Faculty Bibliography

PURPOSE/OBJECTIVE:Brain metastases (BMs) from male breast cancer (MBC) are exceptionally rare, and the efficacy and safety of stereotactic radiosurgery (SRS) in this population remain poorly characterized. METHODS:We conducted a multicenter retrospective cohort study across 12 institutions. Eligible patients had histologically confirmed MBC with histopathologically or radiologically documented BMs treated with SRS. Lesion-level outcomes were analyzed using generalized estimating equations (GEE) with robust variance estimation. Overall survival (OS) was estimated by the Kaplan-Meier method. Neurological symptom change was assessed with McNemar's exact test, and discriminative ability of dosimetric variables for local failure was evaluated using receiver operating characteristic (ROC) analysis. RESULTS:Nineteen patients harboring 185 SRS-treated lesions were included. Median age at SRS was 59.0 years. The overall crude local control rate was 97.3%. Median OS was 28.0 months. Patients with controlled systemic disease at SRS demonstrated significantly longer median OS than those without (40.0 vs. 22.0 months; p = 0.032). Target volume was the only significant discriminator of local failure on ROC analysis (p < 0.001; optimal threshold 0.98 cc) and independently predicted adverse radiation effects on GEE analysis (p = 0.013). Neurological symptom burden decreased significantly after SRS (63.2% to 26.3%; p = 0.016), and median Karnofsky Performance Status remained stable. CONCLUSION/CONCLUSIONS:SRS achieves high local control with a favorable safety and neurological profile in MBC BMs. Systemic disease control at the time of SRS is the primary determinant of survival, while target volume is the principal dosimetric predictor of both local failure and radiation toxicity. These findings support the application of established SRS practice parameters in this rare population.

OBJECTIVES/OBJECTIVE:Small Woven EndoBridge (WEB) devices (≤ 4.5 mm) for the intracranial aneurysm treatment are technically challenging to deploy, with limited efficacy and safety data. This study compared functional, angiographic, and safety outcomes of small WEBs with large (> 4.5 mm) and very large (> 7.5 mm) WEBs. MATERIALS AND METHODS/METHODS:The WorldWideWEB consortium is a retrospective, multicenter collaboration across 30 international institutions including adults with intracranial aneurysms treated with WEB. Patients were stratified into small (≤ 4.5 mm) and large (> 4.5 mm) groups; a subanalysis compared small with very large (> 7.5 mm) devices. Primary outcome was retreatment rate. Secondary outcomes included modified Rankin Scale (mRS), angiographic outcomes periprocedurally and last follow-up (FU), and safety events (intracranial hemorrhage (ICH) and thromboembolic complications (TECs)). RESULTS:Among 1473 patients, 229 (15.5%) received small WEBs. Baseline characteristics were similar. Small WEBs showed lower retreatment (4.3% vs 8.8%, p = 0.04) and higher complete occlusion (periprocedurally: 57.1% vs 36.6%, p < 0.01; FU: 76.2% vs 58.5%, p < 0.01). Median mRS was comparable (1 [1-2] vs 1 [1-2], p = 0.88), as was safety (ICH 2.6% vs 0.9%, p = 0.10; TECs 3.1% vs 3.9%, p = 0.69). Very large WEBs had higher retreatment (16.1%, p < 0.001) and lower complete occlusion (periprocedurally: 32.2%, p < 0.001; FU: 50.5%, p < 0.001), with comparable safety (ICH 0.9%, p = 0.27; TECs 4.5%, p = 0.51). CONCLUSION/CONCLUSIONS:Small WEBs demonstrated lower retreatment, superior anatomic and comparable clinical outcomes compared with large devices, with similar safety profiles. KEY POINTS/CONCLUSIONS:Question Do small Woven EndoBridge devices have comparable efficacy and safety to larger devices for intracranial aneurysm treatment despite technical deployment challenges? Findings Small Woven EndoBridge devices (≤ 4.5 mm) achieved lower retreatment rates and superior angiographic occlusion compared with larger devices, with similar safety and functional outcomes. Clinical relevance These findings support the use of small Woven EndoBridge devices for appropriately sized aneurysms, providing reassurance that deployment challenges do not translate into worse clinical outcomes, while superior anatomic outcomes may encourage their broader adoption in clinical practice.

PURPOSE OF REVIEW/OBJECTIVE:To describe the relationship between reflux and bronchiectasis and to appraise recent literature on reflux characterization, clinical outcomes, and management strategies in patients with bronchiectasis. RECENT FINDINGS/RESULTS:Reflux is common in bronchiectasis and has been linked to worse respiratory symptoms and quality of life, more exacerbations and healthcare use, lower lung function, and higher mortality. These associations are seen across several cohorts, but nearly all data are observational, use variable reflux definitions, and cannot determine whether reflux contributes to bronchiectasis progression or simply identifies patients with more severe disease. Proposed pathways include microaspiration-related airway injury, reflex-mediated cough amplification, and microbial dysbiosis. No randomized bronchiectasis-specific trial has shown improved respiratory outcomes with reflux-directed therapy, and acid suppression alone is unlikely to address nonacid reflux, microaspiration, cough-reflex pathways, or airway dysbiosis. SUMMARY/CONCLUSIONS:In bronchiectasis, reflux should be separated into clinically relevant phenotypes, including typical gastroesophageal reflux disease, proximal or nonacid reflux, laryngopharyngeal symptoms, dysphagia, and aspiration. Management should be guided by the suspected reflux or aspiration pattern because acid suppression alone may not address airway-relevant reflux. Future studies should pair objective reflux and swallowing measures with bronchiectasis-specific outcomes.

PURPOSE/OBJECTIVE:Knobloch syndrome is a rare autosomal recessive condition characterized by lack of functional collagen type XVIII (COL18A1), occipital defects, high myopia, and vitreoretinal degeneration. Clinical features, retinal detachment (RD) rates, and role of prophylactic treatment are not well established. The purpose is to 1) report clinical/systemic features, 2) RD rates and 3) the role of prophylactic treatment in a U.S.-based genetically confirmed cohort. DESIGN/METHODS:Retrospective, nonrandomized multi-center case cohort SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Genetically confirmed Knobloch patients from 12 US -based pediatric retina tertiary referral centers MAIN OUTCOMES MEASURES: Baseline characteristics, RD rates, risk of RD with or without a history of prophylactic treatment RESULTS: 72 eyes (36 patients) were included. Mean follow up was 5.2 years. 14 patients (38.9%) were female. Most common systemic features included 1) occipital defects (n=17 (47.2%)), 2) intracranial abnormalities (n=10 (27.8%); polymicrogyria, plagiocephaly, cortical dysplasia, encephalomalacia, periventricular heterotopia), and 3) skin (n=5 (13.9%)); hemangioma, eczema). Mean +/-SE refractive error was - 9.85 (range -20.12 - +7.50). 18 eyes (25.0%) had cataracts, 16 (20.0%) iris defects (transillumination defects, absent crypts, pupillary membrane), 40 (57.1%) optically empty/vitreous condensations, and 64/70 eyes (91.4%) had macular abnormalities ranging from tessellated fundus to generalized macular atrophy.Of 72 eyes, 23 (31.9 %) experienced an RD, 12 (52.2%) at baseline. Two eyes (8.7%) had a concurrent macular hole. Mean age at RD was 6.24 years and time to RD was 18.6 months (0 - 86). 20 eyes (87.0%) underwent RD surgery (laser, SB, PPV, or PPV/SB). Single and final anatomic success was 60% and 85%. 21/72 eyes (29.2%) received laser or scleral buckle prophylaxis - only two of which (9.0%) developed an RD. Age-adjusted GEE logistic model demonstrated lower odds of RD in eyes that received prophylaxis than not (OR 0.20, P = 0.022). 4/19 fellow eyes (21%) developed an RD (n=1 with previous RD prophylaxis). There was a nonsignificant lower odds of RD in fellow eyes that received RD prophylaxis versus no prophylaxis (OR = 0.42, p = 0.41). CONCLUSION/CONCLUSIONS:In genetically confirmed Knobloch, RD rates are high, and RD prophylaxis appeared to reduce risk of RD. Early diagnosis and prophylaxis should be considered in this population.

OBJECTIVE:Mitotane is e first-line medical treatment for adrenocortical carcinoma (ACC). Mitotane has substantial dr awbacks, including severe toxicity and contralateral gland destruction, whilst effective in only 25-30% of ACCs. To improve patient selection for mitotane therapy, this study aimed to identify tissue biomarkers associated with in vitro mitotane response. DESIGN/METHODS:Retrospective cohort study. METHODS:We performed transcriptomic and proteomic analyses on fresh-frozen human ACC tissues classified as responders (n=13), partial responders (n=10), or non-responders (n=7) based on in vitro mitotane-induced inhibition of cell proliferation. RESULTS:Responders showed distinct transcriptomic and proteomic signatures compared with partial and non-responders, whereas fewer differences were found between the latter groups. Integrating transcriptomic and clinicopathological data indicated that responders frequently had cortisol-producing ACC with metastases or nodal involvement. Furthermore, their transcriptomes aligned with aggressive, proliferative ACC subtypes described previously. Differential expression analysis identified 718 genes and 60 proteins that distinguished responders from non-responders. Pathway and network analyses revealed upregulation of cell cycle and collagen related genes and downregulation of mitochondria related genes and proteins in responders. CONCLUSIONS:In summary, transcriptomic and proteomic profiling offers promise to predict mitotane response in ACC. Our findings suggest that responders exhibit features of aggressive ACC, with distinct molecular characteristics that could serve as biomarkers for treatment selection.

BACKGROUND:Cannabis use among older adults has increased in recent years. Age-related physiological changes, socio-ecological factors, and medications may exacerbate potential adverse effects of cannabis and complicate the detection of cannabis use disorder (CUD) in older adults. However, current estimates of cannabis use are largely limited to national surveys, which may have age-related surveying challenges. METHODS:We conducted an intercept survey of 315 adults aged ≥ 65 in New York City, primarily in public parks and immediately outside older adult centers. The survey asked primarily about drug use with a focus on past-year cannabis use, reasons for use, adverse effects, and CUD. We examined reported cannabis use and delineated correlates of use and of having CUD. RESULTS:22.2% of participants (n = 70) reported past-year cannabis use, and among them, 11.1% (n = 35) reported past 24-h use. Older [adjusted odds ratio (aOR) = 0.90, 95% CI: 0.84-0.95] and female participants were at lower odds for use (aOR = 0.35, 95% CI: 0.17-0.73), and those who smoked cigarettes were at higher odds (aOR = 3.73, 95% CI: 1.65-8.48). Cannabis was most often used to get high (60.0%), relieve tension (55.7%), sleep (52.9%), or relieve chronic pain (30.0%). Dry mouth (41.4%) and drowsiness (18.6%) were the most reported adverse effects. Nearly a third (32.9%) who used cannabis had CUD, with 5.7% having severe CUD. CONCLUSIONS:Findings suggest that cannabis use among older adults may be more common and clinically significant than suggested by prior evidence. Improved screening, clinician education, and harm reduction strategies are needed to confront emerging risks in this population.

BACKGROUND:Community-engaged dissemination and implementation research focuses on the implementation of evidence-based interventions within clinical or community-based settings. It uses community-engaged processes or partnerships. This includes (but is not limited to) community-based participatory research (CBPR). CBPR is an approach that centers actively engaging and collaboratively sharing power with community members, which can increase the value of studies for the communities being served and researchers. Community members include those who are most affected by the research (e.g. patients, citizens) and those most invested in the communities being researched (e.g. advocates, leaders). MAIN BODY/METHODS:Policy implementation research is the subfield of implementation science that aims to understand how policies are implemented and improve their implementation. Previous literature discusses policy co-design, defined as actively partnering with community members in the policy making process. In this article, we suggest ways to integrate CBPR methods within policy implementation research as well. We specifically discuss ways that community-members can be actively and substantively engaged in policy implementation in addition to policy making. CONCLUSION/CONCLUSIONS:Policy implementation research researchers who wish to approach their work through a CBPR lens would benefit from our overarching recommendation to meaningfully engage community members throughout the policy implementation research process including (i) building or maintaining meaningful partnerships, (ii) engaging in transparent and equitable resource sharing, cost charging, compensation, and incentives. (iii) co-designing/co-conceptualizing projects, (iv) co-refining the project and co-selecting strategies for project completion, (v) bi-directional learning and open channels of communication during the project period, and (vi) taking action on harmful or inequitable policy implementation research and results of research. We argue that if policies are causing harm or not reaching marginalized communities, researchers should alert policymakers, frontline staff, and community members to this information and actively assist in providing solutions to this issue. Ideally, the steps outlined in this article will enable researchers to directly uncover the presence of harm and/or lack of reach of policies and form the communication channels that would enable researchers to inform policymakers and community members.

Health literacy is a foundational component of providing accessible pediatric care, influencing whether families can understand, access, and use health information. As families increasingly rely on online health resources, health literacy skills applied to digital information, or e-health literacy, has become an evolving dimension of pediatric health literacy. The concept of health literacy extends beyond an individual's abilities, intersecting with the demands placed on individuals by healthcare systems. There is a growing focus on organizational health literacy (OHL), which reflects how effectively systems support equitable communication, but this remains infrequently assessed or implemented. Limited parent, child, and adolescent health literacy is common and disproportionately affects families with lower income, minoritized racial/ethnic backgrounds, lower educational attainment, and who use languages other than English for care. Limited health literacy has been associated with decreased disease-specific knowledge, suboptimal health behaviors, and worse clinical outcomes. Although health literacy-informed strategies can improve comprehension and outcomes, best practices, such as teach-back, remain underutilized across pediatric care settings. The rapid expansion of digital tools offers new opportunities to enhance health literacy-informed communication but also introduces challenges related to equity, accuracy, and safety. Advancing pediatric health literacy requires coordinated efforts: embedding health literacy principles into institutional and national policies, integrating universal health literacy precautions into clinical workflows, expanding clinician and patient health literacy education, and advancing health literacy-focused research, including on digital interventions and artificial intelligence (AI)-supported communication. Prioritizing these efforts is essential to creating health literate-systems that enable all families to access, understand and use health information.

How can theory and mathematical modeling help accelerate research in psychiatry? Here we highlight the promise of computational approaches via three recent trends: multi-scale models of working memory which link receptors and cell-types to brain-wide activity and behavior; the extension of mechanistic computational models from working memory to other cognitive functions including conscious perception, attention and planning; and cross-species comparative models of cognition that give rise to translational computational neuroscience. These developments demonstrate the feasibility of achieving understanding across spatial and biological scales in psychiatry research. Crucially, computational findings now can give rise to specific and testable mechanistic hypotheses for a wider range of symptoms associated with mental disorders. Finally, computational tools have emerged to guide translational neuroscience towards the experiments that are most likely to translate to treatment of human brain disease. We provide primer coding notebooks for several models to accompany the article.