Faculty Bibliography

In the United States, sexual, reproductive, and perinatal health inequities are well documented and known to be caused by a history of systemic oppression along many axes, including but not limited to race, ethnicity, gender, socioeconomic position, sexual orientation, and disability. Medical schools are responsible for educating students on systems of oppression and their impact on health. Reproductive justice advocates, including lay persons, medical students, and teaching faculty, have urged for integrating the reproductive justice framework into medical education and clinical practice. In response to medical student advocacy, we developed introductory didactic sessions on social and reproductive justice for preclinical medical students. These were created in a team-based learning format and include pre-course primer materials on reproductive justice. During the sessions, students engaged with hypothetical clinical vignettes in small groups to identify oppressive structures that may have contributed to the health outcomes described and potential avenues for contextually relevant and level-appropriate advocacy. The sessions took place in November 2019 (in-person) and 2020 (virtually) and were well attended by students. We highlight our experience, student feedback, and next steps, including further integration of reproductive health equity into medical school curricula in concert with department-wide education for faculty, residents, nursing, and allied health professionals. This introduction to social and reproductive justice can be adapted and scaled across different medical school curricula, enhancing the training of a new generation of physicians to become critically aware of how oppressive structures create health inequities and able to mitigate their impact through their roles as clinicians, researchers, and advocates.

Objectives: Patterns of disease recurrence on poly(ADP-ribose) polymerase inhibitor maintenance therapy are unclear and may affect subsequent treatment. This ad hoc subgroup analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 study evaluated patterns of initial recurrence in patients with advanced ovarian cancer (AOC). Methods: PRIMA included participants at high risk for disease progression. This ad hoc analysis only evaluated participants randomized to niraparib maintenance without evidence of disease at baseline. The number and site(s) of initial recurrent lesions at investigator-assessed progressive disease (PD) were evaluated. Results: Of the 314 niraparib-treated patients analyzed, 190 developed ≥1 new lesion (median number of new lesions, 1.0; interquartile range, 1"“2). In total, 93.2% (177/190) of patients developed 1"“3 lesions at first disease progression. The most common sites of recurrence were the peritoneum (30.0% [57/190]), lymph nodes (26.3% [50/190]), and liver (20.5% [39/190]). Similar results were observed when patients with PD were stratified by biomarker status, disease stage at diagnosis, and type of debulking surgery. Patients with homologous recombination-proficient tumors, stage III disease, or a history of primary debulking developed a median of 2.0 new lesions at first progression; patients with homologous recombination-deficient tumors, stage IV disease, or a history of interval debulking developed a median of 1.0 new lesion. Conclusions: Many patients with AOC without lesions at first-line maintenance treatment initiation develop oligometastatic disease at first recurrence. Prospective evaluation is required to determine whether these patients have improved outcomes when local therapies are combined with continuous, systemic, targeted maintenance therapy.

BACKGROUND:The relationship between fetal fraction and birth weight in twin gestations is poorly understood. OBJECTIVE:To investigate the relationship between first trimester cfDNA fetal fraction and birth weight < 10th percentile in twin gestations. STUDY DESIGN/METHODS:This is a planned secondary analysis of the Twin cfDNA Study, a 17-center retrospective cohort of twin pregnancies screened for aneuploidy using cfDNA in the first trimester from 12/2011 - 2/2022, excluding those with positive screen results for chromosomal aneuploidy. CfDNA testing was performed by a single lab using massively parallel sequencing (MPSS). Baseline characteristics and birth weight of pregnancies with normal fetal fraction were compared to those with low (<5%) and high (>95%) fetal fraction using univariable analyses and multivariable regression. RESULTS:A total of 1041 twin pregnancies were included. Chronic hypertension, elevated BMI, and self-identified Black race were associated with fetal fraction <5th percentile. There was no difference in median fetal fraction between those with birth weight <10th percentile in at least one twin (median [IQR] fetal fraction 12.2% [9.8, 14.8] versus those with normal birth weight (10th percentile) in both twins (median [IQR] fetal fraction 12.3% [9.7, 15.2] for normal birth weight, p = 0.49). There was no association between high or low fetal fraction and birth weight <10th percentile for one (p=0.45) or both (p=0.81) twins, and there was no association between high or low fetal fraction and birth weight <5th percentile for one (p=0.44) or both (p=0.74) twins. The results were unchanged after adjustment for potential confounders. CONCLUSION/CONCLUSIONS:In this large cohort, there was no association between the extremes of cfDNA fetal fraction and birthweight < 10th percentile, suggesting that first trimester fetal fraction may not predict impaired fetal growth in twin gestations.

Cisgender women and transgender men are less likely to be assessed for PrEP eligibility, prescribed PrEP, or retained in PrEP care. Thus, this pilot PrEP educational intervention was tailored for healthcare providers (HCPs) in obstetrics/gynecology who provide care to cisgender women and transgender men in an academically-affiliated, public hospital women's health clinic. The three-lecture educational curriculum designed for HCPs focused on PrEP eligibility and counseling, formulations and adherence, and prescription and payment assistance programs. Pre- and post-intervention surveys assessed HCP knowledge and barriers to PrEP counseling and prescription. Among n = 49 participants (mean age = 32.8 years; 85.7% cisgender women, mean years practicing = 4.2 years) pre-intervention, 8.7% had prior PrEP training and 61.2% felt very/somewhat uncomfortable prescribing PrEP. Post-intervention, knowledge of PrEP contraindications, eligibility, follow-up care, and assistance programs all increased. HCPs identified key barriers to PrEP care including lack of a dedicated PrEP navigator, culturally and linguistically appropriate patient materials on PrEP resources/costs, and PrEP-related content integrated into EHRs. Ongoing PrEP educational sessions can provide opportunities to practice PrEP counseling, including information on financial assistance. At the institutional level, incorporating PrEP screening in routine clinical practice via EMR prompts, facilitating PrEP medication monitoring, and enhancing telehealth for follow-up care could enhance PrEP prescription.

The vision of the International Menopause Society (IMS) is that all women across the world will have easy and equitable access to evidence-based knowledge and health care, empowering them to make fully informed midlife health choices. The aim of this White Paper is to provide a well-balanced educational narrative of the menopause and menopause hormone therapy (MHT) from IMS experts, leading into World Menopause Day 2024. This is achieved by exploring the anthropology and history of menopause, the principles and controversies of prescribing MHT, and by placing this into regulatory and menopause society contexts. The White Paper also lays the groundwork for the forthcoming updated IMS recommendations on menopause and will act as a blueprint for the future ethical management of menopause from practical and aspirational perspectives. An important section of the paper is 'The 5Ws of prescribing MHT': WHO is MHT for; WHAT types and doses of MHT; WHEN should MHT be started and stopped; WHY is MHT important; WHERE can MHT be accessed? A key points summary of this information is provided for healthcare professionals and the public. The summary provides 'easy to access' advice regarding several recent controversial MHT prescribing issues in the healthcare and media spotlights.

BACKGROUND:There is an increasing prevalence of durable mechanical circulatory supported patients in both the in-and-out of hospital communities. The scientific literature regarding the approach to patients supported by durable mechanical circulatory devices who suffer acutely impaired perfusion has not been well explored. METHODS:The International Liaison Committee on Resuscitation Advanced, Basic, and Pediatric Life Support Task Forces conducted a scoping review of the literature using a population, context, and concept framework. RESULTS:A total of 32 publications that included patients who were receiving durable mechanical circulatory support and required acute resuscitation were identified. Most of the identified studies were case reports or small case series. Of these, 11 (34.4%) included patients who received chest compressions. A number of studies reported upon delays in the application of chest compressions resulting from complexity due to the expected pulselessness in some patients with continuous flow left-ventricular assist devices as well as from concern regarding potential dislodgement of the mechanical circulatory support device. Three observational studies identified worse outcomes in durable mechanical circulatory support receiving patients with cardiac arrest and acutely impaired perfusion who received chest compressions as compared to those who did not, however those studies were at high risk of bias. Of 226 patients across 11 studies and two published scientific abstracts who sustained cardiac arrest while supported by durable MCS and underwent chest compressions, there were no reported instances of device dislodgement and 71 (31.4%) patients had favorable outcomes. CONCLUSIONS:There is a scarcity of evidence to inform the resuscitation of patients with durable mechanical circulatory support (MCS) experiencing acute impairment in perfusion and cardiac arrest. Reports indicate that delays in resuscitation often stem from rescuers' uncertainty about the safety of administering chest compressions. Notably, no instances of device dislodgement have been documented following chest compressions, suggesting that the risk of harm from timely CPR in these patients is minimal.

BACKGROUND:Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk. METHODS:We conducted a genome-wide interaction analysis of single nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than 3 drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies (GWAS). Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed effect meta-analyses were conducted. RESULTS:A potential novel region of association on 10p11.22, lead SNP rs7898449 (Pinteraction = 5.1 x 10-8 in the meta-analysis, Pinteraction = 2.1x10-9 in the case-control studies, Pinteraction = 0.91 cohort studies) was identified. A SNP correlated with this lead SNP is an eQTL for the NRP1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004). CONCLUSIONS:We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an eQTL for the NRP1, a protein that plays an important role in the development and progression of pancreatic cancer Impact: This work can provide insight into the etiology of pancreatic cancer particularly in heavy drinkers.

BACKGROUND:We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks. METHODS:IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. RESULTS:From 08/2016-03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months. CONCLUSIONS:The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC.

Lesbian, gay, bisexual, transgender, queer/questioning, or other sexual and/or gender expansive identities (LGBTQ+) in the United States are facing an insurmountable reintroduction of discriminatory and stigmatizing policies and legislation (i.e., Zombie Laws) particularly those pertaining to sexual practices, minoritized sexual orientations and gender identities, and access to equitable healthcare. This has a particularly devastating effect on cancer-related care and outcomes. Therefore, a call to action among researchers, policymakers, and activists is needed to protect LGBTQ + rights and ensure gains continue to ameliorate cancer-related health disparities.