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Background Sinonasal pathology, such as chronic inflammatory disease or neoplasm, can cause secondary nasolacrimal duct obstruction (sNLDO). There is a paucity of data on dacryocystorhinostomy (DCR) techniques and outcomes for NLDO secondary to known sinonasal pathologies. Objective To describe case characteristics, management, and surgical outcomes of sNLDO at a tertiary academic center. Methods Charts of DCR cases with at least 3 months follow-up done at a single institution over a 5-year period (2018-2022) were reviewed. Patient and surgical characteristics were recorded and compared between secondary and primary NLDO groups. The primary outcome was early functional success of DCR, assessed by improvement or resolution of epiphora at 3 months. Results A total of 236 cases were included. Of those, 79 (33.5%) were classified as secondary NLDO associated with sinonasal pathology. Reasons for sNLDO were sinonasal cancer (46.8%), chronic inflammatory disease (24.1%), trauma (16.5%), or prior head and neck radiation (31.6%). When comparing primary acquired NLDO to sNLDO cases, DCR for sNLDO was more likely to be performed endoscopically (68.4% vs 31.8%, P < .01), by a multidisciplinary team of rhinologist and oculoplastic surgeon (70.9% vs 8.3%, P < .01), and required bilateral surgery (36.7% vs 5.7%, P < .01). The overall functional success rate was 79.7% for sNLDO compared to 87.9% for primary acquired NLDO ( P < .01). Revision surgery for sNLDO, history of sinonasal malignancy, and radiation were associated with lower functional success rates (66.7%, 70.3%, and 68.0%, respectively). Canalicular pathology was more common in sNLDO cases (29.0% vs 8.3%, P < .01). Conclusions Secondary NLDO was more commonly managed with an endoscopic approach by a multidisciplinary team. Revisions for sNLDO, as well as cases with a history of sinonasal malignancy and radiation, had a markedly lower success rate, and sNLDO was frequently associated with canalicular obstruction. These findings may facilitate surgical planning and patient counseling.

Abstract INTRODUCTION Few African American (AA) donors have been included in post mortem Alzheimer's disease (AD) studies compared to European‐ancestry (EA) individuals. METHODS We generated transcriptome‐wide bulk pre‐frontal cortex (PFC) gene expression data from 125 AA donors with neuropathologically determined AD and 82 AA controls. RESULTS Transcriptome‐wide significant differential expression was observed with 482 genes. The most significant, ADAMTS2 , showed 1.52 times higher expression in AD cases ( p = 2.96x10 −8 ). Comparison of findings with those from a recent gene expression study of EA brain donors revealed substantial concordance, including ADAMTS2 . Other associations not observed in EA results may be especially relevant to AD risk in the AA population. Examination of AA AD GWAS‐implicated variants identified several expression quantitative trait loci. CONCLUSION This first large‐scale AA brain AD gene expression study identified many differentially expressed genes, including ADAMTS2 , and supports gene expression as a molecular pathway underlying the impact of several AA AD risk variants. Highlights We performed the largest African American brain tissue Alzheimer's disease (AD) gene expression study. Expression differences for 482 genes, notably ADAMTS2 , were study‐wide significant. Many significant differentially expressed genes are involved in energy metabolism. Several previously known AD‐associated variants in African Americans are eQTLs. These results advance knowledge of the genetic basis of AD in the AA population.

ABSTRACT Objective Data on bone health in patients with mild autonomous cortisol secretion (MACS) are limited and heterogenous. We sought to assess the prevalence of osteoporosis and symptomatic fragility fractures in patients with adrenal adenomas and hypercortisolism, and explore associations with the degree of cortisol excess and frailty. Design This multicenter cross ‐sectional study involved prospective enrollment of adults with nonfunctioning adrenal adenomas (NFA), MACS, Cushing syndrome (CS) and referent subjects without adrenal disorders during the study period (January 2019–September 2022). All participants completed a bone health questionnaire at enrollment and had dual‐energy X ‐ray absorptiometry bone mineral density assessment within 12‐months. Final analyses were adjusted for age, sex, body mass index, smoking status, alcohol use. Results Participants included 117 with NFA (median age 62 years, 80% women), 191 with MACS (median age 63 years, 74% women), 62 with CS (median age 50 years, 92% women), and 101 referent subjects (median age 59 years, 47% women). Both patients with CS (OR: 3.0, 95% CI: 1.1–8.3) and MACS (OR: 2.2, 95% CI: 1.9–4.9) had a higher prevalence of osteoporosis when compared to referents. Among patients with MACS, only those with post 1‐mg dexamethasone suppression test (post‐1mg‐DST) cortisol > 83 nmol/L had a higher prevalence of osteoporosis when compared to referents (OR: 3.2, 95% CI: 1.4–7.5) and NFA (OR: 2.2, 95% CI: 1.1–4.4). For clinical fragility fractures, only patients with CS showed an increased prevalence when compared to referents (OR: 6.1, 95% CI: 1.7–26.4) and NFA (OR: 3.8, 95% CI: 1.3–11.2). Prevalence of clinical fragility fractures was similar to referents in patients with MACS (OR: 1.8, 95% CI: 0.6–6.9) and NFA (OR: 1.5, 95% CI: 0.4–6.1), and was not associated with post‐1mg‐DST cortisol or frailty in the MACS and NFA groups. Conclusion Patients with CS, and those with MACS and post‐1mg‐DST cortisol > 83 nmol/L, exhibited a higher burden of osteoporosis. However, only CS was associated with an elevated risk of symptomatic fragility fractures.

ABSTRACT Newly diagnosed patients with non‐Hodgkin lymphoma (NHL) often have a history of other diseases, and these comorbidities can impact patient treatment and management options, as well as overall survival (OS). We developed the Lymphoma Epidemiology of Outcomes (LEO) comorbidity index (LCI) as a sum of 10 comorbidities adapted from the Self‐Report‐Generated Charlson Comorbidity Index (SRG‐CCI) for use in the LEO cohort, a national prospective study of newly diagnosed NHL. Of the 5502 participants with self‐reported comorbidity data, 3107 (56.4%) were male and the mean age at diagnosis was 60.9 years (range, 18–99 years). The LCI ranged from 0 to 6, with 48.6% having 0, 30.2% having 1, 21.2% having 2 or more comorbidities. With a median follow‐up of 62.4 months among surviving participants, 2099 patients had an event and 1219 died. Continuous LCI similarly predicted both 1‐year mortality (c‐statistic = 0.654) and OS (c‐statistic = 0.655), while it showed a weaker but still statistically significant predictive ability for lymphoma‐specific (c‐statistics = 0.617) and event‐free (c‐statistic = 0.574) survival. Participants with 1 (HR = 1.21, 95% CI 1.05–1.39) and 2+ (HR = 1.80, 95% CI 1.56–2.08) comorbidities had inferior OS compared to those with no comorbidities after adjustment for age and sex (c‐statistic = 0.654), and performance strengthened after adjustment for the International Prognostic Index (c‐statistic = 0.672). LCI predicted OS most strongly in marginal zone (c‐statistics = 0.748) and weakest in T‐cell (c‐statistic = 0.579) lymphoma. The cumulative incidence of death due to lymphoma, lymphoma treatment, and other causes all increased with increasing comorbidities, with the greatest increase observed for death due to other causes. The LCI performs comparable to other published comorbidity indices, supporting its use in the LEO cohort to better model real‐world outcomes and more generally providing an approach to implementing comorbidity indices in cancer survivorship cohorts.

Objective: To examine prospective associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test positivity, coronavirus disease 2019 (COVID-2019) symptom severity, and COVID-2019 hospitalization with incident clinical diabetes among aging women. Methods: A cohort study was conducted using data from 34,405 eligible Women’s Health Initiative participants who completed ≥1 COVID-2019 surveys (Survey 1: June–December 2020; Survey 2: June 2021–February 2022) and were followed up for an average of 1.86 (±0.49) years, yielding 399 incident diabetes cases. Results: SARS-CoV-2 test positivity was associated with diabetes risk in the age-adjusted Cox regression model (hazard ratio [HR] = 1.76, 95% confidence interval [CI]: 1.10, 2.82), but not when fully adjusted (HR = 1.43, 95% CI: 0.88, 2.31). Diabetes risk was higher among those with 1–2 COVID-19 symptoms (HR = 1.39, 95% CI: 1.09, 1.77) and those with 3± COVID-2019 symptoms (HR = 1.53, 95% CI: 1.06, 2.22) compared with those without COVID-2019 symptoms in fully-adjusted models, irrespective of self-reported SARS-CoV-2 testing. COVID-2019 hospitalization was associated with 2–3 times the risk of clinical diabetes in age-adjusted (HR = 2.95, 95% CI: 1.52, 5.72) and fully-adjusted (HR = 1.90, 95% CI: 0.97, 3.72) models. Conclusions: Age-adjusted self-reported SARS-CoV-2 test positivity was associated with a higher incidence of diabetes. Reporting of COVID-2019 symptoms and being hospitalized for COVID-2019 were each associated with higher incidence of diabetes in aging women, after controlling for demographic, socioeconomic, lifestyle, and health characteristics.

406 Background: Anxiety is highly prevalent among oncology patients, often arising from uncertainty around diagnosis, treatment options, and prognosis. Elevated anxiety can impair decision-making, reduce treatment adherence, and diminish overall quality of life. Effective second opinion consultations may help mitigate anxiety and increase patients’ confidence in recommending healthcare services to others. Our study evaluates the impact of oncology second opinion (OSO) consultations on anxiety level (AL) and confidence in the organization (CIO) providing the second opinion, i.e., Cincinnati Cancer Advisors (CCA) and Naples Cancer Advisors (NCA). Methods: The study included patients with cancer diagnoses, age ≥18 years, who were served in person for OSO at CCA and NCA. A survey was used before and after consultation, measuring AL (scale 1- 10) and CIO level (scale 1 - 10), assessed by asking patients how likely they would refer loved ones to the organization. After the content and face validation, patients completed the survey anonymously, put it in a sealed envelope, and dropped it in a dedicated box. Data was analyzed using paired t-tests to compare the change from pre- to post-consultation scores. Spearman’s correlation test was used to assess the relation between the changes in AL and CIO. Statistical significance was assessed using an alpha-level of 0.05. Analyses were conducted via R and R Studio (version 2025.5.1.513). Results: Overall, 46 consecutive patients participated (45 completed AL pre and post visit survey and 43 completed the CIO pre and post visit survey). The mean pre-consultation anxiety score was 5.92 (SD = 2.58), and the post-consultation score was 3.87 (SD = 2.10), demonstrating a significant reduction (mean paired difference = -2.05; p < 0.0001). The mean pre-consult CIO was 8.21 (SD = 2.03), increasing to 9.73 post-consultation (SD = 0.53), indicating a significant improvement (mean paired difference = 1.66; p < 0.0001). The correlation between changes in AL and CIO was not statistically significant, which may be attributed to the high baseline CIO scores (ceiling effect) and the small sample size. Conclusions: Oncology second opinion was associated with a marked decrease in patient AL and a significant increase in CIO. The patient survey will continue to recruit additional participants to increase the sample size and explore the correlation between changes in AL and CIO. Studying the downstream impact on patient experience and outcome is warranted.

Abstract While many postmitotic cells in the body harbor cilia, certain aggressive cancers such as glioblastoma (GBM) display low frequencies of cells harboring a primary cilium. Ciliated GBM cells that plan to multiply have to disassemble their cilium in order for centrioles to duplicate and re-purpose for mitosis. Little is known about the molecular mechanisms underlying cilia disassembly in GBM, or whether this may represent a driving factor in disease onset, progression, or recurrence. In many cell types, ciliary disassembly is thought to be orchestrated by the aurora kinase A (AURKA) and histone deacetylase 6 (HDAC6) signaling axis. These molecules are often overexpressed in GBM, perhaps owing to the less frequent observation of ciliated GBM cells. Here, we review regulators of the core pathway, and discuss recent studies attempting to inhibit AURKA and HDAC6 in patient and mouse models of GBM and resulting effects on cilia. In the face of potent inhibitors, GBM cells appear to engage pathways independent of the core axis to promote cilia disassembly and/or engage other forms of modified axonemal tubulin to ensure persistence of cilia on GBM cells. GBMs upregulate a host of proteins implicated to drive cilia disassembly. Thus, clarifying these alternate mechanisms may be important as the roles of cilia in tumor formation and propagation, angiogenesis, and treatment resistance are increasingly reported. A deeper understanding of the role of cilia in these hallmarks of glioma may hold clues to the high recurrence rate of GBM.

Abstract Chimeric antigen receptor (CAR) T-cell (CAR-T) treatment for B-cell acute lymphoblastic leukemia (ALL) induces high initial response rates, but most patients relapse. Low disease burden (often defined as &lt;5% blasts in the bone marrow) is associated with better outcomes. CAR HEMATOTOX (HT) is a score using prelymphodepletion hematologic and inflammatory parameters to predict outcomes in lymphoma. Here, we assess its prognostic utility in a large multicenter adult B-cell ALL cohort. Patients who received brexucabtagene autoleucel across 33 centers in North America were included as part of the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) consortium. An independent cohort of 61 patients with ALL treated with an investigational CD19 CAR-T therapy at 1 center was also described. Among 199 ROCCA consortium patients, 43 (22%) patients with HTlow scores had lower rates of delayed neutrophil recovery than those with HThigh scores (26% vs 52%, P = .002) and fewer severe infections (2.5% vs 18.8%, P = .011). They also had higher response rates, overall survival (OS), and event-free survival (EFS), as well as lower nonrelapse mortality and cumulative incidence of relapse. The survival differences remained significant after multivariable adjustment for disease burden and other covariates. In the investigational cohort of 61 patients, patients with HTlow scores had improved OS and EFS, as well as higher peak CAR-T expansion. In summary, CAR HT score is a prognostic factor independent of disease burden in adult ALL. HTlow score is associated with superior outcomes after CD19 CAR-Ts and higher CAR-T expansion in a single-center cohort. These trials were registered at www.clinicaltrials.gov as #NCT01044069 and #NCT01860937.

Introduction: Percutaneous nephrolithotomy (PCNL) has been a mainstay treatment for large stone burdens since the 1980s, historically offering improved stone-free rates over retrograde intrarenal surgery (RIRS). Gaining optimal access into the renal collecting system can be challenging, requiring advanced skills or interventional radiology assistance. The learning curve for fluoroscopic and ultrasonography access can be steep, with only a minority of PCNL access performed by urologists in the United States. This study compares robotic-assisted electromagnetic (EM) guidance to traditional fluoroscopy for obtaining percutaneous renal access between cohorts of novice and expert urologists. Methods: Ten novices and five expert urologists used robotic-assisted EM guidance to obtain access in a modified supine position compared with using fluoroscopy in a traditional prone position in human cadavers. Primary success was defined as papillary access. Performance metrics, including number of puncture attempts, time to access, radiation exposure, and participant confidence, were compared between novices and experts. Results: Robotic-assisted EM guidance improved success rates for both novices (100% vs 70%) and experts (93% vs 87%) compared with fluoroscopy. Novices showed greater accuracy using robotic assistance (97% vs 37%). The number of insertion attempts decreased with robotic guidance for both groups (novices: 3.42 ± 0.44 vs 1.47 ± 0.19; experts: 2.13 ± 0.36 vs 1.40 ± 0.24; p < 0.002). EM guidance ( p < 0.05) and experience ( p < 0.05) significantly reduced the time from needle insertion to access (novices: 12.86 ± 2.41 minutes vs 4.49 ± 0.96 minutes; experts: 4.90 ± 1.40 minutes vs 4.09 ± 1.12 minutes). Radiation exposure was notably lower with EM guidance (novices, 1.12 ± 0.17 mGy vs 4.86 ± 0.70 mGy; experts, 0.69 ± 0.12 mGy vs 4.11 ± 1.21 mGy; p < 0.001). Novices felt more confident (5[3–5] vs 2[1–4], p < 0.001) and at ease (5[3–5] vs 2.75[1–3], p < 0.001) with EM guidance. Conclusion: Robotic-assisted EM guidance improves percutaneous access success, reduces attempts and radiation exposure, and enhances novice confidence and accuracy. This technology could enable urologists to more effectively and safely perform PCNL, especially for less experienced practitioners.

Purpose: Surgical video review can be used in urologic training, yet significant barriers to the implementation of video review programs exist, and formal assessment of usage and utility for trainees is limited. Here, we evaluate a novel video review platform to describe patterns of use and determine perceived utility. Materials and Methods: We analyzed learning points entered by trainees during video review of radical prostatectomy cases using our surgical intelligence–enabled Film Room platform between September 2023 and July 2024. Learning point content was categorized according to surgical coaching domains as technical, cognitive, nontechnical, or descriptive. Entries were compared by surgical step and level of training. Anonymous surveys were distributed to trainees to determine perceived utility and reveal patterns of video review. Results: Thirteen trainees entered 480 unique learning points across all radical prostatectomy steps and spanning surgical coaching domains during the study period. Learning points varied by training level, with junior trainees entering points more often than senior trainees for Retzius-space dissection ( N = 73 vs 17, p < 0.01) and seminal vesicle and posterior dissection ( N = 58 vs 27, p < 0.01). Trainees used video review in preparation for both upcoming cases and performance analysis. Ninety-four percent of survey respondents reported they either agreed or strongly agreed that video review helped them develop surgical skills. Conclusions: We found usage across training levels and high perceived utility of our Film Room platform for video review of robotic prostatectomy. Implementation of video review platforms holds promise to augment existing urologic training and should be explored further.