Faculty Bibliography

PURPOSE/OBJECTIVE:To evaluate the effect of baseline dementia on postoperative outcomes in hip fracture patients undergoing hemiarthroplasty. METHODS:A retrospective review was conducted of patients aged 55 years or older who underwent hemiarthroplasty for displaced femoral neck fracture (AO/OTA 31B) between 2012 and 2024 at a large urban academic institution. Dementia was identified by ICD-10 codes and confirmed by chart review. A 3:1 propensity score matched cohort was created using the Score for Trauma Triage in Geriatric and Middle-aged (STTGMA). Demographics and baseline characteristics were compared to ensure similarity. Outcomes included total complications, major and minor complications, periprosthetic dislocation, length of stay, ICU admission, discharge location, 30- and 90-day readmission, revision surgery, inpatient, and 30-day and 1-year mortality. RESULTS:A total of 1,030 patients were included, with 241 patients with dementia and 839 controls. After 3:1 STTGMA propensity matching, baseline characteristics were comparable (mean age 82.75 vs. 83.0 years, P = 0.065; Charlson Comorbidity Index 1.96 vs. 1.92, P = 0.42; STTGMA 0.022 vs. 0.020, P = 0.50). Patients with dementia had increased major complications (17.92% vs. 10.93%, P = 0.013), including sepsis (5.00% vs. 2.21%, P = 0.027), urinary tract infections (13.33% vs. 6.78%, P = 0.002), and hip hemiarthroplasty dislocations (6.25% vs. 2.21%, P = 0.002). Patients with dementia also had longer length of stay (7.84 ± 5.83 vs. 6.80 ± 2.24 days, P = 0.030), increased 30-day readmissions (15.83% vs. 8.85%, P < 0.001), increased 90-day readmission (20.00% vs. 11.76%, P < 0.001), and higher 1-year mortality (16.25% vs. 8.02%, P < 0.001). No differences were observed in pneumonia, stroke, myocardial infarction, cardiac arrest, venothromboembolism, acute kidney injury, anemia, and revision surgery. CONCLUSION/CONCLUSIONS:Dementia was associated with increased major complications, hip hemiarthroplasty dislocations, higher readmission, and mortality after hemiarthroplasty. These findings highlight the need for targeted perioperative planning and multidisciplinary care pathways in cognitively impaired patients.

BACKGROUND:Emerging evidence suggests endocrine disrupting chemicals, including bisphenols and phthalates, may affect behavioral development in children and adolescents. Risk behavior constitutes a potentially sex hormone sensitive behavioral construct. Here, we examined longitudinal associations of phthalate and bisphenol exposure with performance-based tasks and self-reported risk-taking behaviors. METHODS:Within a population-based birth cohort in the Netherlands, urinary bisphenols and phthalate metabolite concentrations were measured in women during pregnancy (three times, n = 1379) and in children (once at 6 years, n = 775). At 10 years, child risk-taking behavior was assessed with the computerized experimental Columbia Card Task (CCT). At 14 years, adolescents completed a computerized self-assessment of real-life risk-taking behaviors. Linear regression and hurdle models adjusted for confounders were applied in the whole sample and stratified by sex at birth. RESULTS:After multiple testing correction, no associations in all children or in boys were found for prenatal or childhood phthalate exposure with the average CCT-score. In girls, prenatal mono-isobutyl phthalate was associated with a higher average CCT-score, indicting more risk-taking (B per 10-fold increase in creatinine-adjusted average prenatal levels = 2.10, 95% CI: 0.69,3.52). No associations were observed for bisphenol exposure nor for self-reported risk-taking. CONCLUSIONS:Prenatal phthalate exposure was associated with more risk-taking in an experimental task at 10 years-of-age in girls only. The task reflects risky decision-making, which may be a hormonally sensitive construct. Risky decision making potentially precedes real-life risk-taking, which was captured by the self-reported measure and was limited in this young sample.

IMPORTANCE:The relative efficacy and safety of oral P2Y purinergic receptor 12 (P2Y12) inhibitors (clopidogrel, ticagrelor, or prasugrel) after percutaneous coronary intervention (PCI) are not well defined. OBJECTIVE:To assess the efficacy and safety of oral P2Y12 inhibitors in patients who underwent PCI. DATA SOURCES AND STUDY SELECTION:PubMed and Embase were searched until November 15, 2025, for randomized clinical trials comparing at least 2 of the 3 agents. DATA EXTRACTION AND SYNTHESIS:Data were abstracted by 2 independent authors according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Random-effects odds ratios (ORs) and 95% confidence intervals were calculated. Data were analyzed in December 2025. MAIN OUTCOMES AND MEASURES:The primary efficacy outcome was major adverse cardiovascular events (MACE), while the primary safety outcome was major bleeding. The primary analysis compared prasugrel and ticagrelor in reference to clopidogrel using a mixed treatment comparison meta-analysis. RESULTS:Data were analyzed from 15 randomized clinical trials that included 48 904 patients (mean [SD] age, 63.2 [4.21] years; 13 330 female patients [27.3%]). Compared with clopidogrel, there was a lower risk of MACE (OR, 0.80; 95% CI, 0.69-0.93) driven by lower myocardial infarction (OR, 0.71; 95% CI, 0.62-0.82) and stent thrombosis (OR, 0.48; 95% CI, 0.37-0.62) with prasugrel. MACE was not reduced with ticagrelor compared with clopidogrel, although there was lower stent thrombosis (OR, 0.73; 95% CI, 0.59-0.91). Furthermore, there was lower risk of MACE with prasugrel compared to ticagrelor (OR, 0.83; 95% CI, 0.70-0.98) driven by lower myocardial infarction (OR, 0.78; 95% CI, 0.65-0.94) and stent thrombosis (OR, 0.66; 95% CI, 0.49-0.88). There was a higher risk of major bleeding with ticagrelor vs clopidogrel (OR, 1.24; 95% CI, 1.01-1.52) driven by higher intracranial hemorrhage (OR, 1.89; 95% CI, 1.08-3.33). Prasugrel ranked first, followed by ticagrelor and clopidogrel, for MACE, myocardial infarction, and stent thrombosis. CONCLUSIONS AND RELEVANCE:In this systematic review and meta-analysis of 15 randomized clinical trials in patients who underwent PCI, prasugrel provided the optimal balance between efficacy and safety compared with ticagrelor and clopidogrel.

Acute myeloid leukemia (AML) is a blood cancer with poor survival outcomes. Acute respiratory failure frequently occurs due to leukemia infiltration of the lungs. Underlying mechanisms remain unexplored and therapeutic interventions remain empiric. Here we map the AML lung microenvironment at spatial and single-cell resolution. We show that extensive remodeling is coupled with inflammation and impaired tissue integrity and function. Steroid treatment significantly reduces AML burden and lung infiltration, improving oxygenation and pulmonary function. As a mechanistic correlate, the S-type lectin Lgals9 is triggered by inflammation and mediates cell-cell interactions within infiltrated lungs. Also, the alarmin IL-33 and its receptor (IL-1RL1) are involved in cell-cell interactions within the leukemic lung microenvironment. Targeting either the Lgals9 or IL-33 axis significantly decreases overall AML burden and lung infiltration through effects on both the immune microenvironment and AML cells. Our studies delineate pulmonary infiltration phenotypes in acute leukemia, enabling new treatment strategies.

BACKGROUND/UNASSIGNED:Racial and ethnic disparities are a concern in lung cancer screening. OBJECTIVE/UNASSIGNED:To investigate the performance of risk prediction models to define screening eligibility across 4 U.S. racial and ethnic groups. DESIGN/UNASSIGNED:Cohort study. SETTING/UNASSIGNED:United States, Lung Cancer Cohort Consortium. PARTICIPANTS/UNASSIGNED:641 830 participants aged 50 to 80 years with a smoking history from 12 U.S. cohorts, including 6390 Asian, 9781 Hispanic, 39 872 non-Hispanic Black, and 585 787 non-Hispanic White participants. MEASUREMENTS/UNASSIGNED:Calibration and discrimination were quantified for 16 lung cancer prediction models. Then, screening-related metrics were calculated after applying model thresholds to select the same number of eligible participants as the 2021 criteria from the U.S. Preventive Services Task Force (USPSTF-2021). These included eligibility, sensitivity, and efficiency measured as estimated number needed to screen (NNS; the ratio between participants and lung cancer cases) for each strategy or prediction model in each racial and ethnic group. RESULTS/UNASSIGNED:General patterns across the 16 models included substantial underestimation of lung cancer risk in non-Hispanic Black participants (expected-observed ratio < 0.75 for 11 of 16 models), lower discrimination in Asian participants than all other groups (13 of 16 models), and lower discrimination in non-Hispanic Black than non-Hispanic White participants (15 of 16 models). When a same-sized screening-eligible population as USPSTF-2021 (38.0%) was enforced, all risk-based strategies achieved better average estimated screening efficiency and reduced racial and ethnic differences in efficiency compared with USPSTF-2021. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 (PLCOm2012) and Life Years gained From Screening-Computed Tomography model (LYFS-CT) performed best (mean estimated NNS, 36.5 [SD, 8.8] and 40.1 [SD, 8.2], respectively). However, no strategy could simultaneously optimize eligibility, sensitivity, and efficiency while also reducing racial and ethnic differences. LIMITATION/UNASSIGNED:Smaller sample for Asian and Hispanic participants. CONCLUSION/UNASSIGNED:To optimize efficiency and minimize its variation across racial and ethnic groups, risk-based strategies were superior to USPSTF criteria. Further optimization of prediction models for the diverse U.S. population is needed. PRIMARY FUNDING SOURCE/UNASSIGNED:U.S. National Cancer Institute, Lung Cancer Research Foundation, and Cancer Research UK.

BackgroundPeople with subjective cognitive decline (SCD) are at increased risk of Alzheimer's disease. Prior research has suggested that amygdala volume may be more sensitive than hippocampal volume in detecting differences between SCD and age-matched controls, as well as in predicting SCD conversion to mild cognitive impairment. However, the microstructure underlying this volumetric change remains unclear.ObjectiveThis study evaluated amygdala microstructural differences in SCD versus control participants as well as associations between amygdala microstructure and volume, age, memory performance, anxiety, and depression using diffusion imaging.MethodsDiffusion tensor imaging, diffusion kurtosis imaging, and neurite orientation dispersion and density imaging were fit to diffusion MRI images. Group differences and correlations between diffusion metrics, age, memory, anxiety, and depression were assessed in 123 SCD versus 194 age-matched controls over age 55.ResultsIn the left amygdala, SCD participants had significantly lower fractional anisotropy (FA), lower kurtosis fractional anisotropy (KFA), and higher free water fraction (FWF). KFA was lower in the right amygdala in SCD. There were no significant group differences in the amygdala volume. Bilateral KFA negatively correlated with FWF, a marker of neuroinflammation and neurodegeneration. Left FA negatively correlated with orientation dispersion index, a marker of neuritic branching. Right KFA correlated with age only in SCD, while left FA correlated with anxiety only in controls.ConclusionsKFA is sensitive to group differences between SCD and controls in bilateral amygdala. KFA may reflect neuroinflammation and increased sensitivity to aging in the amygdala in SCD.

PURPOSE/OBJECTIVE:To investigate intravitreal anti-VEGF drug use among Medicare Fee-For-Service (FFS) and Medicare Advantage (MA) beneficiaries. DESIGN/METHODS:Retrospective, cross-sectional analysis of de-identified healthcare data from the American Academy of Ophthalmology's IRIS® Registry (Intelligent Research in Sight) for patient encounters between January 2017 to December 2022. PARTICIPANTS/METHODS:Medicare beneficiaries 65 years and older with FFS or MA coverage with continuous insurance enrollment for at least12 months. METHODS:Unique FFS and MA beneficiaries receiving intravitreal anti-VEGF were included. Patients were considered to be treated with a particular drug if more than 50% of their injections for at least 12 months were with that drug. For each anti-VEGF drug, we compared proportions of patients treated (more than 50% of their injections) with that drug between FFS and MA and calculated the difference in use between the two Medicare health care programs. MAIN OUTCOME MEASURES/METHODS:Differences in anti-VEGF drug utilization between FFS and MA. RESULTS:930,411 beneficiaries underwent 12,942,057 intravitreal injections. In the FFS group, aflibercept 2mg was used most frequently (43.8%; n = 4,271,050), followed by bevacizumab (34.7%; n = 3,382,439), ranibizumab (20.6%; n = 2,008,791), brolucizumab (0.6%; n = 56,728) and faricimab (0.4%; n = 40,729). In the MA group, bevacizumab was used most frequently (45.1%; n = 1,436,151), followed by aflibercept 2mg (37.8%; n = 1,201,311), ranibizumab (6.5%; n = 524,758), brolucizumab (0.4%; n = 13,406), and faricimab (0.2%; n = 6,694). Repackaged bevacizumab (lower cost) was more common in the MA group compared with the FFS group (60.0% vs. 47.0%; difference (diff) = 13.0%, 95% CI:12.8, 13.3%; P<.001). Higher cost drugs were used significantly less often among persons with MA compared with FFS, respectively (aflibercept 2mg (28.9 vs. 36.6%; diff = -7.7%; 95% CI -7.9%, -7.4%; P<.001), ranibizumab (11.9% vs. 16.8%; diff = -4.9%; 95% CI -5.03%, -4.7%; P<.001), faricimab (0.06% vs. 0.24%; diff = -0.18%; 95% CI -0.19%, -0.16%); P<.001, and brolucizumab (0.12% vs. 0.19%; diff = -0.07%; 95% CI -0.09%, -0.05%; P<.001). CONCLUSIONS:Beneficiaries enrolled in MA were less likely to receive higher cost, anti-VEGF drugs, raising concerns about reduced beneficiary access to newer more expensive anti-VEGF drugs in MA.

INTRODUCTION/UNASSIGNED:Excess cumulative fluid balance is a common complication impacting critically ill pediatric patients that is associated with worse clinical outcomes. Nevertheless, there are inconsistent practices in recognizing and reducing excess fluid balance. PURPOSE/UNASSIGNED:Assess contextual factors that inform fluid-based practices across four pediatric intensive care units. METHODS/UNASSIGNED:We conducted semi-structured interviews across 4 PICUs from August to October 2025. Through an iterative process informed by prior survey data, we followed the established implementation science Reach, Effectiveness, Adoption, Implementation, Maintenance/Practical Robust Implementation and Sustainability Model framework to develop an interview guide. Questions explored fluid balance recognition and reduction. Participants were recruited using purposive sampling via email recruitment. We used Rapid Assessment Procedures with two independent coders. Thematic saturation was reached within the first round of interviews. RESULTS/UNASSIGNED: = 3). Institutions had balanced numbers of interviews. Theme 1 centered on the limitations of data used for fluid balance recognition, namely that these data are affected by patient variability, rely on subjective exam findings, and depend on inaccurate tools. Theme 2 highlighted insufficient emphasis on limiting unnecessary fluid administration. Theme 3 addressed cultural barriers including educational gaps, lack of standardization, entrenched unit practices, and insufficient communication. DISCUSSION/UNASSIGNED:These themes highlight the need for accurate data reporting, shifts in emphasis of fluid management, and cultural/systemic changes. We theorize that these suboptimal approaches to fluid balance management could inform clinical decision support tools, research priorities, and quality improvement initiatives.