Faculty Bibliography

CONTEXT/BACKGROUND:Traumatic musculoskeletal injuries may result in chronic pain and mobility limitations, decreasing quality of life, and increasing predisposition to comorbid disorders. Osteopathic manipulative treatment (OMT) utilizes palpatory assessment and application of manual forces as an adjunct intervention for musculoskeletal disease. Multiple studies have demonstrated OMT's potential benefits for a range of disease states, but data on osteopathic OMT are limited. OBJECTIVES/OBJECTIVE:The objective of our study was to understand the potential benefits of a novel OMT for trauma outpatient program for the care of injured patients suffering chronic pain and mobility limitations. METHODS:In 2021, the New York University (NYU) Langone Hospital - Long Island Level 1 Trauma Center established a novel outpatient OMT for Trauma Program (OTP). We performed a retrospective analysis of OTP patients seen from January 1, 2021 to December 31, 2022 with the chief complaint of refractory chronic (persistent ≥3 months since inciting injury) postinjury pain and mobility limitations (inclusion criterion). We excluded patients missing follow-up, then extracted and analyzed patient demographic, injury-specific, and OMT data. Data are presented as frequencies (percentages) or medians (interquartile range [IQR]). RESULTS:Forty-three patients (75.4 % of patients treated at the outpatient OTP) reported a mechanism of injury (MOI). Of these, 30 (69.8 %) met the inclusion criteria, and seven met the exclusion criterion, yielding 23 total patients for the analysis (40.3 % of the total OTP population). 73.9 % were female aged 46 (39-59) years old. Patients presented 3.00 (0.58-20) years since etiologic injury. MOIs included 56.5 % motor vehicle collisions (MVC), 21.7 % falls, 8.7 % penetrating, and 13.0 % sports-related or lifting injuries. Patients reported 3 (2-4) treatment modalities tried and 2 (1-3) medications attempted prior to the OTP. After the first OMT session, 95.7 % of patients reported subjective improvement in pain with a decrease in pain score 3 (3-7) out of 10. After OMT, patients also self-reported ease of activities of daily living (ADLs, 82.6 %), improved sleep hygiene (26.1 %), improved anxiety/mood (65.2 %), and decreased use of analgesic medication (13.0 %). Four (17.4 %) reported post-OMT complication of 2-3 days of self-limited, mild musculoskeletal pain. Univariate logistic regression models demonstrate that OMT benefited patients regardless of time since inciting injury. CONCLUSIONS:OMT may benefit refractory chronic traumatic pain and mobility limitations regardless of the time since inciting the injury. This is the first major publication from the OTP and bolsters proof-of-concept for an organized OMT program at a level 1 trauma center. Further study, including comparative analysis with more formalized pain assessments utilizing validated tools as well as standardized OMT session surveys, is warranted.

OBJECTIVE:To develop, implement, and assess the utility of a standardized letter of evaluation (SLOE) for OBGYN residency applicants in the US. DESIGN/METHODS:OBGYN program directors (PDs) were surveyed over 2 consecutive years and asked to estimate the percentage of applicants submitting an SLOE and to indicate its helpfulness compared to traditional letters of recommendation. Sub-group analysis by program type was performed. In 2023, comments for improvement were collected and analyzed for themes using a large language model. SETTING/METHODS:OB/GYN residency programs in the United States. PARTICIPANTS/METHODS:OB/GYN PDs in the United States. RESULTS:The survey was completed by 254 of 293 (86.7%) of PDs in 2022 and 253/293 (86.3%) in 2023. From 2022 to 2023, there was no difference in the estimated percentage of applicants who submitted an SLOE to a program (median 50%-74%), though in 2023, university and combined university-community programs estimated receiving higher percentage of applicants submitting SLOEs compared to community and military programs (p < 0.001). Over the study period, the favorability of the SLOE improved, and feedback indicates a need for continued improvement in the SLOE process, including faculty development, standardization, and more honest assessment of applicants. CONCLUSIONS:An SLOE was submitted by most applicants to OBGYN residency programs. Iterative modification of the SLOE based on PD, applicant, and faculty advisor feedback is needed to assess its utility in the application process.

Prader-Willi syndrome (PWS) is a rare genetic disorder marked by metabolic, endocrine, and behavioral challenges, with hyperphagia as a central feature contributing to significant health risks. Diazoxide choline extended-release (DCCR; VYKAT™ XR) is a once-daily adenosine triphosphate (ATP)-sensitive potassium channel activator recently approved for the treatment of hyperphagia in individuals with genetically confirmed PWS aged 4 years and older. As this novel therapy enters clinical practice, clinicians require practical guidance on appropriate use. This manuscript provides actionable recommendations for patient selection, baseline assessments, and strategies for optimizing comorbid conditions prior to initiation. Structured, weight-based dosing and titration protocols are outlined, along with recommendations for monitoring glycemia and edema and managing common adverse events (AEs), including hyperglycemia, peripheral edema, and rash. Special considerations are discussed for patients with diabetes, cardiopulmonary risk factors, and those on concomitant medications with potential drug-drug interactions. The guidance is informed by data from the phase 3 DESTINY-PWS program, long-term extension studies, and real-world clinical experience. Emphasis is placed on early identification and management of AEs and the importance of a multidisciplinary approach to care. These recommendations aim to support clinicians in safely and effectively incorporating DCCR into the management of PWS, improving outcomes for affected individuals. Ongoing research and real-world evidence will continue to refine best practices and address remaining gaps in knowledge.

OBJECTIVE:Leveraging large language models (LLM), we identified an unregistered subpopulation of individuals with World Trade Center-related exposure and lung cancer who were not previously captured in registries, and assessed how this exposure impacted patients' disease course. METHODS:Associations between exposure type and smoking history, cancer stage, mutation status, disease progression, and survival were statistically analyzed. RESULTS:The highest proportion of never-smokers was observed among residents, compared to first responders and commuters (19% and 24%; p = 0.005). Residents had more than twice the risk of disease progression (HR = 2.14, p = 0.008) and an elevated risk of death (HR = 2.43, p = 0.03). Only EGFR mutations were significantly associated with exposure type (p = 0.01). CONCLUSIONS:This work highlights that LLM can capture a greater population of WTC survivors, including genetics.

Lysosomal phospholipid degradation produces two types of metabolites, either 2-lysophospholipids with saturated fatty acids in sn-1 position or 1-lysophospholipids with unsaturated fatty acids in sn-2 position. They may either be degraded further or re-used for phospholipid synthesis. We found that LPLAT7 (LPGAT1), an acyltransferase of the endoplasmic reticulum, re-acylates specifically lysosome-derived 1-lysophospholipids that carry an unsaturated chain. The enzymatic activity of LPLAT7 was specific for stearoyl-CoA and 1-lyso-2-acyl positional isomers of unsaturated lysophospholipids. In Huh7 cells, Lplat7 knockout prevented the reacylation of 1-lysophospholipids generated by the lysosomal degradation of exogenous ²H-phosphatidylcholine. Inhibition of lysosomal phospholipid degradation reduced the abundance of 1-stearoyl-2-unsaturated PC in Huh7 cells. Lplat7 knockout blunted the loss of unsaturated lysophosphatidylcholine (LPC) in response to lysosomal inhibition, suggesting that LPLAT7 consumes unsaturated LPC formed by lysosomes. In mice, Lplat7 knockout increased the concentration of unsaturated lysophospholipids, reduced the abundance of 1-stearoyl-2-unsaturated species of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, and inhibited the regeneration of cellular membranes. It also triggered the accumulation of triglycerides, confirming earlier reports that unsaturated lysophospholipids induce lipid droplet formation. Thus, by re-acylating unsaturated 1-lysophospholipids, LPLAT7 shifts lipid metabolism from the biogenesis of lipid droplets to the biogenesis of membranes.

Although the largest completely symmetric closed assembly that can be built from a single building block is the 60-subunit icosahedron¹, viruses can form capsid assemblies with hundreds to thousands of identical subunits through quasisymmetry-using the same subunit in symmetrically non-equivalent locations in the assembly^2-5. Quasisymmetric one-component assemblies could have considerable advantages for delivery of biologics because of the large internal volume achieved using only a single building block, but the design of these structures is challenging because of the inherent complexity of designing chemically identical subunits to both adopt different conformations and make different interactions in the distinct symmetrically non-equivalent locations. Here we conjectured that quasisymmetry could arise from spontaneous symmetry breaking in a system of strongly interacting building blocks with programmed curvatures and show that this principle, coupled with a design approach combining a parametric representation of cage architecture with RoseTTAFold diffusion generative modelling, can generate a rich array of quasisymmetric assemblies. Electron microscopy confirmed the structures of designed 3 ≤ T ≤ 36 cages with 180-2,160 subunits and diameters from 68 nm to 220 nm, and designed 1 < T < 3 non-icosahedral clathrin-like assemblies. Cryogenic electron microscopy structure determination showed how the global symmetry breaking associated with the formation of both hexons and pentons in the T = 3 architecture arises from symmetry breaking in the designed subunit interface. Our results indicate how the detailed architecture of complex systems can be controlled by designing overall system properties, and our approach provides a roadmap for designing large quasisymmetric assemblies for biologics delivery and other applications.

CONTEXT:The hallmark condition of Prader-Willi syndrome, a rare, genetic neurobehavioral/metabolic disorder is life-threatening hyperphagia. OBJECTIVE:We assessed the efficacy and safety of recently FDA-approved diazoxide choline extended-release (DCCR) tablets for the treatment of hyperphagia in adults and children four years of age and older with Prader-Willi syndrome. METHODS:We conducted a 16-week, randomized withdrawal study in children and adults with Prader-Willi syndrome and hyperphagia. Participants who previously completed randomized (13-week DCCR or placebo) and open-label (2.5-4.5 years DCCR) studies were randomized one:one to receive once-daily DCCR or placebo. The primary endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total score change from baseline to 16 weeks. Secondary endpoints included Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I); exploratory endpoints included weight and body mass index (BMI) z-score. RESULTS:Seventy-seven participants were randomized (DCCR:38; placebo:39). Statistically significant increases in HQ-CT from baseline to week 16 were observed with placebo versus DCCR (least square [LS] mean [standard error] change 7.6 [1.09] with placebo and 2.6 [1.12] with DCCR; P=0.0022). CGI scores favored DCCR but were not significantly changed. Consistent with the hyperphagia response, the placebo cohort gained more weight and increased their BMI z-score more than the DCCR cohort (LS mean weight difference (95% confidence interval) -1.6 kg (-3.1, -0.1); LS mean z-score difference -0.09 (-0.17, -0.01). Adverse events were similar with both treatments, with no serious adverse events in the DCCR arm. CONCLUSIONS:Continued DCCR treatment was superior to placebo for hyperphagia. DCCR appears to offer meaningful therapeutic benefits for people with Prader-Willi syndrome.

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. An evidence-based methodology is used, with a MEDLINE literature search to identify pertinent clinical studies on the topic and a Manufacturer and User Facility Device Experience (U.S. Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported adverse events of a given technology. Both are supplemented by accessing the "related articles" feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but in many cases, data from randomized controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinion are used. Technical data are gathered from traditional and web-based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the ASGE Governing Board. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through March 2025 for articles related to pancreaticobiliary stricture management. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. They are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment.

OBJECTIVE:Vascular calcification (VC), characterized by abnormal calcium salts buildup in blood vessels, greatly raises the risk of adverse cardiovascular events. However, the mechanisms behind VC are not fully understood. Nogo-B, a member of the reticulon family, has been implicated in various pathological processes including intimal neovascularization, obesity, and metabolic-associated fatty liver disease. Yet, its role in VC has not been explored. APPROACH AND RESULTS/RESULTS:). An ex vivo osteogenic model employing human arteries and an in vitro osteogenic model using human aortic smooth muscle cells (HASMCs) were both created under high phosphate conditions. Nogo-B expression was significantly downregulated in calcified human and mouse aortas, as well as in high phosphate-treated HASMCs. Additionally, SMC-specific knockout of Nogo-B exacerbated VC. Conversely, overexpressing Nogo-B suppressed osteogenic differentiation of HASMCs. Mechanistically, Nogo-B inhibited VC by upregulating the expression of the amino acid transporter SLC7A11. Nogo-B strongly interacts with SLC7A11 and promotes recruitment of the deubiquitinating enzyme OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1), thereby preventing K63-linked ubiquitination of SLC7A11 at K30. Furthermore, Nogo-B-mediated upregulation of SLC7A11 boosted intracellular glutathione (GSH) synthesis, which activated NRF2. NRF2 functions as a transcriptional enhancer of SLC7A11. Ultimately, Nogo-B activated antioxidant defense and alleviated oxidative stress to suppress vascular calcification. CONCLUSION/CONCLUSIONS:This study identifies Nogo-B as a novel regulator of VC. Nogo-B stabilizes the SLC7A11 protein by modulating OTUB1-mediated deubiquitination and enhances the GSH/NRF2 signaling axis, thereby promoting glutathione synthesis, reducing oxidative stress, and inhibiting the osteogenic differentiation of VSMCs and VC progression.