Faculty Bibliography

BACKGROUND:Mutations in DICER1 are uncommon, poorly understood, and infrequently found in thyroid nodules. METHODS:The objective of this study was to investigate category III/IV thyroid nodules according to The Bethesda System for Reporting Thyroid Cytopathology with DICER1 gene mutations detected in fine-needle aspiration cytology samples using ThyroSeq v3 molecular testing, with a focus on an exploration of the clinical and histopathologic outcomes of these nodules. In this multicenter study spanning more than 6 years, nodules were retrospectively analyzed for patient demographics, clinical course, cytologic features, and histopathology, where available. RESULTS:In total, 88 patients with somatic DICER1 mutations were included, with a mean age of 39.6 years and a female predominance. All mutations were in the somatic hotspot region, most commonly at the codon 5437 site. Most excised nodules showed benign histologic features (65.9%). Interestingly, the rate of malignancy was higher in this cohort compared with that in the national average. CONCLUSIONS:DICER1 mutations appear to confer a higher risk of malignancy, but are not associated with any specific cytological or histopathological distinguishing features.

BACKGROUND AND AIMS/OBJECTIVE:PredictSURE IBD is a prognostic blood test that classifies newly diagnosed, treatment-naïve Inflammatory Bowel Disease (IBD) patients into 'IBDhi' (high-risk) or 'IBDlo' (low-risk) groups (risk of future aggressive disease). We evaluated this assay in a multinational cohort and explored the effect of concomitant corticosteroids on its discrimination. METHODS:One hundred thirty-six (71 Ulcerative colitis [UC], 65 Crohn's Disease [CD]) and 41 (15 UC, 26 CD) patients with active IBD were 'unexposed' and 'exposed', respectively, to corticosteroids at baseline blood sampling. The number of treatment escalations, time to first escalation, and need for repeated escalations were compared between the biomarker subgroups. Another 20 patients (13 UC, 7 CD) were longitudinally sampled over 6 weeks after commencing corticosteroids. RESULTS:In corticosteroids-naïve UC and CD patients, all bowel surgeries (n = 6) and multiple therapy escalations (n = 10) occurred in IBDhi patients. IBDhi UC patients required significantly more treatment escalations, had a shorter time to first escalation, and a greater need for multiple escalations than IBDlo patients. No statistically significant differences were observed among CD patients. In corticosteroid-exposed patients, 66.6% of 'misclassifications' were IBDlo patients who required escalations. Among corticosteroid-treated patients with longitudinal sampling, 81.3% of those classified as IBDhi before steroids switched to IBDlo during therapy. CONCLUSIONS:No significant differences in treatment escalations were observed between biomarker-defined subgroups in CD. However, IBDhi UC patients required significantly earlier and more frequent therapy escalations, highlighting the need to further investigate PredictSURE IBD in UC. Notably, the discrimination ability of the biomarker was unreliable in patients receiving corticosteroid therapy.

PURPOSE/OBJECTIVE:Pelvic nodal irradiation is often used for high-risk prostate adenocarcinoma. A commonly used alternative to low dose rate (LDR) brachytherapy, a 3-fraction SBRT boost with fiducial tracking may allow for better coverage of extracapsular extension and macroscopic seminal vesicle invasion. This study evaluates the practical impact of prior pelvic nodal irradiation on fiducial tracking during a subsequent 3-fraction robotic stereotactic body radiation therapy (SBRT) boost for high-risk prostate cancer and compares these outcomes to a cohort of patients undergoing definitive 5-fraction SBRT. METHODS:In this institutional analysis, we prospectively collected fiducial tracking data for patients receiving a 3-fraction boost to the prostate and seminal vesicles after conventional nodal radiation. We also identified patients treated with 5-fraction SBRT with a low risk of nodal involvement. Monte Carlo estimates of the Fisher's Exact Test assessed fiducial tracking loss. Continuous variables within the 5- and 3-fraction cohorts were compared using the Mann-Whitney Test. Changes in fiducial tracking and their association with pre-treatment factors were analyzed through the Kruskal-Wallis test and Monte Carlo for tracking patterns, and Spearman Correlation Coefficient and Mann-Whitney Test for deviations in tracking over 5 fractions. RESULTS:A total of 405 patients were treated from April 2021 to September 2023 with: (1) 5-fraction SBRT (n = 309, 76%), and (2) 3-fraction boost after nodal irradiation (n = 96, 24%). There was no significant fiducial tracking loss over the three-fraction boost treatment regimen that proceeded nodal treatment (p = 0.63). However, there was a significant (p < 0.001) loss of fiducial tracking fidelity as demonstrated by progressive loss of one tracked fiducial over 5-fractions. There was significantly more volatility observed in the 5-fraction versus 3-fraction boost treatment (median volatility 2.4 vs. 0.0, p < 0.001). There were no significant associations between fiducial tracking, independently for 3- or 5-fractions, using either analysis method or volatility for ADT, time from fiducial placement to SBRT, CTV, and QOD vs. daily SBRT. CONCLUSIONS:Pelvic nodal treatment does not affect the quantity/quality of fiducial tracking in 3-fraction treatments. However, 5-fraction treatments showed a progressive loss and increased volatility in fiducial tracking over time. No pre-treatment factors significantly influenced fiducial tracking changes in either cohort, though ADT use trended towards increased volatility in the 5-fraction group. With a minimum of 4 fiducials placed for treatment, the loss/volatility of a single fiducial had no clinical impact on the tracking system.

OBJECTIVES/OBJECTIVE:This study examines the association between census tract-linked social vulnerability index (SVI) and maternal-fetal triage index (MFTI), a standardized score used to classify obstetric triage visit acuity. METHODS:This retrospective cohort study included patients at 20 weeks of gestational age or greater presenting to a New York City obstetric triage unit from March 2019 to April 2021, analyzing only the first pregnancy per patient. Exclusions included missing SVI or MFTI data and MFTI-5 (scheduled services). The primary exposure was SVI, and the primary outcome was MFTI score at the first triage visit. Multinomial logistic regression modeled the odds of MFTI-1 (stat) and MFTI-2 (urgent) visits relative to prompt/non-urgent visits, adjusting for potential confounders. RESULTS:Among 11,388 pregnant patients, most triage visits were classified as prompt or non-urgent (61.5 %), while 35.1 % were urgent, and 3.4 % were stat. Patients from neighborhoods with very high SVI had increased odds of an urgent visit (aOR 1.22, 95 % CI 1.06-1.41), as did those with chronic hypertension (aOR 1.46, 95 % CI 1.18-1.81), though SVI was not associated with stat visits. Stat visits were more likely during the COVID-19 pandemic (aOR 5.42, 95 % CI 4.04-7.28) and among patients with chronic hypertension (aOR 1.84, 95 % CI 1.15-2.94), while nulliparity and term presentation were associated with lower odds of a stat visit. CONCLUSIONS:Patients living in areas with a very high SVI score had increased odds of urgent triage visits but not stat visits. No racial or ethnic disparities were observed.

IMPORTANCE/UNASSIGNED:Repeating a prostate-specific antigen (PSA) test after an elevated measurement is a guideline-recommended component of the prebiopsy workup. However, it is unclear whether certain patients can be exempted from repeat PSA testing and proceed directly to further workup. OBJECTIVE/UNASSIGNED:To determine yearly PSA variability and implications of repeating an elevated PSA in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective multicenter cohort study used data from men aged 54 to 75 years participating in the screening arm of the randomized PLCO trial who received PSA testing annually over 6 years (between 1995 and 2006) without a prostate cancer diagnosis. Data were analyzed from February 10, 2023, to May 23, 2025. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was the proportion of PSA measurements above 1 of the 3 biopsy thresholds of interest (2.5, 3.0, and 4.0 ng/mL) that decreased below the threshold at the subsequent yearly measurement. Analyses were conducted at both the PSA test and patient levels. RESULTS/UNASSIGNED:Among 11 176 eligible patients (median age 60 years, IQR, 57-65 years), 2700 patients were included at a threshold of 2.5 ng/mL, 1928 patients at 3.0 ng/mL, and 952 patients at 4.0 ng/mL at least once. Among PSA measurements greater than or equal to 2.5 ng/mL, 22% (95% CI, 21%-23%) decreased below 2.5 ng/mL the following year; rates were similar for thresholds of 3.0 ng/mL and 4.0 ng/mL. At the patient level, 54% (95% CI, 53%-56%) of men with at least 1 PSA greater than or equal to 2.5 ng/mL had a subsequent level below this threshold, with slightly greater rates for the higher thresholds. A predictive scoring system incorporating current and prior PSA levels showed that patients with PSA levels persistently above thresholds had a low (<10%) probability of PSA decreasing below the threshold. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, significant intra-individual variability in PSA levels was observed in this large screening cohort, with many elevated values falling below the threshold at the next yearly measurement. These findings suggest the utility of guideline recommendations to confirm elevated PSA results in most patients before performing further diagnostic evaluation and that patients with a prior PSA score above a given biopsy threshold, and no recent PSA scores below that threshold, could proceed to further diagnostic evaluation without repeat testing.

The interaction between sleep, circadian rhythms and cardiovascular resilience is a crucial yet underexplored research area with important public health implications. Disruptions in sleep and circadian rhythms exacerbate hypertension, diabetes mellitus and obesity, conditions that are increasingly prevalent globally and increase the risk of cardiovascular disease. A National Heart, Lung, and Blood Institute workshop examined these connections, as well as the emerging concept of cardiovascular resilience as a dynamic and multifaceted concept spanning molecular, cellular and systemic levels across an individual's lifespan. The workshop emphasized the need to expand the focus from solely understanding whether and how sleep and circadian rhythm disturbances contribute to disease, to also exploring how healthy sleep and aligned circadian rhythms can increase cardiovascular resilience. To develop a Roadmap towards this goal, workshop participants identified key knowledge gaps and research opportunities, including the need to integrate biological, behavioural, environmental and societal factors in sleep and circadian health with cardiovascular research to identify therapeutic targets. Proposed interventions encompass behavioural therapies, chronotherapy, lifestyle changes, organizational policies and public health initiatives aimed at improving sleep and circadian health for better cardiovascular outcomes. Future cross-disciplinary research and translation of discoveries into public health strategies and clinical practices could improve cardiovascular resilience across the lifespan in all populations.

OBJECTIVE:To examine the rates of and reasons for presenteeism amongst obstetrics and gynecology (OBGYN) residents and program directors (PDs). METHODS:A national survey regarding presenteeism was administered to OBGYN residents and PDs. Sociodemographic data and residency program characteristics were collected from both groups. A Z test of independent proportions was used to investigate differences in reported presenteeism between residents and PDs. Bivariate analyses were performed to examine key outcomes of interest by sociodemographic and program characteristics. Kappa coefficients were calculated to assess agreement in program culture support for resident versus attending absence when unfit for duty. Multivariable linear regression analyses were performed to examine effects of hypothesized predictors of PD job satisfaction. RESULTS:A greater proportion of residents (51.3%) compared to PDs (21.2%) reported presenteeism (p < 0.001). The most common reasons reported by residents for presenteeism were concerns about forcing colleagues to cover (83.1%) and responsibility to care for patients (11.3%); while for PDs, they were responsibility to care for patients (35.6%) and residency administrative responsibilities (35.6%). In the resident survey, we found significant differences in rates of presenteeism by geographic region (p < 0.001), program type (p = 0.003), and training year (p = 0.001). We also found significant differences in program culture support for resident/attending/fellow leaves of absence when unfit for work by geographic region (p < 0.001). Lastly, we found significant differences in expectations for residents to "pay back" covered shifts during sick leave by geographic region (p < 0.001), and training year (p = 0.014). In the PD survey, we found significant differences in availability of emergency childcare by program size (p < 0.001) and program type (p = 0.003). We observed fair agreement between ratings of program culture support for resident versus attending absence when unfit for work (κ = 0.259, p <0.001). In adjusted analyses, we observed a negative effect of PD presenteeism (p = 0.044) and a positive effect of program culture support for attending absence (p = 0.007) on PD job satisfaction. CONCLUSIONS:Presenteeism was reported by a greater proportion of residents compared to PDs. A supportive culture for attending absence positively correlated with PD job satisfaction, whereas PD presenteeism had a detrimental effect. These findings suggest that institutional policies and support systems may have a critical impact on mitigating presenteeism and enhancing job satisfaction within residency programs, highlighting the need for targeted interventions to foster a supportive work environment for both residents and PDs.