Faculty Bibliography

PURPOSE/OBJECTIVE:Obesity is increasingly encountered among patients requiring extracorporeal membrane oxygenation (ECMO) for severe respiratory or cardiac failure. It alters respiratory and cardiovascular physiology and drug pharmacokinetics and introduces technical and logistical challenges that may complicate patient selection, ECMO initiation, cannulation, anticoagulation, and monitoring. This review summarizes current evidence regarding the epidemiology, physiological implications, outcomes, and management of obesity in patients supported with veno-venous (VV) or veno-arterial (VA) ECMO. RESULTS:Available evidence, largely retrospective and based on body mass index classifications, suggests that obesity should not be considered a contraindication to VV-ECMO, with outcomes comparable to or potentially better than those of patients without obesity. However, obesity-related respiratory mechanics may exaggerate the apparent severity of lung injury, emphasizing the need for optimized conventional ARDS management, including appropriate ventilatory strategies and prone positioning, before ECMO initiation. In contrast, outcomes during VA-ECMO are more heterogeneous, particularly in extracorporeal cardiopulmonary resuscitation (ECPR), and may be influenced by patient selection, comorbidities, and timing of support. Obesity also creates important technical challenges requiring individualized cannulation, anticoagulation, and perfusion strategies. CONCLUSION/CONCLUSIONS:Obesity alone should not preclude access to ECMO, particularly VV-ECMO. Successful management requires anticipation of obesity-related challenges, appropriate infrastructure, and structured multidisciplinary protocols. Further prospective studies are needed to clarify obesity-specific risks, optimize management strategies, and evaluate long-term outcomes.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Compartmentalized CNS inflammation involving B cells is implicated in gray matter injury and disease progression in multiple sclerosis (MS). Products secreted by B cells of patients with MS can kill oligodendrocytes and neurons, a cytotoxicity conferred by their exosome-enriched extracellular vesicle (Ex En) fraction. METHODS:To explore the potential molecular mediators of this cytotoxicity, we profiled proteomic and transcriptomic cargo of Ex En isolated from B cells of patients with treatment-naive MS and matched healthy controls. RESULTS:MS B-cell-derived Ex En appeared enriched in cell-death-associated proteins (including fibrinogen, complement C9, APP, and SPARC) and deficient in cell-survival-associated proteins (such as galectin-3). Abnormal enrichment for cell-death proteins was supported by gene set enrichment analysis. Protein pathway analysis revealed densely connected prodeath modules in the MS B-cell-derived Ex En, contrasting with homeostatic signatures in controls. Transcriptomic analysis further revealed that Ex En of MS B cells appeared to carry reduced levels of miRNAs (miR-182, miR-212, and miR-1270) known to inhibit apoptosis. DISCUSSION/CONCLUSIONS:Our findings indicate that B-cell-derived Ex En of patients with MS, previously shown to impair neuronal and glial survival, harbor an abnormal cytotoxic molecular profile that may contribute to CNS-compartmentalized injury and progressive MS biology.

BACKGROUND:Patient experience is a key component of care quality, linked to outcomes like safety and medication adherence. In high-acuity inpatient settings with rotating teams, opportunities exist to better integrate patients' identities and values into the hospital experience. AIM/OBJECTIVE:To design, implement, and evaluate an EHR-integrated tool that enables hospitalized patients to share personal, non-medical information to help care teams deliver more personalized care. SETTING/METHODS:Fourteen adult inpatient units across a large academic medical center (NYU Langone Health, New York, NY). PARTICIPANTS/METHODS:Hospitalized adults and their interprofessional care teams, including physicians, nurses, advanced practice providers, and allied health professionals. PROGRAM DESCRIPTION/METHODS:About Me is an Epic-integrated digital tool that allows patients or caregivers to share brief, non-clinical details-such as hobbies, values, family, and communication preferences-visible to the entire care team. Patients complete entries via the NYU Langone Health App or with nurse assistance; nurses validate content for appropriateness. PROGRAM EVALUATION/RESULTS:Over a 2-month period, 1001 of 5452 eligible patients (18.4%) submitted entries. Entries were brief but meaningful. Five major themes emerged: hobbies, family, identity, career, and animals. DISCUSSION/CONCLUSIONS:Implementation of About Me was feasible and acceptable. Even brief entries offered meaningful context that may strengthen rapport and promote more personalized, compassionate inpatient care.

PURPOSE/UNASSIGNED:Breast carcinoma is the most commonly diagnosed cancer worldwide and represents the most common primary tumor metastasizing to the orbit. Herein, we present the largest review of the clinical features of orbital metastases from breast carcinoma reported in the literature and describe four additional patients. METHODS/UNASSIGNED:Case reports and case series of biopsy-proven orbital metastases from breast carcinoma published between 2011 and 2025 were identified through a MEDLINE search. Of 220 records screened, 63 articles (29%) met inclusion criteria. Titles, abstracts, and full texts were reviewed for eligibility. Data extracted included patient demographics, tumor subtype and receptor status, timing of breast cancer diagnosis relative to orbital presentation, clinical features, imaging findings, treatments, and survival outcomes. RESULTS/UNASSIGNED:Sixty-nine cases of breast carcinoma metastatic to the orbit from 63 articles were reviewed. The majority of patients were female (66 of 69, 96%). The average age at presentation of orbital symptoms was 60 years. Orbital metastasis was the presenting manifestation of breast cancer in 30/69 patients (43%). In 15 of 69 patients (22%), orbital metastasis was initially diagnosed as a different orbital process. Among the 49 patients for whom primary tumor type was reported, 25 of 49 (51%) had lobular carcinoma and 21 of 49 (43%) had ductal carcinoma. Two patients had independent lobular and ductal primaries, and one patient had a phyllodes tumor. The most common presenting orbital signs or symptoms were diplopia and/or limited motility (45 of 69, 65%) and decreased or blurry vision (33 of 69, 48%). Treatment of the primary breast carcinoma with orbital metastases varied widely and changed over time with near-equal representation of chemotherapy, hormonal therapy, and radiation therapy. Documentation of survival time was inconsistent. CONCLUSIONS/UNASSIGNED:Breast carcinoma, including metastatic disease, is increasingly characterized by improved survival and prolonged disease control in selected patients with advances in systemic therapy. In patients with a history of breast cancer, metastatic disease should be considered in those presenting with orbital pathology. Conversely, unexplained orbital findings may warrant evaluation for occult malignancy.

BACKGROUND/UNASSIGNED:Nontuberculous mycobacteria pulmonary disease (NTM PD) has been increasing in the United States, and New York City is an important hotspot, with a high burden of disease. RESEARCH QUESTION/UNASSIGNED:We assessed how neighborhood-level risk factors influenced NTM PD prevalence in New York City. STUDY DESIGN AND METHODS/UNASSIGNED:We used outpatient claims data from hospitals participating in the Patient-Centered Outcomes Research Institute network, compiled by the INSIGHT Clinical Research Network at Weill Cornell Medicine. NTM PD period prevalence (referred to here as 'prevalence') was estimated by New York City neighborhood for the study period 2012 through 2022. A case was defined as someone with at least one claim for NTM PD. De-identified NTM PD case data and demographic data were analyzed by neighborhood of residence at diagnosis. Using prevalence estimates, we detected high- and low-prevalence regions within New York City and associated these estimates with demographic, clinical, socioeconomic, and environmental neighborhood-level factors using Poisson regression and backward elimination of covariates. RESULTS/UNASSIGNED:Overall, 6,169 NTM PD cases were identified among persons receiving care across 17 private New York City hospitals. The mean age was 67.5 years, 68.7% were female, and 57.3% were White. Over the study period, NTM PD prevalence increased throughout New York City, and median year built of housing units, median income, and median age of residents were significant neighborhood-level risk factors. The highest prevalence neighborhoods were in Manhattan, while the lowest prevalence neighborhoods were in Brooklyn and Staten Island. INTERPRETATION/UNASSIGNED:Our findings indicate that neighborhood-level access to care may explain the heterogeneity in NTM PD prevalence among New York City neighborhoods, as higher income, newer neighborhoods exhibited the highest NTM PD prevalences. Future studies should examine the extent of undetected NTM PD in New York City, particularly in low-income areas.

SUMMARY/CONCLUSIONS:Association measurements, such as mutual information (MI), are fundamental in the analysis of cancer multi-omics data for identifying cancer-related genes, gene signatures, and gene regulatory networks, thereby shedding light on tumor development, progression, and treatment. Confounding factors, including tumor purity and mutation burden, can bias association measurements in MI, potentially leading to the misclassification of passenger events as drivers. Conditional mutual information (CMI) provides a robust framework for assessing both linear and nonlinear associations while effectively accounting for different confounding factors. An R package called conMItion is introduced to estimate CMI and its statistical significance for multi-omics data, with the flexibility to adjust for one or two confounding factors. We demonstrated the utilization of conMItion through two use cases. First, we identified interchromosomal somatic copy number alteration-expression associations in bladder cancer. Second, we identified associated cell types within the lung cancer tumor microenvironment using single-cell RNA sequencing datasets. AVAILABILITY AND IMPLEMENTATION/METHODS:The conMItion package is freely available on CRAN at https://CRAN.R-project.org/package=conMItion. The two use cases described in the paper can be accessed at https://github.com/GJYWang/conMItion. A supplementary document is available online.

PURPOSE/OBJECTIVE:The dependence of the long-time (tortuosity) limit of the extra-cellular diffusivity on the intra-cellular volume fraction is of fundamental importance for microstructure modeling. While such dependencies have been explored for the white matter, the tortuosity limit in gray matter is unknown due to complex cell composition and geometry. Here we rationalize and validate numerically the analytical relation between the extra-cellular diffusivity and intra-cellular fractions of cell bodies (somas) and neurites. METHODS:The tortuosity relation for extra-cellular diffusivity qualitatively follows from effective medium theory, coarse-grained by diffusion outside somas (spheres) and neurites (cylinders), respectively. This problem is equivalent to finding the overall conductivity in a medium of grains in a matrix, with methodology dating back to the 19th century. We extend the effective medium methodology to populations of impermeable spheres and randomly oriented cylinders with various volume fractions, yielding closed-form expressions corroborated by Monte Carlo simulations. RESULTS:We establish the power-law scaling of the extra-cellular diffusivity with the volume fractions of the extra-soma and extra-neurite spaces. We further evaluate the proposed framework using simulations in realistic tissue geometries, and by applying it to in vivo MRI data. CONCLUSION/CONCLUSIONS:Theory and simulations relate extra-cellular tortuosity to soma and neurite fractions, thereby offering a diffusion MRI protocol design optimized for in vivo assessment of soma size and soma/neurite fractions within clinical scan times. Such in vivo measurements can be used to study development, aging, and neurodegenerative disorders.

PURPOSE/UNASSIGNED:Excimer laser therapy, a 308-nm narrowband UV-B modality, has shown promise in inflammatory dermatoses, but remains understudied in scarring alopecia (SA). MATERIALS AND METHODS/UNASSIGNED:We conducted an IRB-approved retrospective study of adults with SA treated with excimer therapy to characterize clinical outcomes, response timelines, and treatment patterns. RESULTS/UNASSIGNED:. After a mean of 3.4 months, 60% of patients reported subjective improvement in hair or hairline appearance. Symptomatic improvements were observed in scalp pain (100%), burning (75%), and pruritus (50%), generally within two to six months. Signs of inflammation, including perifollicular hyperkeratosis and erythema, improved in 83% of affected patients. Trichoscopic measures of hair density and shaft caliber remained stable, suggesting disease stabilization without accelerated follicular loss. Adverse effects were common but mild, including erythema, burning, and pain, and did not lead to koebnerization. CONCLUSIONS/UNASSIGNED:Overall, excimer therapy was well-tolerated and associated with meaningful clinical and symptomatic improvement. These findings support excimer therapy as a potentially effective adjunctive treatment for inflammatory control and stabilization in SA, with response typically occurring within the first several months of therapy.