Faculty Bibliography

PURPOSE/OBJECTIVE:EA1181 (ClinicalTrials.gov identifier: NCT04266249) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point-3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)-will be reported when data mature. METHODS:Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors associated with pCR. RESULTS:A total of 2,175 patients were enrolled (781 HER2+/estrogen receptor‑negative [ER-]; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER- and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER- tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables. CONCLUSION/CONCLUSIONS:Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER- and one third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.

INTRODUCTION/BACKGROUND:The American Urological Association (AUA) Annual Meeting is consistently competitive, accepting approximately one-third of the scientific abstracts submitted. Following abstract presentation, manuscript publication offers the opportunity to more widely disseminate research findings and methodology. Several prior studies have evaluated the publication rate of urology abstracts presented at regional and/or national conferences. In this study, we aim to both identify factors of Pediatric Urology abstracts presented at the annual meeting that were associated with an increased likelihood of manuscript publication and evaluate trends over time. METHODS:All Pediatric Urology abstracts presented at AUA annual meetings from 2013 to 2022 were reviewed. Data was collected on primary author degree type, presentation format (e.g. poster v. podium), and author geographic region. Manuscripts were searched for on PubMed and Google Scholar using the abstract titles and authors' names. Journal name, year of publication, and journal impact factor were recorded for published manuscripts. Impact factors were based on 2024 published values. SPSS statistical software was then used to analyze descriptive statistics and perform chi square analysis for categorical variables. Descriptive statistics, chi-square tests with pairwise Bonferroni correction, Cochran-Armitage trend testing, multivariable logistic regression, and Kaplan-Meier time-to-event analyses were performed. RESULTS:604 Pediatric Urology abstracts were presented from 2013 to 2022. Of these, 456 (75.5%) were moderated posters, 112 (18.5%) were videos, and 36 (6.0%) were podium presentations. 240 (39.7%) of these resulted in published manuscripts. Median time to publication was 1 years (IQR 1-2). 88.8% of published manuscripts (n = 213) had a physician listed as first author. Though there was an upward trend in the number of abstracts presented at annual meetings from 2013 (n = 72) to 2022 (n = 94), the rate of manuscript publication did not differ significantly across years (p = 0.066). An ordinal trend test, however, indicated a modest decline in publication rate across the study period (Cochran-Armitage p = 0.030). Manuscripts were published in 55 different journals with a median impact factor of 2.3 (IQR 1.9-6.8). 217 manuscripts (90.4%) were published within two years of abstract presentation. In contrast to several prior studies which found that podium presentations were more likely to subsequently get published as manuscripts, moderated poster presentations demonstrated the highest publication rate (44.7%), followed by podium presentations (30.6%), and video presentations (22.3%). Pairwise comparison with Bonferroni correction showed this format effect was driven by the difference between moderated poster and video presentations (adjusted p < 0.001); podium presentation were not statistically separable from either group.AUA geographic region was not associated with likelihood of manuscript publication (p = 0.648). CONCLUSIONS:The overall manuscript publication rate for Pediatric Urology abstracts at the AUA annual meeting over ten years was 39.7% (publication searches conducted through March 2026). Presentation format was significantly associated with publication likelihood; pairwise comparison showed this effect was driven by the difference between poster and video presentations, while podium presentations were not statistically separable form either group given the limited window in which podium was offered (2019 and 2022). With moderated poster presentations demonstrating the highest publication rate. Geographic region did not impact likelihood of publication. The annual conversion rate showed a modest decline across the study period (trend p = 0.030), which may partly reflect shorter publication follow-up for recent meeting years.

BACKGROUND/UNASSIGNED:It is unknown how the increased range of motion and improved gait mechanics provided by total ankle arthroplasty (TAA) affects the progression of subtalar arthritis compared with ankle arthrodesis (AA). We hypothesized that patients treated with TAA would have a lower incidence of postoperative subtalar arthrodesis (SA) compared to AA. METHODS/UNASSIGNED: <.05. RESULTS/UNASSIGNED: > .05). In a multivariate analysis, AA remained associated with increased risk of requiring SA (OR = 1.90, CI = 1.01-3.56). CONCLUSION/UNASSIGNED:In this study, we found a significantly higher incidence of subtalar arthrodesis following AA compared with TAA. Surgeons may consider the risk of progression to SA when deciding between TAA and AA for patients with advanced ankle arthritis, particularly in preoperative counseling for patients without existing subtalar arthritis, as TAA may offer an opportunity to mitigate this risk. LEVEL OF EVIDENCE/UNASSIGNED:Level III, retrospective comparative study.

BACKGROUND:People with multiple sclerosis (pwMS) treated with anti-CD20 monoclonal antibodies have an elevated infection risk, yet long-term comparative data with oral fumarates are limited. OBJECTIVE:To compare infection incidence, healthcare resource utilization, and relapse outcomes among pwMS receiving fumarate or anti-CD20 therapy for ⩾2 years. METHODS:This retrospective propensity-matched (1:2) analysis used US Komodo Health claims (1 January 2016-31 May 2022) for pwMS aged 18-64 years with ⩾2 years of continuous follow-up. Outcomes were assessed using Poisson generalized linear models. RESULTS: = 0.021). CONCLUSIONS:Fumarate therapy was associated with a lower infection risk versus anti-CD20s. The infection rate in the fumarates group remained relatively stable over time, but it progressively increased in the anti-CD20 group, with the most prominent differences observed at year 4 and beyond.

BACKGROUND:Social determinants of health (SDOH) influence cancer prevention and outcomes. Among SDOH, economic stability-including food insecurity, income, employment, and housing stability-has a major impact on health. However, data linking food security status with cancer screening completion remain limited. We examined whether lower food security status was associated with lower completion of colorectal, breast, cervical, and prostate cancer screening. METHODS:We performed a retrospective analysis of the 2018-2023 National Health Interview Survey. Analyses were limited to cancer-specific complete-case cohorts: colorectal (N = 59,849), breast (N = 30,867), cervical (N = 56,229), and prostate (N = 20,518). Food security was categorized as high, marginal, or low/very low. Screening completion was the dependent variable. Multivariable logistic regression estimated adjusted odds ratios (aORs) for screening by food security status, controlling for sociodemographic and clinical covariates. Sensitivity analyses used age-stratified eligibility definitions across survey years. RESULTS:Compared with high food security, marginal food security was associated with lower odds of screening across cancers (aOR range, 0.63-0.88), and low/very low food security showed similar or larger deficits (aOR range, 0.60-0.88). Associations were significant for all four cancers and were similar in sensitivity analyses. CONCLUSIONS:Lower food security status was associated with lower completion of cancer screening. Addressing food insecurity may improve screening equity and reduce cancer disparities. IMPACT/CONCLUSIONS:Lower food security status was associated with lower completion of guideline-recommended screening across four cancers, even after multivariable adjustment. Future work should test whether interventions addressing food insecurity can improve screening.

Sellar region neurocytoma (SELN) is a rare neoplasm whose relationship to other neurocytomas within the central nervous system (CNS) has remained unclear. Prior reports have variably classified SELN as a variant of extraventricular neurocytoma (EVN), while immunohistochemical and ultrastructural studies have suggested a hypothalamic origin. Here, we performed unsupervised clustering of DNA methylation data across a large pan-cancer reference set and identified SELN (n = 20) as distinct from other neurocytomas and regional mimics, as well as clustering with neuroendocrine tumors from other organ sites. SELN exhibited a CIMP-like phenotype, TTF1 negativity (0/8), and AVP (vasopressin) promoter hypomethylation, implicating a magnocellular hypothalamic cell of origin. In evaluable cases, a neuronal/neuroendocrine immunophenotype was observed (synaptophysin 8/8, chromogranin A 5/5) with absent pituitary transcription factor expression (PIT1 and TPIT negative 0/4). DNA sequencing (n = 5) and RNA-based fusion profiling (n = 4) did not detect recurrent mutations or gene fusions, respectively. Patients often presented with visual disturbances or headaches and spanned pediatric and older age groups (median 42 years, range 12.5-75), with no sex predilection. Despite locally aggressive imaging features in some cases (cavernous sinus invasion, carotid encasement, hydrocephalus), disease-free survival (n = 13) was comparable to central neurocytoma, with no disease-related deaths during the limited follow-up. Together, these findings support SELN as a molecularly distinct hypermethylated neuroendocrine-like epitype and clinicopathologic entity.

IMPORTANCE/UNASSIGNED:Many patients are diagnosed with atypical lesions or lobular carcinoma in situ (LCIS); however, evidence- and consensus-based guidelines for the management of many of these lesions are limited. OBSERVATIONS/UNASSIGNED:The American Society of Breast Surgeons, in collaboration with the Society of Breast Imaging and College of American Pathology, assembled a steering group to create guidelines for the management of atypical lesions and LCIS, inclusive of flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), classic LCIS (C-LCIS), and the variant LCIS forms pleomorphic LCIS (P-LCIS) and florid LCIS (F-LCIS). The natural history of ADH, ALH, and C-LCIS suggests that these lesions are associated with an elevated future breast cancer risk; therefore, patients diagnosed with these lesions should be recommended to undergo comprehensive risk assessment and counseling about breast cancer risk-reducing strategies. The magnitude of future breast cancer risk associated with P-LCIS and F-LCIS remains uncertain, yet if these lesions are determined to be hormone receptor positive, risk-reducing medications should be considered. There is no evidence that FEA is associated with an elevated future breast cancer risk. A second pathology review confirmation is recommended for ADH, should be considered for FEA, and is not necessary for ALH or LCIS. Currently available evidence supports the need to diagnostically excise most ADH, P-LCIS, and F-LCIS cases identified on core biopsy, although some ADH cases fulfilling strict criteria and multidisciplinary consensus can be observed. P-LCIS and F-LCIS require a negative margin, but ADH does not. ALH and C-LCIS can be safely observed if the core biopsy diagnosis is concordant with imaging features (ie, radiographic-pathologic concordance is established). Provided radiologic-pathologic concordance is confirmed, diagnostic excision is generally not indicated after a diagnosis of FEA alone. CONCLUSIONS AND RELEVANCE/UNASSIGNED:These guidelines provide evidence-informed, consensus-based recommendations for the management of atypical lesions of the breast, including ADH, ALH, FEA, C-LCIS, P-LCIS, and F-LCIS. Practicing clinicians who treat patients with atypical breast lesions or LCIS should consider integrating these guidelines into clinical management.

Microglia perform the function of CNS macrophages and act as the primary immune cells in the brain. They surveil the environment, phagocytose cellular debris, maintain homeostasis and respond to tissue damage. While under physiological conditions they play a role in supporting neurons, activated microglia participate directly in the degeneration of neurons in the substantia nigra, as the hallmark of the Parkinsons disease (PD). Their detrimental effects result from direct phagocytosis of dopaminergic neurons as well as via neuroinflammation and release of toxic reactive oxygen and nitrogen species. This pathological shift is driven by a complex interplay of genetic predispositions, such as LRRK2 and GBA mutations, and environmental triggers like toxins and gut dysbiosis.A central mechanism of this neurodegeneration involves extracellular α-synuclein acting as a danger signal (DAMP), which activates microglial Toll-like receptors (e.g., TLR2) to initiate a severe inflammatory cascade. Furthermore, the extreme biophysical stability of aggregated α-synuclein overwhelms the microglial endolysosomal network, leading to lysosomal failure, "frustrated phagocytosis," and the active propagation of the disease via exosomal shedding. Relieving this maladaptive chronic neuroinflammation is a primary therapeutic goal. Modern strategies aim to break this vicious cycle through precise interventions like NLRP3 inflammasome inhibition and autophagy enhancement. Concurrently, advanced fluid biomarkers, such as seed amplification assays (SAA), alongside multidimensional neuroimaging techniques (PET, SPECT, MRI), are proving crucial for detecting these early microglial and pathological changes to guide personalized, disease-modifying therapies of PD.