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December 2023

Recent Research Publications- December 2023

The International Society for the Study of Vulvovaginal Disease (ISSVD) Vulvar Awareness Day Campaign: Knowledge of Vulvovaginal Diseases Among Italian Obstetrics and Gynecology Residents.

Bevilacqua F, Selk A, Stockdale C, Vieira-Baptista P, Adedipe T, Bohl T, Marozio L, Borella F, Gallio N, Pollano B, Robba E, Barbierato I, Benedetto C, Preti M.

J Low Genit Tract Dis. 2023 Nov 8. doi: 10.1097/LGT.0000000000000777. Epub ahead of print. PMID: 37906606.

Objectives: The objective of this study is to investigate vulvovaginal disease (VVD) awareness in Italian obstetrics and gynecology (Ob/Gyn) residents.

Materials and methods: A 25-question survey on VVD basic knowledge (17 questions) and willingness to improve it (8 questions) was distributed through Ob/Gyn resident online group chats, from different Italian Universities in January 2023. A total number of 250 residents were invited to participate; 124 responses were obtained (response rate: 50%). Data were collected and analyzed using descriptive statistics through REDCap.

  • Overall, 87 of the 124 respondents (70%) fully completed the questionnaire and represented the study group. Residents were distributed among years of residency: 15% first year, 31% second year, 23% third year, 11% fourth year, and 20% fifth year. Most (60%) never attended a VVD clinic during residency, with an increasing percentage of attendance in later residency years (15% at first year vs 65% at fifth).Participants reported low knowledge of vulvar precancerous lesions and vulvoscopy but better knowledge of vaginitis, vulvar self-examination, and lichen sclerosus. Of the respondents, 50% were not satisfied with the education provided during residency, and more than 60% lacked confidence in managing VVD.All participants expressed a strong desire to improve their knowledge and skills, with 100% agreeing that every gynecologist should know the "basics" and 98% wanting to improve their knowledge through webinars (45%), lessons (34%), newsletters, and videos (19%).

Conclusion: Our findings indicate a significant need to improve VVD knowledge among Italian Ob/Gyn residents. Further efforts are necessary to provide information about VVD and comprehensive training programs in Italian Universities.

Believing women: a qualitative exploration of provider disbelief and pain dismissal among women with interstitial cystitis/bladder pain syndrome from the MAPP research network.

Brown VL, James A, Hunleth J, Bradley CS, Farrar JT, Gupta P, Lai HH, Lowder JL, Moldwin R, Rodriguez LV, Yang CC, Sutcliffe S.

Int Urogynecol J. 2023 Nov 22. doi: 10.1007/s00192-023-05677-0. Epub ahead of print. PMID: 37991567.

Introduction and hypothesis: Although allusions to the importance of a good physician-patient relationship are present throughout the interstitial cystitis/bladder pain syndrome (IC/BPS) literature, qualitative analysis of patients' perspectives on the clinical encounter is lacking, particularly among women who are most commonly affected by IC/BPS. Therefore, we adopted a patient-centered experiential approach to understanding female patients' perception of clinical encounters.

  • We re-analyzed previously collected data from a qualitative study on patient flare experiences including eight focus groups of female IC/BPS patients (n = 57, mean = 7/group). Qualitative analysis applied grounded theory to index all physician-patient interactions, then thematically coded these interactions to elucidate common experiences of clinical encounters.

Results: Women with IC/BPS shared common experiences of provider disbelief and pain dismissal. Discussions with participants demonstrated the extent to which these negative encounters shape patients' health care-seeking behavior, outlook, and psychosocial well-being. Appearing in more than one guise, provider disbelief and dismissal occurred as tacit insinuations, explicit statements, silence, oversimplification, and an unwillingness to listen and discuss alternative treatment. As a result, women adopted several strategies including: rotating specialists; "testing" physicians; self-advocacy; self-management; avoiding the stigma of chronic pain; crying; and opting for alternative medicine over biomedicine.

  • The prevalence of provider disbelief and pain dismissal among women with IC/BPS indicates a need to improve physician-patient communication, informed by the struggles, anxieties, and gendered inequities that female patients with chronic pain experience in their diagnostic journey. Results suggest that further investigation into the power dynamics of clinical encounters might be required.

In situ profiling reveals metabolic alterations in the tumor microenvironment of ovarian cancer after chemotherapy.

Corvigno S, Badal S, Spradlin ML, Keating M, Pereira I, Stur E, Bayraktar E, Foster KI, Bateman NW, Barakat W, Darcy KM, Conrads TP, Maxwell GL, Lorenzi PL, Lutgendorf SK, Wen Y, Zhao L, Thaker PH, Goodheart MJ, Liu J, Fleming N, Lee S, Eberlin LS, Sood AK.

NPJ Precis Oncol. 2023 Nov 3;7(1):115. doi: 10.1038/s41698-023-00454-0. PMID: 37923835

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline hydroxylation of hypoxia-inducible factor alpha in the stromal regions. Metabolites more abundant in the epithelial regions of post-NACT PR tumors were involved in the metabolism of nucleotides, and metabolites more abundant in the stromal regions of post-NACT PR tumors were related to aspartate and asparagine metabolism, phenylalanine and tyrosine metabolism, nucleotide biosynthesis, and the urea cycle. A predictive model built on ions with differential abundances allowed the classification of patients' tumor responses as ER or PR with 75% accuracy (10-fold cross-validation ridge regression model). These findings offer new insights related to differential responses to chemotherapy and could lead to novel actionable targets.

Resection of an endocardial uterine sarcoma metastasis to the tricuspid valve apparatus with valve repair.

Arshava AE, Isaacson AL, Goodheart MJ, Bashir MA.

JTCVS Tech. 2023 Jul 10;21:109-112. doi: 10.1016/j.xjtc.2023.06.015. PMID: 37854803; PMCID: PMC10580036.

Delivery outcomes in the subsequent pregnancy following the conservative management of placenta accreta spectrum disorder: A systematic review and meta-analysis.

Javinani A, Qaderi S, Hessami K, Shainker SA, Shamshirsaz AA, Fox KA, Mustafa HJ, Subramaniam A, Khandelwal M, Sandlin AT, Duzyj CM, Lyell DJ, Zuckerwise LC, Newton JM, Kingdom JC, Harrison RK, Shrivastava VK, Greiner AL, Lotfin R, Genc MR, Atasi LK, Abdel-Razeq SS, Bennett KA, Carusi DA, Einerson BD, Gilner JB, Carver AR, Silver RM, Shamshirsaz AA.

Am J Obstet Gynecol. 2023 Oct 31:S0002-9378(23)00802-5. doi: 10.1016/j.ajog.2023.10.047. Epub ahead of print. PMID: 37918506.

  • Cesarean hysterectomy is generally presumed to decrease maternal morbidity and mortality secondary to placenta accreta spectrum disorder (PAS). Recently, uterine-sparing techniques have been introduced in conservative management of PAS to preserve fertility and potentially reduce surgical complications. However, despite often expressing the intention for future conception, few data are available regarding the subsequent pregnancy outcome after conservative management of PAS. Thus, we aimed to perform a systematic review and meta-analysis to assess the subsequent pregnancy outcomes following conservative management of PAS.

Data sources: PubMed, Scopus, and Web of Science databases were searched from inception to September 2022.

Study eligibility criteria: We included all studies, with the exception of case studies, that reported the first subsequent pregnancy outcomes in individuals with a previous history of PAS who underwent any type of conservative management.

Study appraisal and synthesis method: The R programming language with the "meta" package was used. The random effects model and inverse variance method were used to pool the proportion of pregnancy outcomes.

Results: We identified five studies involving 1,458 subjects that were eligible for quantitative synthesis. The type of conservative management included placenta left in situ (n=1), resection surgery (n=1), and not reported in three studies. The PAS recurrence rate in the subsequent pregnancy was 11.8% (95% CI: 1.1-60.3, I2 = 86.4%), and 1.9% (95% CI: 0.0-34.1, I2 = 82.4%) underwent Cesarean hysterectomy. Postpartum hemorrhage occurred in 10.3% (95% CI: 0.3-81.4, I2 = 96.7%). A composite adverse maternal outcome was reported in 22.7% of subjects (95% CI: 0.0-99.4, I2 = 56.3%).

Conclusion: Favorable pregnancy outcome is possible following successful conservation of the uterus in a PAS pregnancy. Approximately one out of four subsequent pregnancies following conservative management of PAS experienced significant adverse maternal outcomes. Given such high incidence of adverse outcomes and morbidity, patient and provider preparation is vital when managing this population.

Study Design and Protocol of the Multisite Pregnancy 24/7 Cohort Study.

Whitaker KM, Jones MA, Smith K, Catov J, Feghali M, Kline CE, Santillan M, Santillan D, Zimmerman B, Gibbs BB.

Am J Epidemiol. 2023 Nov 3:kwad208. doi: 10.1093/aje/kwad208. Epub ahead of print. PMID: 37939072.

  • Inequities in COVID-19 vaccine accessibility and reliable COVID-related information disproportionately affected marginalized racial and ethnic communities in the U.S. The Get Out the Vaccine (GOTVax) program, an innovative statewide government-funded COVID-19 vaccine canvassing program in California, aimed to reduce structural barriers to COVID-19 vaccination in high-risk communities with low vaccination rates. GOTVax consisted of a community-academic-government partnership with 34 local trusted community-based organizations' (CBOs) to conduct COVID-19 vaccine outreach, education, and vaccine registration. The purpose of this qualitative evaluation study was to explore the barriers and facilitators of using local CBOs to deploy a geographically, racially, and ethnically diverse state-wide COVID-19 vaccine outreach program.
  • Semi-structured online interviews were conducted with participating GOTVax CBO leaders from November 2021 to January 2022. Transcripts were analyzed using reflexive thematic analysis.

Results: Thirty-one of 34 CBOs participated (91% response rate). Identified themes encompassed both facilitators and barriers to program participation. Key facilitators included leveraging trust through recognized entities; promoting empathetic, tailored outreach; and flexibility of milestone-based CBO funding contracts for rapid program implementation. Barriers included navigating community sociopolitical, geographic, and cultural factors; managing canvassers' safety; desiring metrics for self-evaluation of outreach success; mitigating canvassing technology challenges; and concerns of program infrastructure initially limiting outreach. CBOs problem-solved barriers with academic and government partners.

Conclusions: Between May and December 2021, the GOTVax program reached over 2 million California residents and registered over 60,000 residents for COVID-19 vaccination. Public health campaigns may improve benefits from leveraging the expertise of community-trusted CBOs and universities by providing flexible infrastructure and funding, allowing CBOs to seamlessly tailor outreach most applicable to local minoritized communities.

Neonatal immune cells have heightened responses following in-utero exposure to chorioamnionitis or COVID-19.

Gilley A, Boly TJ, Paden A, Bermick J.

Pediatr Res. 2023 Nov 10. doi: 10.1038/s41390-023-02888-5. Epub ahead of print. PMID: 37949998.

  • Chorioamnionitis alters neonatal immune responses. Gestational COVID-19 infection is associated with adverse pregnancy outcomes, but its impact on neonatal immunity is unclear. We hypothesized that gestational COVID-19 exposure would result in exaggerated neonatal immune responses, similar to chorioamnionitis-exposed neonates.
  • Term umbilical cord blood mononuclear cells (CBMCs) were isolated from neonates exposed to chorioamnionitis, gestational COVID-19 or unexposed controls. CBMCs were cultured and stimulated with heat-killed Escherichia coli, Streptococcus agalactiae or Staphylococcus epidermidis. A multiplexed protein assay was used to measure cytokine levels in cell culture supernatants and flow cytometry was used to evaluate cellular-level cytokine expression.
  • Both chorioamnionitis-exposed and COVID-19 exposed CBMCs demonstrated upregulation of IL-1β and IL-6 compared to unexposed CBMCs, while only COVID-19 exposure resulted in IL-8 upregulation. There were no differences between chorioamnionitis-exposed and COVID-19 exposed CBMCs when these groups were directly compared. Flow cytometry demonstrated immune cell subset specific differences in cytokine expression between the exposure groups.
  • : The fetal/neonatal response to maternal inflammation differed based on immune cell subset and etiology of inflammation, but the global neonatal cytokine responses were similar between exposure groups. This suggests that targeting perinatal inflammation rather than the specific etiology may be a possible therapeutic approach.

Impact: Neonatal immune cells have similar pathogen-associated global cytokine responses, but different cell-level immune responses, following in-utero exposure to chorioamnionitis or COVID-19. This is the first study to directly compare immune responses between neonates exposed to chorioamnionitis and COVID-19. This suggests that the fetal/neonatal cellular response to perinatal inflammation differs based on the etiology and severity of maternal inflammation, but still results in a similar overall inflammatory profile regardless of the cause of perinatal inflammation.

Decision regret among couples experiencing infertility: a mixed methods longitudinal cohort study.

Cusatis R, Johnson C, Schoyer KD, Tsaih SW, Balza J, Sandlow J, Flynn KE.

Reprod Health. 2023 Nov 9;20(1):165. doi: 10.1186/s12978-023-01699-5. PMID: 37940984; PMCID: PMC10633954.

  • : Decisions for how to resolve infertility are complex and may lead to regret. We examined whether couples and individuals who sought a consultation from a reproductive specialist for infertility later expressed decisional regret about their family-building choices and whether regret was associated with parental role, family-building paths, or outcomes.

Methods: This longitudinal mixed methods study included women and their partners who completed a questionnaire prior to their initial consultation with a reproductive specialist and 6 years later. The six-year questionnaire included the Ottawa Decision Regret Scale referencing "the decisions you made about how to add a child to your family." A score of 25+ indicates moderate-to-severe regret. Additional items invited reflections on family-building decisions, treatments, and costs. A systematic content analysis assessed qualitative themes.

  • Forty-five couples and 34 individuals participated in the six-year questionnaire (76% retention rate), Half (n = 61) of participants expressed no regret, which was similar by role (median 0 for women and supporting partners, F = .08; p = .77). One in 5 women and 1 in 7 partners expressed moderate-to-severe regret. Women who did not pursue any treatment had significantly higher regret (median 15; F = 5.6, p < 0.01) compared to those who pursued IVF (median 0) or other treatments (median 0). Women who did not add a child to their family had significantly higher regret (median 35; F = 10.1, p < 0.001) than those who added a child through treatment (median 0), through fostering/adoption (median 0), or naturally (median 5). Among partners, regret scores were not associated with family-building paths or outcomes. More than one-quarter of participants wished they had spent less money trying to add a child to their family. Qualitative themes included gratitude for parenthood despite the burdensome process of family-building as well as dissatisfaction or regret about the process. Results should be confirmed in other settings to increase generalizability.
  • This longitudinal study provides new insight into the burden of infertility. For women seeking parenthood, any of the multiple paths to parenthood may prevent future decision regret. Greater psychosocial, financial, and decision support is needed to help patients and their partners navigate family-building with minimal regret.