Faculty Bibliography

INTRODUCTION/UNASSIGNED:Cognition is influenced by the neighborhood social and built environment, but the underlying mechanisms through which neighborhood environments affect cognition are unclear and may differ by race/ethnicity. The authors tested the hypothesis that sleep mediates the association between environmental characteristics and cognition. The authors also explored environment-sleep-cognition interrelationships separately for non-Hispanic White, non-Hispanic Black, and Hispanic older adults in the U.S. METHODS/UNASSIGNED:Analyses included older adults from Round 2 of the National Social Life, Health, and Aging Project (N=3,111). The social environment latent variable was constructed using indicators for social cohesion, social ties, and perceived neighborhood danger. The built environment was operationalized using indicators for litter, noise, traffic, pollution, and building conditions. Gross cognitive ability was characterized using the Chicago Cognitive Function Measure as an estimate of Montreal Cognitive Assessment scores. Actigraphic sleep characteristics included sleep fragmentation, time spent awake after sleep onset, and sleep percentage. RESULTS/UNASSIGNED:Participants with better cognition lived in supportive social environments and less hazardous, disruptive (e.g., noisy, polluted) built environments. The sleep mediation hypothesis was partially supported in the full sample: time spent awake after sleep onset mediated the social environment-cognition relationship, but sleep characteristics did not mediate the built environment-cognition relationship. However, in exploratory subgroup analyses, sleep mediated the social environment-cognition relationship among White older adults and mediated the built environment-cognition relationship among Black older adults. Sleep did not mediate any environment-cognition relationships among Hispanic older adults. CONCLUSIONS/UNASSIGNED:These results demonstrate that although the social and built environment influence cognition directly and indirectly through sleep, the mediational pathways may vary by specific racial/ethnic subgroups.

Talimogene laherparepvec (T-VEC), the first FDA-approved oncolytic viral therapy, has transformed cancer immunotherapy since its 2015 approval for unresectable melanoma. Engineered from Herpes Simplex Virus type 1 (HSV-1) with deletions in ICP34.5 and ICP47 genes and GM-CSF insertion, T-VEC selectively replicates within the tumor cells, inducing lysis and releasing tumor-derived antigens while stimulating systemic antitumor immunity through dendritic cell activation. Although extensively studied for melanoma, its potential extends beyond this malignancy, with emerging applications in breast cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), and other solid tumors. This review synthesizes T-VEC's mechanism of action, leveraging dysregulated Ras signalling, impaired interferon pathways in cancer cells, its clinical outcomes, and safety profile across these indications. While prior literature emphasizes melanoma monotherapy and combinations with immune checkpoint inhibitors, less attention has been given to its efficacy in non-melanoma cancers and synergistic potential with chemotherapy or radiation therapy. By exploring recent trials, such as T-VEC with neoadjuvant chemotherapy in triple-negative breast cancer and pembrolizumab in HNSCC, highlighting its versatility. Comparative analysis with other oncolytic viruses like HF-10, oncorine (H101), and measles virus variants positions T-VEC within the virotherapy landscape. Key challenges-systemic delivery, immune clearance, and biomarker development for patient selection-are addressed alongside strategies to enhance immune modulation through novel combinations. This review underscores T-VEC's expanding role in cancer treatment, offering clinicians' and researchers' insights to optimize its therapeutic horizons across diverse malignancies.

This phase 2 study evaluated the efficacy and safety of combining acalabrutinib (A) and lenalidomide (L) with either rituximab (ALR) or obinutuzumab (ALO), with longitudinal minimal residual disease (MRD) monitoring in frontline MCL treatment (ClinicalTrials.gov - NCT03863184). The primary objective was molecular CR after 12 cycles of induction, defined by Lugano criteria and undetectable MRD <10-6 (uMRD6) by clonoSEQ. Secondary objectives included safety, responses and survival. Exploratory objectives included tumor mutation profiles and cell-free DNA (cfDNA) by CAPP-Seq. Patients in uMRD6 molecular CR were eligible for discontinuation of A+L after 24 cycles; all patients received a minimum of 36 cycles of anti-CD20 antibody treatment. In the ALR cohort, grade 3-4 hematologic toxicities included neutropenia (38%), thrombocytopenia (4%) and anemia (4%). Non-hematologic toxicities included rash (42%), fatigue (4%), nausea (4%), and vomiting (4%). The ORR was 100%, CR 83% and molecular CR 67% after 12 cycles of induction, with best molecular CR at 83%. At a median follow-up of 53 months (range 46-60), the 4-yr OS and PFS for ALR were 91% and 76%, respectively. TP53 mutations were adversely associated with PFS (p=0.026). For ALO, ORR, CR and molecular CR were 90% following induction, and 2-yr OS and PFS were both at 100%. Longitudinal cfDNA analysis in ALR revealed clonal evolution during response and progression. This safe and active regimen is feasible as a time-limited initial therapy for MCL patients and warrants further evaluation in response-adapted strategy.

INTRODUCTION/BACKGROUND:Redo hypospadias repairs present significant challenges due to tissue scarring and hypovascularity, substantially increasing the risk of complications. Previous literature document complication rates above 40 % after three or more previous urethroplasties, highlighting the need for strategies that enhance tissue quality. Postoperative hyperbaric oxygen therapy (HBOT) can improve healing outcomes. However, the role of perioperative HBOT in enhancing tissue quality through neovascularization remains unclear. This study aims to evaluate whether perioperative HBOT (both pre- and postoperative) instead of the senior author's standard of care (SOC) topical nitroglycerin reduces complication rates and improves surgical outcomes in redo hypospadias repair. METHODS:We retrospectively reviewed 47 patients (aged 3-18 years) who underwent redo hypospadias repairs between January 2019 and January 2022, following 2-4 prior failed procedures. Inclusion criteria included patients with failed primary repairs, while exclusion criteria included patients with contraindications to HBOT or incomplete follow-up data. Patients were allocated to treatment groups (i.e. perioperative HBOT v. SOC) based on insurance coverage for HBOT rather than randomization. Group 1 (n = 31) received perioperative HBOT while Group 2 (n = 16) received SOC, consisting of topical nitroglycerin ointment. Additionally, BMG patients in both groups received topical vitamin E for 2-3 weeks post-operatively. HBOT protocol consisted of 20 preoperative sessions and 5-10 postoperative sessions at 2.0 ATA. RESULTS:The two groups did not differ significantly in hypospadias locations (Group 1: 22 distal, 9 proximal; Group 2: 10 distal, 6 proximal; P = 0.795) or operative technique (Group 1: 21 one-stage dorsal inlay grafts [DIG], 10 staged buccal mucosa grafts [BMG]; Group 2: 10 one-stage DIG, 6 staged BMG; P = 0.972). The HBOT group demonstrated a reduction in postoperative complications compared to SOC group (6.4 % vs. 25 %; P = 0.179 95 % CI 0.05-1.26), though this difference did not reach the level of statistical significance. Specifically, the HBOT group experienced only two cases of fistula formation, while the SOC group had four total complications: one case of graft contracture and three fistulas. All complications were successfully corrected surgically one year postoperatively using the perioperative HBOT protocol. Subjective clinical assessment also suggested improved tissue quality and pliability in HBOT-treated patients. CONCLUSIONS:This study suggests that perioperative HBOT was associated with a lower, but not statistically significant, complication rate in redo hypospadias repairs. The findings support the potential use of perioperative HBOT in promoting tissue healing and justify further investigation through prospective randomized controlled trials to establish definitive efficacy and optimize treatment protocols for this challenging patient population.

BACKGROUND:Characterising disparities in HIV infection across populations by gender, age, and HIV risk is key information to guide intervention priorities. We aimed to assess how indicators measuring HIV acquisitions, transmissions, or potential long-term infections influence estimates of the contribution of different populations to new infections, including key populations (including female sex workers, their clients, men who have sex with men). METHODS:) measured the proportion of new infections averted if transmission involving a specific population was blocked over a specific time period. We compared estimates of the four indicators across seven populations and 15 settings and assessed if the contribution of specific populations ranked differently across indicators for ten settings. FINDINGS/RESULTS:), whereas more infections were transmitted than acquired in non-key population men aged 25 years and older (median 1·4 times more) and clients of female sex workers (1·6 times more) in all but one model. Estimates of the 10-year tPAFs accounting for transmission in the long-term were substantially larger than the direct transmission indicator for all populations, especially for female sex workers (2·0 times higher). INTERPRETATION/CONCLUSIONS:Indicators that reflect HIV acquisitions and transmissions in the short and long term can be used to capture the complexity of HIV epidemics across different populations and timeframes. The added nuance would improve the effectiveness of the HIV prevention response across all populations at risk. FUNDING/BACKGROUND:US National Institutes of Health and UK Medical Research Council. TRANSLATION/UNASSIGNED:For the French translation of the abstract see Supplementary Materials section.

BACKGROUND:Positive psychology well-being constructs like flourishing are important predictors of health and quality of life. However, few studies have examined the association between flourishing and psychological distress (i.e., depression and anxiety). We investigated the association between flourishing and psychological distress symptoms among higher education students. METHODS:We analyzed cross-sectional survey data from 60,386 students aged 18-34 in the United States (Healthy Minds Study 2022-2023). Flourishing was measured using the Flourishing Scale, while symptoms of depression and anxiety were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 scales, respectively. Associations between flourishing and psychological distress were examined using multiple logistic regression models, adjusting for age, gender identity, race/ethnicity, financial stress, and self-reported mental health treatment. RESULTS:Of the 60,386 participants included the mean age was 21.7 (SD = 3.6). Most participants were female (68.3 %) and White (55.6 %). Among individuals with significant symptoms of depression or anxiety, 13.7 % and 17.7 % were classified as flourishing (Flourishing Scale ≥48), respectively. Participants with significant symptoms of depression (OR: 0.23; CI: 0.22-0.25) or anxiety (OR: 0.56; CI: 0.54-0.59) were less likely to be classified as flourishing than those without significant symptoms. CONCLUSION/CONCLUSIONS:Flourishing is possible within psychological distress. These results suggest the importance of assessing both positive psychological well-being and psychological distress to understand student mental health. While reducing symptoms of psychological distress is crucial, enhancing positive psychological well-being should also be prioritized as part of mental health treatment.

Obstructed hemivagina and ipsilateral renal anomaly is a Mullerian anomaly with variable presentations. A patient with this syndrome had a superinfected fluid collection in an obstructed hemivagina after mifepristone and misoprostol administration for an embryonic demise, identifying a potential complication in this population.

Obesity constitutes a substantial burden in psoriatic disease that affects approximately half of patients. Importantly, increased adiposity and psoriatic disease are strongly linked, with obesity functioning as both a possible trigger and a disease modifier. Obesity predisposes individuals to develop psoriasis and is likely to drive, at least partially, the progression from psoriasis to psoriatic arthritis. For people with psoriasis or psoriatic arthritis, obesity is associated with lower rates of remission and poorer responses to treatment. Several mechanisms probably underlie this relationship, including systemic and local pro-inflammatory properties of adipose tissue, increased biomechanical stress on joints and entheses, gut dysbiosis and synergistic effects of osteoarthritis. Notably, weight loss can improve both psoriatic disease course and response to therapy; however, current approaches (such as dietary interventions or bariatric surgery) are difficult to implement. Glucagon-like peptide-1-based therapies are an effective strategy for weight loss in psoriatic disease and might even have additive disease-modifying effects to conventional immunomodulators. Although often overlooked, weight loss intervention and obesity management should be included as an integral part of psoriatic disease treatment algorithms.

Chronic total occlusion percutaneous coronary intervention (CTO-PCI) is a complex, high-radiation procedure that requires careful radiation management to protect both patients and health care providers. This review outlines the biological risks of radiation exposure, differentiating deterministic and stochastic effects, and highlights key safety thresholds and regulatory guidelines. It presents a range of mitigation strategies across procedural phases, including advanced shielding systems, low-dose imaging platforms, and real-time monitoring tools. Institutional protocols and a culture of shared accountability are emphasized to support the ALARA principle. Emerging technologies offer promising solutions to reduce operator exposure and improve safety outcomes in modern CTO-PCI practice.