3 obesity (p=0.022 and p=0.003, respectively).
Conclusions: Pregnant women of AB blood group had lower antibody signal to nucleocapsid protein compared to the O blood group, and women of older age and greater BMI had higher antibody signal to COVID-19 spike and nucleocapsid proteins. There was a significant association between women with blood group B and asymptomatic infections.
Evaluation of Maternal Near Miss Events At Tibebe Ghion Specialized Hospital In Bahir Dar, Ethiopia.
De Haan JL, Rysavy MB, Misgan E, Manorot A, Wole B, Addis N, Wu C, Worku A.
Ethiopian Journal of Reproductive Health. 2023 Jan;15 (1):1-9.
- Maternal mortality and morbidity are significant challenges in Ethiopia. The maternal mortality ratio remains high with recent estimates of 412 maternal deaths per 100,000 live births as of 2016 in the nation. Maternal Near Miss events (MNM) are severe morbidities in which a woman narrowly escapes death. In order to develop ways to improve maternal mortality and morbidity, this study sought to estimate: 1) the prevalence of maternal mortality and MNM; and 2) the associated risk factors for these events, at a tertiary referral hospital in Bahir Dar, Ethiopia.
METHODS: This was a cross-sectional study of 658 consecutive delivering pregnant patients and their neonates at Tibebe Ghion Specialized Hospital (TGSH) in Bahir Dar, Ethiopia, from February 26-June 10, 2020. Demographic and outcome data were collected as part of a quality improvement initiative using the REDCap mobile app. Univariate and multivariate logistic regression were used to investigate the relationship between the key demographic and clinical variables with MNM. The creation of the database was approved by the TGSH clinical care committee in February 2020 and the University of Iowa Institutional Review Board approved the de-identified data analyses.
RESULTS: There were no maternal deaths and 70 MNM during the study period. The median patient age was 26 years (IQR 23-30); 49% of women were nulliparous, and 56% delivered vaginally. Patients had higher odds of experiencing MNM if living in a rural area (OR=3.71, p<0.01) or with a hypertensive disorder of pregnancy (OR=2.27, p=0.03). The postpartum hemorrhage rate was 1.7%.
- The MNM and mortality rates at TGSH were less than elsewhere in the region. Living in a rural area and having hypertensive disorders of pregnancy were major predictors of MNM events. Future quality improvement projects should be developed to increase antenatal care attendance, help rural women receive antenatal care, and improve treatment for hypertensive disorders in pregnancy.
Burns R, Ferari C, , Kovacevic N, Orzel J, Padmanabhan P, Peterson C, Powell C, Nakatsuka H, Vollstedt A, Walter B.
The Journal of Urology. 2023 Apr;209(Supplement 4):e514. doi: 10.1097/JU.0000000000003275.03.