Faculty Bibliography

The immune system is tasked with mounting effective responses to pathogens while preventing inflammation triggered by innocuous antigens, including those derived from self, food, and commensal microbes. This balance is especially critical in the intestine, where dietary and microbial antigens are constantly encountered. Peripherally induced regulatory T cells (pTreg or iTreg) play a key role in suppressing inappropriate immune activation and maintaining gut homeostasis. Elucidating how pTreg cells are generated along the gastrointestinal tract is therefore critical to understanding peripheral tolerance. Recent studies have revealed that intestinal antigen-specific pTreg cell differentiation is induced by a distinct lineage of antigen-presenting cells (APCs) requiring expression of the transcription factors RORγt and PRDM16. Genetic perturbation of these APCs results not only in microbiota-specific proinflammatory T cell responses but also in the breakdown of oral tolerance, which in turn predisposes to allergic inflammation. In this review, we summarize the discovery of these tolerance-inducing APCs, highlight their role in instructing pTreg cell differentiation in response to microbiota and dietary antigens, and discuss the regulatory networks that support their function during intestinal immune tolerance.

IMPORTANCE/UNASSIGNED:The current ocular Common Terminology Criteria for Adverse Events (CTCAE) mix eye signs with symptoms and lack standardized clinical photographs and experimental oncology drug dose modification recommendations. Robust reporting of ocular adverse events (AEs) is important to maintain patient safety and to guide the development of novel efficacious drugs. OBJECTIVE/UNASSIGNED:To develop improved ocular AE grading scales to reliably evaluate and grade ocular AEs in patients on experimental oncology drug therapy and to provide clear drug dose modification recommendations. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A collaborative multicenter interspecialty working group consisting of oncologists and academic ophthalmologists from 11 academic centers in the US and ophthalmologists from the US Food and Drug Administration was assembled in February 2023 to form a consensus on new experimental oncology drug-related ocular AE grading scales. The grading scales were released in June 2023. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Expert consensus on novel experimental oncology drug-related ocular AE grading scales. RESULTS/UNASSIGNED:Six experimental oncology drug-related ocular AE grading scales were developed with agreement from ophthalmologists and oncologists for use in antibody-drug conjugate clinical trials: visual acuity, eye symptoms, cornea, conjunctiva/sclera, anterior chamber, and retina/posterior segment. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The new experimental oncology drug-related ocular AE grading scales developed by the consensus panel were developed to be more concise, containing photographs where applicable, and to provide clear drug dose modification recommendations compared with the previous CTCAE. Use of these ocular AE grading scales may allow for more objective and consistent incidence measurements of ocular AEs throughout clinical trials and postmarketing, potentially facilitating safe testing of novel agents that may cause eye toxicity.

BACKGROUND:Bariatric surgery has long been established as an effective treatment option for obesity and diabetes [Kalainov et al. in J Am Acad Orthop Surg [32(10):427-438, 2025] and Ogden et al. in JAMA 311(8):806-806, 2025. 10.1001/jama.2014.732]. Recently, GLP-1 Receptor Agonists' (GLP-1RAs) use has expanded as an alternative therapy for weight loss and diabetes management. While GLP1RAs are known to be safe and effective, few have compared long term outcomes of GLP-1RAs versus the "gold standard" of bariatric surgery among Medicare/Medicaid patients, who make up the largest payer group in the U.S. [Kalainov et al. in J Am Acad Orthop Surg [32(10):427-438, 2025]. METHODS:This was a retrospective, multicenter study of obese, type-2 diabetic patients (T2D) ≥ 18 years old, who initiated weekly injectable semaglutide or tirzepatide or underwent bariatric surgery between January 1st, 2018 to July 31st, 2024. Patients with a baseline BMI ≤ 35, those with prior GLP1-RA use, or any prior bariatric procedure were excluded from analysis. The primary outcome of interest was % total body weight loss 3 months to 3 years post intervention among bariatrics surgery patients vs. GLP1-RA patients (any GLP1-RA prescription and 12 months continuous GLP1-RA prescription). RESULTS:7667 patients were included for analysis (7200 GLP1-RA, 467 bariatric surgery). Bariatric surgery patients were younger (median (IQR): 43 (34, 53) vs. 65 (54, 72); p < 0.001) and more likely to be female (67.5% vs. 60.8%; p < 0.01) and Hispanic (58.7% vs. 19.4%; p < 0.001) while GLP1-RA users were more likely to be white (58.5% vs. 10.7%; p < 0.001). In models adjusting for demographic and clinical characteristics, bariatric surgery was associated with a 22.9% total weight loss 3 years following surgery compared to 2.3% for patients with any GLP1-RA use, and 15.9% vs 2.4% for patients with 12 months consecutive GLP1-RA use (22.9 [21.0-24.8] vs 2.3 [0.5-4.1], 15.9 [6.9-24.9] vs. 2.4 [6.7-11.5]. CONCLUSIONS:Among obese, T2D, publicly insured patients, bariatric surgery was associated with greater weight loss than GLP1-RAs at all measured periods from 3 months to 3 years post op.

PURPOSE/OBJECTIVE:To introduce mtrk, a new open-source tool based on modern software-engineering principles that simplifies pulse-sequence design, implementation, and dissemination. METHODS:The mtrk framework is vendor-agnostic and relies on a compact and human-readable descriptive language. Users can design pulse sequences using either a Python-based programming interface or an intuitive graphical interface. The graphical interface also allows for visualizing pulse-sequence diagrams. A driver sequence was developed to run mtrk sequences on MR scanners. A spin-echo sequence was designed with mtrk and converted to Pulseq for comparison. Both versions were compared to an equivalent vendor sequence in phantom and in vivo experiments. RESULTS:Images from the mtrk and Pulseq versions were nearly identical and showed over 90% similarity compared to the vendor sequence, despite minor unavoidable design differences. Phantom images matched corresponding synthetic images simulated using the same pulse sequences. CONCLUSION/CONCLUSIONS:The mtrk framework simplifies the development of pulse sequences by providing an intuitive descriptive language and compatibility with the Pulseq format. Users can design and simulate pulse sequences using the graphical interface without any programming experience.

BACKGROUND:Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder marked by fibrofatty myocardial replacement, leading to ventricular dysfunction and life-threatening arrhythmias. Historically identified as a right ventricular disease, advances in cardiac magnetic resonance imaging (CMR) have revealed left ventricular involvement in some cases, underscoring the need for refined diagnostic criteria. Conventional echocardiographic methods lack sensitivity, particularly for early disease detection, while strain imaging holds promise for identifying subclinical dysfunction. OBJECTIVE:This review explores the advancements in echocardiographic strain imaging techniques for ACM diagnosis and prognosis, focusing on recent developments in right and left ventricular assessment, differentiation from athletic remodeling, and integration with CMR findings. METHODS:An extensive review of contemporary literature was conducted, analyzing diagnostic thresholds, prognostic significance, and the utility of echocardiographic strain imaging compared to standard measures. FINDINGS/RESULTS:Echocardiographic right ventricular strain assessment offers enhanced diagnostic sensitivity, identifying ACM in cases that fail to meet traditional echocardiographic criteria. Strain provides superior prognostic discrimination, correlating with risk of ventricular arrhythmias and disease progression. Left ventricular strain, particularly global longitudinal strain (GLS), detects subclinical dysfunction and predicts adverse outcomes, emphasizing its importance in left-dominant ACM phenotypes. Strain-based mechanical dispersion metrics also facilitate early disease detection and risk stratification. CONCLUSION/CONCLUSIONS:Echocardiographic strain imaging is a valuable, non-invasive tool for ACM, addressing gaps in traditional echocardiographic diagnostic criteria. Standardization of thresholds and broader integration into clinical practice are required to maximize its utility. Future directions include leveraging machine learning and multimodal imaging for comprehensive ACM characterization.

OBJECTIVE:NF2-related schwannomatosis (NF2-SWN) is an autosomal dominant genetic disorder characterized by the development of schwannomas, meningiomas, and spinal ependymomas. Treatment with bevacizumab, a monoclonal antibody against VEGF, has been shown to result in decreased vestibular schwannoma size and hearing improvement in ~50% of NF2-SWN patients. It is unknown whether the same degree of benefit is seen in younger patients compared with older patients. The objective of this study is to determine the association between age and bevacizumab treatment outcomes in NF2-SWN. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Thirty-seven patients with NF2-SWN. INTERVENTIONS/METHODS:Bevacizumab. MAIN OUTCOME MEASURES/METHODS:Change in tumor size of 20% or more. RESULTS:This study includes 37 patients with NF2-SWN who were treated with bevacizumab at our institution between 2014 and 2024. They were divided into 2 groups: 22 adults over the age of 25 (26 to 71 y) and 15 adolescent and young adult (AYA) patients under the age of 25 (12 to 24 y). The median treatment duration was 2.1 years. A significantly higher proportion of AYA schwannomas (37.5%, n=9) exhibited radiographic tumor progression during the treatment period compared with those of the older patient group (11.9%, n=5) (P=0.026), despite similar pre-treatment growth rates. There was no significant difference in the proportion of older and younger patients with hearing decline, improvement, or stability (P>0.05). CONCLUSIONS:AYA patients were significantly more likely to exhibit progression of tumor growth during bevacizumab treatment compared with older patients, though no significant differences were detected in hearing outcomes.

In this retrospective cohort study of 5,690 adults ≥ 65 years with non-traumatic corneal perforations, Black and older patients were less likely to receive keratoplasty, while older and lower-income patients more often underwent enucleation/evisceration.

Surgical repair of extracapsular hip fractures is associated with a higher rate of successful healing compared to intracapsular fractures; however, a small subset of patients may still experience complications or treatment failure. Potential modes of failure include nonunion, peri-implant fracture, malalignment, cortical impingement or perforation and hardware failure with or without lag screw cutout. Factors determining salvage method include physiologic age, functionality, bone quality, and fracture stability. In this review, potential complications of extracapsular hip fracture repair are described with proposed solutions and supporting literature, when available.