Faculty Bibliography

OBJECTIVES/OBJECTIVE:Patients and experts agree that potentially inappropriate medications should be reconsidered after adverse drug events (ADEs), yet emergency providers are often hesitant to discuss deprescribing in deference to outpatient prescribers. We sought to explore patient communication preferences for deprescribing in the emergency department (ED) after an ADE. METHODS:We conducted a cross-sectional survey study of older adults aged 65 years and older presenting to a southeastern, academic ED from June 2024 to October 2024. While awaiting results, eligible participants completed a best-worst scaling survey comparing seven potential ED communication strategies for prompting deprescription of daily aspirin. The primary analysis tested whether an ED-initiated "therapeutic pause" ("Considering your bleeding, I would like you to hold your aspirin until you can discuss with your primary care provider") was preferred by > 50% of participants over a generic discharge referral to a primary care provider through a one-sided binomial test. Secondary analyses used conditional logistic regression to evaluate relative preference across all seven deprescribing phrases. RESULTS:In total, 102 patients completed the survey with a mean (SD) age of 75 years old (std dev 7). Among all respondents, 62% (95% CI, 52%-71%) preferred an ED-initiated 'therapeutic pause' of aspirin with primary care follow-up to the generic PCP deferral approach (p = 0.01). The least preferred statement was a strict deprescribing recommendation ("I do not think you need aspirin anymore"), which was selected as the least-favored communication approach in 65% of choice tasks. In conditional logistic regression, the therapeutic pause had greater odds of being selected as most preferred compared to the least preferred phrase (OR 9.3; 95% CI, 6.3-13.8). CONCLUSION/CONCLUSIONS:Our study suggests that ED physicians may take a proactive approach in addressing potential deprescribing in caring for patients with ADEs, such as initiating a therapeutic pause of aspirin after an episode of bleeding.

IMPORTANCE/UNASSIGNED:Transcatheter tricuspid valve replacement (TTVR) demonstrated superior outcomes over medical therapy in patients with severe tricuspid regurgitation (TR) in the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device II (TRISCEND II) randomized clinical trial, and received regulatory approval in the US in 2024. Contemporary real-world data on its effectiveness and safety remain limited. OBJECTIVE/UNASSIGNED:To evaluate 30-day clinical, echocardiographic, and health status outcomes of TTVR in real-world use. DESIGN, SETTING, AND POPULATION/UNASSIGNED:Retrospective cohort study of all consecutive patients who underwent TTVR in the US from February 2024 through March 2025 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients had symptomatic, severe TR despite optimal medical therapy and TTVR was deemed appropriate by a heart team. Statistical analysis was conducted from September 2025 to February 2026. EXPOSURE/UNASSIGNED:Device-enabled TTVR. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Thirty-day event rates (all-cause death, stroke, bleeding, new cardiac implantable electronic device [CIED] implantation, heart failure hospitalizations), TR reduction, and changes in health status (New York Heart Association [NYHA] functional class and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) are reported. Subgroup analyses examined the impact of baseline CIED status on outcomes. RESULTS/UNASSIGNED:Among 1034 attempted procedures at 82 centers (mean [SD] age, 77.1 [10.6] years; 69.1% female; 73.2% NYHA functional class III/IV), a valve was successfully implanted in 1017 patients (98.4%). Mild or less TR was achieved in 98.4% of patients post procedure and in 97.7% at 30 days. At 30 days, all-cause mortality was 3.1%; stroke, 0.2%; bleeding, 7.9%; new CIED, 15.9% in CIED-naive patients; and heart failure hospitalization, 3.1%. There were significant improvements in NYHA functional class (class I/II, 82.7%; P < .001) and mean KCCQ-OS score (22.4 points; P < .001) from baseline to 30 days. There were no significant differences in 30-day mortality (P = .47), heart failure hospitalization (P > .99), and functional outcomes (P = .55) when patients were stratified by baseline CIED status. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Early US real-world experience with TTVR confirms safety and effectiveness in patients with severe TR. Thirty-day outcomes are consistent with the TRISCEND II pivotal trial, demonstrating acceptable safety, near-complete TR elimination, and significant health status improvements in an older, comorbid population. Rates of new CIED implantation and bleeding were lower than randomized clinical trial experience.

Interferometric diffuse optics (iDO) has recently emerged as a promising class of near-infrared (NIR) light technologies for monitoring human brain signals associated with coherent light fluctuations. In this work, we demonstrate a line scan interferometric diffusing wave spectroscopy (iDWS) system at 1060 nm, a wavelength that has a multitude of benefits for high-speed cerebral blood flow index (BFI) monitoring. Pulsatile BFI measurements on the forehead of a moderately dark-skinned (Fitzpatrick Type V) subject with medium-length black hair up to a source-collector (S-C) separation of 5.5 cm on the forehead and 4.0 cm over the parietal cortex are demonstrated in continuous wave (CW) mode. On this high-throughput platform, we further implement a simple time-of-flight filter (TOF) via source wavelength tuning. The TOF filter can be turned on and off, and its width can be changed electronically, enabling probing different sample depths without requiring multiple S-C separations. At 4 cm S-C separation, an electronic TOF filter afforded a 2.92-fold reduction in scalp sensitivity over CW mode. With further optimization, the combination of TOF filtering with highly parallel detection in the 1060 nm range promises to improve depth sensitivity and signal-to-noise ratio of iDO in neuromonitoring applications.

BACKGROUND/UNASSIGNED:The metabolic mechanisms underlying right ventricular (RV) dysfunction are poorly understood, particularly outside of group 1 pulmonary hypertension (PH). We aimed to identify metabolites and pathways associated with RV systolic function and explored whether associations differed by pulmonary vascular resistance, PH group 1 status, and sex. METHODS/UNASSIGNED:We analyzed data from the multicenter PVDOMICS (Pulmonary Vascular Disease Phenomics) cohort. RV systolic function metrics included fractional area change (echo), global longitudinal strain (echo), and ejection fraction (cardiac magnetic resonance). We used linear regression adjusted for age, sex, body mass index, and PH group to assess associations between metabolites and RV function. Pathway enrichment analyses were used to identify pathways significantly associated with RV function. Interaction terms were assessed to determine whether metabolite associations were modified by pulmonary vascular resistance, group 1 PH status, or sex. Least absolute shrinkage and selection operator regression was used to develop metabolite-based scores for RV function, and prognostic performance was assessed. RESULTS/UNASSIGNED:There were 979 participants with plasma metabolomics and RV function data. Linear regression identified 170 metabolites that were significantly associated with all 3 RV metrics. Androgenic steroid, gamma-glutamyl amino acid, polyamine, vitamin A, fatty acid, and sterol pathways are most strongly associated with RV systolic function. Two metabolites interacted with group 1 PH status, and 6 interacted with pulmonary vascular resistance. Four androgenic steroids are associated more strongly with RV systolic function in females compared with males. Metabolite-based scores were prognostically equivalent to RV systolic function metrics and less accurate than REVEAL Lite 2 scores. CONCLUSIONS/UNASSIGNED:We provide a blueprint of metabolites and metabolic pathways associated with RV systolic function across the spectrum of PH. Novel links to vitamin A and glutathione metabolites were observed. We detected few metabolites that associated with RV systolic function differentially by group 1 PH status or degree of pulmonary vascular resistance elevation. Androgenic steroids may associate more strongly with RV systolic function in females compared with males.

BACKGROUND/OBJECTIVE/OBJECTIVE:Juvenile dermatomyositis (JDM) is a systemic autoimmune vasculopathy, which may be complicated by calcinosis of the skin and subcutaneous tissues. Calcinosis is often associated with pain, ulceration, infection, impaired mobility, and reduced quality of life, yet no gold standard exists for its detection and longitudinal monitoring. Current evaluation relies on clinical examination (history plus physical examination) with or without targeted conventional radiography, which may underestimate disease burden and expose children to cumulative doses of ionizing radiation. The EOS 2D/3D imaging system provides rapid, whole-body imaging with substantially reduced radiation exposure. Thus, we sought to explore its utility in assessing calcinosis in JDM. METHODS:In this retrospective case series, we investigated NYU pediatric patients with JDM who underwent EOS imaging for evaluation of calcinosis. EOS images and conventional radiographs were independently reviewed by 2 radiologists blinded to clinical data, with a focus on the anatomic distribution of calcinosis. RESULTS:Seven patients (5 female, 2 male, ages 10 to 17 years) met the inclusion criteria, of whom 6 underwent both EOS and x-ray imaging. EOS imaging accurately identified calcinosis of the trunk and lower extremities in all cases and detected calcinosis not previously appreciated on clinical examination or dedicated radiographs in every patient. In 2 patients, EOS imaging failed to detect all upper-extremity calcinosis, likely due to the use of standard orthopedic positioning. CONCLUSIONS:EOS imaging appears to be a valid alternative to conventional radiography for evaluating calcinosis of the trunk and lower extremities in JDM, while offering the advantages of lower radiation exposure, rapid acquisition, and broader anatomic coverage. Development of JDM-specific positioning protocols may improve the detection of upper-extremity disease.

BACKGROUND & AIMS/OBJECTIVE:Lipoprotein assembly in the small intestine and liver is critical for the transport of dietary and endogenous lipids. Pla2g12b has recently been shown to play a role in lipoprotein assembly in mice livers and zebrafish larvae. Pla2g12b knockout and mutant (MUT) mice with the C129Y missense mutation have low plasma cholesterol levels. However, the role of Pla2g12b in the intestine and the reason why C129Y mutation decreases plasma lipids are unknown. METHODS:) and WT control mice were used in parallel to study plasma lipids and lipoproteins, lipid absorption and hepatic lipoprotein production studies. Transmission electron microscopy was used to visualize lipid transit through enterocytes. RESULTS:We observed that Pla2g12b expression was the highest in the duodenum. Furthermore, male and female chow fed 3-month-old MUT mice and wildtype (WT) mice expressed similar amounts of Pla2g12b protein and several genes in lipid metabolism. Nonetheless, the MUT mice had significantly lower plasma triglyceride (TG), cholesterol, HDL-C, LDL-C, apoB48, and apoB100 levels than WT mice. Several mechanisms for lower plasma lipids and lipoproteins in MUT mice were investigated. C129Y mutation had no effect on the expression of Pla2g12b and several other proteins necessary for lipid transport. Therefore, the low plasma lipid levels in MUT mice were neither due to the absence of Pla2g12b protein nor due to reductions in critical proteins in lipid transport. Next, we addressed the role of Pla2g12b in hepatic lipid mobilization and intestinal lipid absorption. MUT livers exhibited normal TG synthesis, defective TG secretion, and enhanced fat accumulation. MUT mice also showed defective intestinal TG absorption, intracellular lipid accumulation, and elevated TG excretion in the feces. CONCLUSIONS:We propose that C129 in Pla2g12b is critical for the assembly and secretion of lipoproteins by the liver and intestine.

BACKGROUND:Flow diversion is effective for unruptured distal anterior cerebral artery (DACA) aneurysms, yet comparative data between the Silk Vista Baby (SVB) and Pipeline Embolization Device (PED) in this challenging territory remain scarce. METHODS:We conducted a retrospective multicenter study using the CRETA Registry, including consecutive patients with unruptured DACA aneurysms treated with SVB or PED. The primary endpoint was complete angiographic occlusion (O'Kelly-Marotta grade D). Secondary outcomes included procedural characteristics, clinical outcome (modified Rankin Scale), and complications. Overlap weighting was applied to account for non-randomized treatment allocation. Predictors of occlusion were explored using penalized logistic regression. A sensitivity analysis using a reduced five-variable model was performed to assess model robustness. RESULTS:137 patients were included (79 SVB, 58 PED). Within the PED group, devices included Pipeline Flex (n = 34), Pipeline Flex with Shield Technology (n = 14), and Pipeline Vantage with Shield Technology (n = 10). After overlap weighting, baseline characteristics were balanced; the effective sample size was 100.4. SVB procedures more often used a single device; PED frequently required multiple stents. Procedure duration was shorter with SVB. Complete occlusion was achieved in 69.6% (SVB) and 70.7% (PED) of aneurysms, with no significant difference in adjusted analysis (OR 1.32, 95% CI 0.59-2.96). Favorable clinical outcomes were observed in both groups, with acceptable and comparable complication rates. No variable, including device type, independently predicted complete occlusion, a finding confirmed in a reduced five-variable sensitivity analysis (aOR 1.04, 95% CI 0.47-2.31; p = 0.915). CONCLUSIONS:SVB and PED demonstrated comparable angiographic efficacy and clinical safety for unruptured DACA aneurysms. Despite procedural differences, mid-term occlusion rates and outcomes were similar. Device selection in this distal territory may be guided primarily by anatomical considerations and operator preference rather than expectations of differential performance.

INTRODUCTION/BACKGROUND:Cognitive decrements in executive function and processing speed have been found in post-9/11 Veterans who have mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD). Decision making (DM) involves the coordination of cognitive sub-processes involving different brain regions known to be impacted by mTBI and/or PTSD, and so may be expected to be compromised. The ability to incorporate context is important because it plays a role in almost every cognitive and social process. However, DM abilities, including DM that requires taking context into account, are not typically assessed or investigated in Veterans. MATERIALS AND METHODS/METHODS:We prospectively recruited Veterans deployed to Iraq or Afghanistan who had the following characteristics: (1) no TBI before deployment, (2) mTBI because of blast only, (3) current PTSD (diagnosed within 6 months), and (4) ≤49 years of age. Deployed Veterans with no mTBI or PTSD served as the comparison group. Veterans with mTBI and comorbid PTSD (mTBI + PTSD; n = 9) and Veterans without mTBI or PTSD (n = 8) performed the Cognitive Bias Task, a DM task in which participants are asked to make a decision based on preference, and the extent to which choices are influenced by contextual information is measured. To further understand any association between DM and mTBI + PTSD, participants also filled out questionnaires to measure neurobehavioral and PTSD symptoms. Because normality was violated in both groups, Fisher's Exact and Mann-Whitney tests and Spearman's rank order correlations were used. RESULTS:Although Veterans without mTBI + PTSD made context-dependent choices, Veterans with mTBI + PTSD made context-independent choices (p = .034), similar to prior research examining individuals with severe TBI and left lateralized frontal lobe brain lesions. As expected, Veterans with mTBI + PTSD also demonstrated elevated scores on the symptom measures. Symptom measure scores were correlated with Cognitive Bias Task (CBT) scores and revealed a negative correlation between somatic, and marginally cognitive and arousal symptoms, and the extent to which context was incorporated into decisions. CONCLUSIONS:Veterans an average of 4.0 years after blast injury who had active PTSD (mTBI + PTSD) did not incorporate contextual information when making their decisions. Because understanding context is required in many everyday activities, if findings replicate in studies with larger samples, clinical testing for DM difficulties and training for context incorporation may improve everyday function in Veterans with mTBI + PTSD.

Reliable structural brain measurements are essential for studying neurodegeneration and for designing adequately powered aging and Alzheimer's disease (AD) research. We evaluated the test-retest reliability of FreeSurfer 7.1 morphometric measures in 100 older adults (mean age 73.5 years) ranging from cognitively unimpaired to dementia. Each participant underwent two T1-weighted 3T MRI scans on the same scanner within a short interval (mean 5.5 weeks), minimizing biological change. Segmentation was performed in both standard cross-sectional and longitudinal FreeSurfer modes, focusing on AD-relevant volumes of entorhinal cortex, hippocampus, lateral ventricles, choroid plexus, and the AD cortical thickness signature. Reliability was quantified using absolute and root-mean-square test-retest differences, standard deviation of differences, and intraclass correlation coefficients. Longitudinal processing improved precision by 15-50% across most measures compared with cross-sectional processing, with the largest gain observed for entorhinal thickness. Larger, anatomically well-defined regions (e.g., hippocampus, AD signature) demonstrated higher reliability than small structures or those with complex geometry (e.g., entorhinal cortex, choroid plexus). Image quality, indexed by the Euler characteristic, was the only factor significantly associated with measurement variability; reliability was unrelated to age, sex, cognitive status, inter-scan interval, or amyloid/tau PET burden. Power analyses indicated that detecting a 1% within-individual change requires sample sizes ranging from 36 (AD signature) to >300 (entorhinal cortex). We observed low reliability of choroid plexus volumetry by FreeSurfer 7. These results provide practical benchmarks for expected FreeSurfer measurement variability in older adults. They highlight the advantages of longitudinal processing and rigorous quality control for research on brain aging and AD.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness characterized by disrupted physiologic vascularization followed by pathologic neovascularization, classically organized around the insulin-like growth factor-1 (IGF-1)-vascular endothelial growth factor (VEGF) axis in the retina. Increasing evidence suggests that early-life gut dysbiosis may act as an upstream modifier of this biphasic process. In this review, we synthesize human cohort studies, multi-omics analyses, and experimental animal models examining associations between the neonatal gut microbiome and ROP. Preterm infants who develop severe ROP demonstrate enrichment of facultative anaerobes and reduced acquisition of obligate anaerobes, alongside altered predicted metabolic capacity. Microbiome-derived metabolites, including short-chain fatty acids, bile acid derivatives, and lipid mediators, have been shown in experimental systems to influence systemic IGF-1 production, hypoxia-inducible factor-1α stabilization, and VEGF signaling. Rodent oxygen-induced retinopathy models offer a translation framework to assess the functional link between microbial perturbation and retinal angiogenic responses. Collectively, these findings support a conceptual microbiome-IGF-1-VEGF-retina axis in which early intestinal dysbiosis may modulate inflammatory tone, metabolic signaling, and retinal vascular development. Although current evidence remains largely associative, integrating microbiome profiling with mechanistic and longitudinal studies may clarify potential causal pathways and identify novel biomarkers or preventive strategies for severe ROP.