Faculty Bibliography

OBJECTIVE:To obtain perspectives about existing compensation structures in gynecologic oncology, including common challenges and successful strategies within diverse systems. METHODS:Electronic mail was used to recruit OB/GYN department chairs and directors of cancer centers who were gynecologic oncologists and responsible for administering compensation structures at their institution. Using a semi-structured guide, three interviewers conducted 30-min qualitative interviews, which were recorded and transcribed. Two coders used the constant comparative method to summarize key themes. RESULTS:Response rate was 65 %, resulting in 17 interviewees. Participants were a third women and in their current position for a median of 7 years. The most prominent theme was the tension of balancing reimbursement for revenue-generating clinical activities with non-clinical work in research and education. Chair discretionary funds were useful to offset unfunded responsibilities. Broad clinical productivity measures were used: from more traditional work Relative Value Units (wRVUs) to measures that captured downstream impact, such as number of new patients or surgeries. Even in institutions with centralized funds flow systems, disparities were frequently noted for the monetary value assigned per wRVU. Academic scorecards were described as a method to ascribe value for academic work, often for bonus incentives. Another common stressor unique to gynecologic oncology was low reimbursement for chemotherapy-related services compared to surgery. Provision of regular productivity reports was common, but full transparency was controversial. CONCLUSIONS:Our inquiry demonstrates that our academic leaders are unable to use compensation to fully support areas they deem important.

A key treatment for patients with multiple myeloma is high-dose melphalan followed by autologous stem cell transplant (ASCT). It can provide a deep response with long-term remission. However, some patients progress quickly, and it is not clear why that is. Here, we performed single-cell RNA and T-cell receptor (TCR) sequencing of the immune microenvironment of 40 patients before and after ASCT to determine if differences in the immune composition could define those who would progress. Clear differences in cell populations were identified in progressors, including increased T-cell infiltration, decreased TCR diversity, and decreased frequency of monocytes and CD56bright NK cells. We identified cell interactions that predicted progression including increased frequency of CD8+ exhausted T cells and stromal cells and decreased frequency of CD56bright NK cells and plasmacytoid dendritic cells. We propose and validate a model of progression that can also be determined by flow cytometry. Together these data highlight the importance of the immune microenvironment in understanding responses to ASCT.

BACKGROUND:Routine collection and use of sexual orientation and gender identity data can assist in understanding and addressing the health disparities that affect lesbian, gay, bisexual, transgender, queer+ (LGBTQ+), also known as sexual and gender minority, individuals and communities. This study explored the implementation of a culturally relevant sexual and gender minority/sexual orientation and gender identity training program at a National Cancer Institute (NCI)-Designated Comprehensive Cancer Center. METHODS:The training consisted of 6 in-person 15-minute modules or 3 virtual 30-minute modules that occurred during established high-reliability organization huddles attended by oncology faculty and staff. Module topics were (1) Building LGBTQ+ Knowledge & LGBTQ+ Cancer Disparities, (2) Creating an Inclusive Environment, (3) Recovering From Misgendering/Making Assumptions, (4) How to Receive & Respond to Feedback, (5) Witnessing & Responding to Discrimination, and (6) Making and Sustaining a Change. All high-reliability organization attendees were considered eligible for participation and were provided with pretraining and post-training surveys. Survey items included comfort caring for sexual and gender minority patients, practice collecting sexual orientation and gender identity data, knowledge of sexual and gender minority health, and demographics. RESULTS:A total of 344 individuals completed the presurvey and 187 completed the postsurvey. Postsurvey results demonstrated a statistically significant improvement in self-perceived knowledge about sexual and gender minority health (scale: 0-100, with 100 = highest; presurvey vs postsurvey, 69 vs 84; P < .001). Respondents also reported statistically significant improvements in confidence in engaging with sexual orientation and gender identity questions (53 vs 79, P < .001) as well as intention to collect patient sexual orientation and gender identity information (49 vs 75, P < .001). Notably, sexual orientation and gender identity data collection tracking demonstrated a 311% increase in sexual orientation and 262% in gender identity disclosure during the study period. CONCLUSION/CONCLUSIONS:Despite the availability of sexual orientation and gender identity data fields within electronic health records, sexual orientation and gender identity disclosure remains an ongoing nationwide problem. Use of culturally relevant sexual and gender minority/sexual orientation and gender identity training can help improve oncology staff and clinician sexual and gender minority knowledge and confidence when engaging patients with and subsequent documentation of sexual orientation and gender identity data, resulting in improvement of data completion.

BACKGROUND:The prolonged turnaround time for next-generation sequencing (NGS) results may be a barrier to the timely selection of therapeutics in myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) with mutated TP53. Biomarker validation for early detection of TP53 mutation may have a significant impact on clinical decision-making. METHODS:In this study, p53 immunohistochemistry (IHC) (index test) and TP53 NGS (referent test) were performed on 145 bone marrow specimens from 82 unique patients with TP53-mutant MDS or AML to validate IHC as an early surrogate for NGS, and to assess the prognostic relevance of IHC. RESULTS:p53 IHC testing was able to correctly identify 95.5% of patients with TP53-mutant MDS and 100% of patients with TP53-mutant AML in this cohort. The mean p53 stain positivity was higher for AML compared to MDS (28% ± 3.67% vs. 8.8% ± 1.61%; p < .001), as well as for multihit TP53 compared to monoallelic TP53. Bootstrap analysis with 2000 iterations showed that a p53 IHC of 7% was the threshold best associated with multihit TP53. False-negative results were obtained with IHC in all TP53 sole nonsense or frameshift mutations. IHC positivity was inversely correlated with overall survival (OS), with the highest quintile of p53 positivity showing a median OS of just 2.53 months. CONCLUSIONS:IHC is a useful biomarker for the early detection of TP53-mutant MDS or AML and for prediction of TP53 allelic state. The results suggest a role for IHC across global markets, especially in geographic areas with inaccessibility to NGS testing.

INTRODUCTION/UNASSIGNED:Respiratory syncytial virus (RSV) causes significant morbidity and mortality in young children. For 25 years, palivizumab has been the only effective pharmaceutical RSV preventive. AREAS COVERED/UNASSIGNED:We summarize the development and a quarter-century of real-world evidence with palivizumab. We highlight its positive impact on the burden of RSV in high-risk children. Based on lessons learnt from its implementation, we suggest strategies for effective and equitable deployment of newer RSV preventives. EXPERT OPINION/UNASSIGNED:Following failure of the formalin-inactivated RSV vaccine in 1967, RSV intravenous immunoglobulin was approved in 1996 after three decades' research. Subsequently, palivizumab emerged as the most effective and safe RSV preventive, demonstrated by the IMpact trial, and was licensed in 1998 in the United States. Over the last 25 years, the benefits of palivizumab have been firmly established through a wealth of evidence, predominantly from high-income countries (HICs). To achieve a global impact with the newer RSV preventives, evidenced-based universal guidelines must be developed and endorsed by regulatory authorities and relevant scientific societies. Independent economic evaluations should incorporate all RSV-associated healthcare costs, reduction of long-term respiratory sequelae, and standardized outcomes. Most importantly, equity in product availability and implementation, particularly in low- and middle-income countries (LMICs) is essential.

OBJECTIVE:To compare anonymized and non-anonymized approaches for imputing race and ethnicity in descriptive studies of chronic disease burden using electronic health record (EHR)-based datasets. STUDY SETTING AND DESIGN/METHODS:In this New York City-based study, we first conducted simulation analyses under different missing data mechanisms to assess the performance of Bayesian Improved Surname Geocoding (BISG), single imputation using neighborhood majority information, random forest imputation, and multiple imputation with chained equations (MICE). Imputation performance was measured using sensitivity, precision, and overall accuracy; agreement with self-reported race and ethnicity was measured with Cohen's kappa (κ). We then applied these methods to impute race and ethnicity in two EHR-based data sources and compared chronic disease burden (95% CIs) by race and ethnicity across imputation approaches. DATA SOURCES AND ANALYTIC SAMPLE/UNASSIGNED:Our data sources included EHR data from NYU Langone Health and the INSIGHT Clinical Research Network from 3/6/2016 to 3/7/2020 extracted for a parent study on older adults in NYC with multiple chronic conditions. PRINCIPAL FINDINGS/RESULTS: = 0.33). When these methods were applied to the NYU and INSIGHT cohorts, however, racial and ethnic distributions and chronic disease burden were consistent across all imputation methods. Slight improvements in the precision of estimates were observed under all imputation approaches compared to a complete case analysis. CONCLUSIONS:BISG imputation may provide a more accurate racial and ethnic classification than single or multiple imputation using anonymized covariates, particularly if the missing data mechanism is MNAR. Descriptive studies of disease burden may not be sensitive to methods for imputing missing data.

BACKGROUND:Increased efforts to understand the reasons for the rise in pedestrian related traffic fatalities have demonstrated that these injuries occur in minority and lower income neighborhoods. The purpose of our study was to characterize the patient population suffering from pedestrian injuries in suburban setting, to determine whether the incidence of pedestrian injuries is associated with the social deprivation index (SDI) and to identify zip codes with a higher incidence of pedestrian injuries. METHODS:Single center, descriptive, retrospective cohort study of all patients suffering from pedestrian injuries admitted to our Level I Trauma Center (01/2014-10/2022). Demographic characteristics were summarized by groups and presented using the median (IQR) or frequency (%). Spearman's rank correlation was computed to assess the relationship between incidence of pedestrian injuries and SDI. ArcGIS was utilized to map the number of pedestrians injured, SDI, and percentage of households without a vehicle by zip code. RESULTS:719 patients identified had suffered pedestrian injuries. Median age of injury was 49(IQR 29-64), and median ISS was 8(IQR 4-14). There was a weak, but significant positive correlation between incidence of pedestrian injuries and SDI [r = .16; p-value = 0.02]. The zip code with the most injuries was Hempstead. CONCLUSIONS:Hempstead has the highest number of pedestrian injuries, highest SDI and highest percentage of households without a vehicle. However, overall correlation between incidence of pedestrian injuries and SDI was weak, suggesting that SDI may not be the only factor. Future research should focus on investigating other factors such as the presence of multilane arterial roads in these areas.

Separation of patients by insurance status in ambulatory care settings is a long-standing practice in academic medicine. This payer-based segregation of patients between resident and faculty outpatient practices may lead to inequitable quality of care. Informed by replies to a free-response text question for residents and program directors within the 2023 U.S. obstetrics and gynecology in-service examination, we provide commentary on this structural inequity within obstetrics and gynecology. The purpose of this commentary is to discuss the differences in patient population served, gaps in resources in resident clinics, quality of care and moral injury, limited continuity of care, and training and supervision. Further work is needed to guide systemic integration efforts and to explore the effects of program integration on patient health outcomes. We nonetheless urge academic medical centers to consider organizational shifts toward payer-integrated care.

OBJECTIVE:We examined if thyroid autoimmunity is relevant to the relationship between maternal TSH levels and pregnancy outcomes. DESIGN/METHODS:Retrospective cohort analysis of data from two randomized controlled trials (RCTs). SUBJECTS/METHODS:Participants of the Pregnancy in Polycystic Ovary Syndrome (PPCOS II, n = 746) and the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS, n = 832 with unexplained infertility) RCTs. EXPOSURE/METHODS:Pre-trial intervention levels of thyroid stimulating hormone (TSH) at threshold of ≥2.0 mU/L and thyroid peroxidase antibody (TPO-Ab) at titer threshold of ≥30 U/mL. MAIN OUTCOME/RESULTS:Live birth (primary outcome), pregnancy loss and preterm birth (secondary outcomes). Generalized linear model (GLM) analyses examined the relationship between exposure to TSH and TPO-Ab at specified thresholds with the specified outcomes; covariates adjusted for included age, body mass index, race, ethnicity, education, smoking, duration of infertility, PCOS (versus unexplained infertility) and randomized intervention arm in the respective RCTs. RESULTS:On adjusted analyses, live birth was significantly reduced in the exposed population (those with TSH ≥2.0 mU/L and TPO-Ab ≥30 U/mL, n= 117/1578, 7.4%, adjusted risk ratio [ARR] 0.55, 95% CI 0.35- 0.87) compared to the unexposed (those with TSH <2.0 mU/L and TPO-Ab <30 U/mL, n=865/1578, 54.8%). Furthermore, the risk of pregnancy loss and of early preterm birth (<32 weeks) was significantly higher in the exposed compared to the unexposed (ARR for pregnancy loss was 1.66, 95% CI 1.14- 2.42, and ARR for early preterm birth was 4. 82 (95% CI 1.53- 15.19). CONCLUSIONS:In women with TPO-Ab titers ≥30 U/mL, pregnancy outcomes may be compromised at TSH threshold of ≥2 mU/L. These findings of an interaction between TSH and TPO for pregnancy outcomes merit further investigation in prospective studies.

While the advent of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed or refractory DLBCL, it is unclear how survival has changed at the population level following its approval. Herein, we performed a population-based cohort study using the SEER-17 database. The primary exposure was a period of diagnosis (2014-2017 vs. 2018-2021), and these periods were selected based on the first FDA-approval of CAR-T in 2017. Study outcomes were relative survival (RS), overall survival (OS), lymphoma-specific survival (LSS), and the cumulative incidence of death from lymphoma (CIF). A total of 51,584 patients with DLBCL were included in the study with 24,861 patients diagnosed in time period-1 (2014-2017) and 26,723 patients diagnosed in time period-2 (2018-2021). The median age at diagnosis was 68 years (interquartile range, 57-77) and most patients were White (n = 42,190, 82%) with advanced stage at diagnosis (n = 28,203, 55%). In unadjusted analysis, the 5-year RS (95% CI) increased from 64% from 2014 to 2017 to 66% from 2018 to 2021, while 5-year OS increased from 54 to 55%, and 5-year LSS increased from 64 to 66%. On competing risks analysis, the 5-year probability of death from lymphoma decreased from 34 to 31%. The improvements in survival were observed across age, disease stage, and racial groups, and remained significant when adjusting for age, sex, race, stage, B symptoms and documented receipt of chemotherapy in multivariable survival models (adjusted OS HR = 0.97, 95%CI = 0.94-1.00, p = 0.04; adjusted LSS HR = 0.93, 95%CI = 0.90-0.96, p < 0.001). We found improved survival for patients with DLBCL diagnosed between 2018 and 2021 when compared to those diagnosed between 2014 and 2017. These findings will serve as the benchmark for future studies evaluating the impact of CAR-T administered earlier in their disease course.