Faculty Bibliography

Pathological deposition of endogenous material within tissues represents a central, unifying mechanism across a broad spectrum of prevalent human diseases. Atherosclerosis and Alzheimer's disease (AD) exemplify this paradigm: atherosclerosis is driven by subendothelial accumulation of apolipoprotein B-containing lipoproteins, cholesterol crystals, and hydroxyapatite, while AD is characterized by cerebral deposition of misfolded amyloid-β (Aβ) and/or hyperphosphorylated tau. Emerging evidence implicates substantial lipid dyshomeostasis in AD pathogenesis, including lipid-droplet-accumulating microglia and widespread lipidomic disruption, blurring the categorical boundary between "lipid" and "protein" deposition diseases. Apolipoprotein A-I (apoA-I) dysfunction bridges both domains: post-translational modifications and point mutations impair reverse cholesterol transport in atherosclerosis and simultaneously promote apoA-I amyloid fibril formation in systemic amyloidosis. Across atherosclerosis, AD, systemic amyloidoses, immune complex-mediated nephropathies, crystal arthropathies, and lysosomal storage disorders, shared pathophysiologic processes emerge: production-clearance imbalance, conformational transitions favoring aggregation or crystallization, microenvironmental modulation by extracellular matrix components, and chronic sterile inflammatory responses driven by NLRP3 inflammasome activation. In this review, we synthesize deposition biology using atherosclerosis and AD as primary paradigms, integrate mechanistic insights from related disorders, highlight convergent molecular pathways including NLRP3, proteostasis, and glymphatic clearance, and discuss diagnostic and therapeutic strategies. A conceptual framework unifying these conditions as variations on a common deposition theme is proposed to guide broadly applicable precision therapies.

Nuisance property ordinances are municipal laws that penalize property owners or renters for alleged criminal activity or repeated disturbances, including emergency calls. As these laws have expanded, concerns have grown that they may disproportionately impact marginalized populations, including people who use drugs, by targeting drug-related activities and exacerbating chronic housing instability. This study examines the demographic and municipal-level characteristics associated with the presence of drug-related nuisance property ordinances (DNPOs) across major U.S. municipalities. Municipal codes were systemically analyzed for DNPOs across 482 municipalities in the U.S. DNPOs were classified as ordinances that list specific activities related to drugs, drug paraphernalia, or illegal activity as a nuisance. A chi-square test was used to compare proportions of demographic and socioeconomic characteristics between municipalities with and without DNPOs. 202 of 482 municipalities had DNPOs (41.9%). 73 of 202 municipalities, 36.1% of DNPOs, authorized eviction as a legal method of abatement. DNPOs were more likely to be found in municipalities with higher proportion of Black, non-Hispanic populations, lower median household income, higher poverty rates, higher unemployment rates, higher population density, higher proportions of renters, and moderate to higher rates of overdose (p < 0.05). DNPOs are prevalent across U.S. municipalities and frequently include eviction as a permitted or required abatement strategy. Our findings show that DNPOs are more likely to be present in socioeconomically disadvantaged communities. These findings underscore the need to further evaluate the health and equity consequences of nuisance property ordinances for people who use drugs.

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.

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.

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.

UNLABELLED:Pelvic fractures result in prolonged pain and immobility. In a randomized controlled trial of patients with pelvic fracture, whether abaloparatide (ABL) vs. placebo (PBO) improves healing at 3 months was evaluated. There was no significant difference in CT radiologic healing, physical performance, or change in pain in ABL vs. placebo. PURPOSE/OBJECTIVE:To determine if abaloparatide (ABL) vs. placebo (PBO) improves radiologic healing, pain, and functional outcome at 3 months in patients with pelvic fracture. METHODS:Postmenopausal women and men ≥ 50 years old, enrolled within 4 weeks of pelvic fracture (n = 48), were randomized to blinded ABL vs. PBO. The primary endpoint, fracture healing at 3 months, was assessed by two radiologists using a 5-point scale for cortical bridging from CT images comparing groups by Jonckheere-Terpstra test. The odds of healing (3 or 4 cortices bridged) were analyzed with Mantel-Haenszel relative risks (RR). Pain was assessed monthly by Numeric Rating Scale (NRS). The Short Physical Performance Battery (SPPB; walk speed, chair stands, and balance) evaluated functional mobility. RESULTS:Groups were balanced with a mean age = 82, 93% were female, 98% had multiple rami fractures, 67% had sacral fracture, and 36% had ≥ 1 displaced fracture. CT images at 3 months showed no significant difference in bridging score distribution (indicator of healing) in patients with ABL vs. PBO (p = 0.15) after adjusting for age, sacral fracture, displacement, or compliance. When evaluating individual fractures (n = 81), similar bridging scores were seen with ABL and PBO (p = 0.13). When patients were stratified as healed or not healed, 39% were healed with ABL and 64% healed with PBO (RR 0.61; 95% CI 0.33, 1.12). When looking at the 81 individual fractures, 47% were healed with ABL and 53% healed with PBO (RR = 0.88; 95% CI 0.55, 1.40). Using least square means controlling for age, sacral, and displaced fracture, NRS pain score was higher in the placebo than the ABL group at baseline (p < 0.05), but there were no further group differences in change in pain score SPPB and TUG scores improved over time in both groups without group differences. CONCLUSION/CONCLUSIONS:In this small study, there was no significant difference in CT radiologic healing, physical performance, or change in pain with ABL vs. placebo in patients with acute pelvic fracture. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT04249232 registered January 27, 2020.

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.

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.

CONTEXT/BACKGROUND:Osteopathic manipulative treatment (OMT) utilizes manual techniques to address somatic dysfunctions (SDs) and promote physiologic function. Although SDs commonly develop following traumatic injury, the role of OMT in postinjury remains incompletely characterized. Patients recovering from trauma frequently experience persistent pain and functional limitations requiring ongoing healthcare utilization. To address this need, we established a novel OMT for trauma program (OTP) to complement interventions for patients with subacute and chronic postinjury pain and mobility impairments. OBJECTIVES/OBJECTIVE:This study aims to evaluate the growth and effectiveness of the novel OTP over its first 3 years. METHODS:We retrospectively analyzed data for all patients treated at the OTP between January 1, 2021 and December 31, 2023. The outcomes included patient volume, relative value units (RVUs), and referral patterns as well as changes in pain, mobility, and other subjective improvement patients attributed to OMT. We performed subgroup analyses of patients who reported a mechanism of injury (MOI, "Injured") and those who did not ("No MOI"). Data are presented as percentages or medians (interquartile range [IQR]). RESULTS:During its first 3 years, the OTP provided 279 OMT sessions for 95 patients (41 [43.16 %] male and 54 [56.84 %] female; median 52 [41.50-64.50] years-old), applying a trauma-informed biomechanical OMT model. Quarterly patient encounters, RVUs generated, and new patient referrals increased per calendar-year quarter (CYQ; r=0.74, 0.62 and 0.56 with p=0.0028, 0.028, and 0.016, respectively). Referral patterns shifted from trauma/acute care surgery (T/ACS) and Physical Medicine and Rehabilitation (PM&R; 51.85 to 25.0 % and 33.33 to 2.78 %) toward OTP patient referrals and Primary Care referrals (0-19.44 % and 11.11-47.22 %). Median pain scores decreased immediately following the first OMT session (3 [2-5] on a 10-point pain scale). OTP patients whose first follow-up was within the study period (61, 64.21 %) reported a similar decrease between OMT sessions #1 and #2 (4 [3-6]). All patients reported improved mobility immediately after OMT. Additional benefits that patients attributed to the OTP included improvements in daily activity level (75.41 %), mood (60.66 %), sleep quality (36.07 %), and pain-free periods (36.07 %). The rate of immediate post-OMT complications (universally described as musculoskeletal discomfort or pain) was 2.87 %. We detected no significant differences during subgroup analyses. Median pain scores improved similarly between Injured and No MOI subgroups immediately after OMT session #1 (3 [2-5] vs. 3.5 [1.5-4.25], p=0.337) and between OMT sessions #1 and 2 (4 [3-6] vs. 4 [1.5-6], p=0.363). CONCLUSIONS:Our data demonstrate that not only is it possible to integrate a novel OTP into a level 1 trauma center but also that such a program is likely to grow significantly over time and consistently provide potentially beneficial OMT services for patients who do and do not identify a MOI. Programs like the OTP may provide a distinct modality to help improve postinjury pain and mobility limitations, among other potential benefits, although further analysis is necessary to assess causality. The present data informed updates to OTP operations, including the implementation of prospective, higher-fidelity data collection to enable more detailed and accurate analyses. Further research, including comparative studies, is warranted to explore the potential benefits of OMT for the trauma population.