Faculty Bibliography

OBJECTIVE:We implemented and evaluated a novel score called the blunt thoracic trauma score (BTTS) for the triage of chest wall injury (CWI) patients to optimize utilization of the intensive care unit (ICU). METHOD/METHODS:or Fisher's exact test for categorical variables. Logistic/negative binomial regression models were used to find predictors for ICU admission and length of stay (LOS). RESULTS:Six hundred thirty-three patients were included; 407 pre-BTTS/226 post-BTTS. Pre-BTTShigher median ISS (p < 0.001), more rib fractures (p < 0.001). Post-BTTS older (p < 0.001), more comorbidities (coronary artery disease [p = 0.028], hyperlipidemia [p = 0.004], pulmonary disease [p = 0.038]). Post-BTTS cohort had lower rates of ICU admission (p = 0.008), shorter ICU-LOS (p < 0.001), and Hospital-LOS (p < 0.001). Post-BTTS cohort was associated with shorter Hospital-LOS after adjusting for other factors (p = 0.004). CONCLUSIONS:Implementation of a novel BTTS for triage of CWI was associated with decreased ICU admission rates and shorter ICU-LOS and Hospital-LOS. The decreased Hospital-LOS persisted even after controlling for other factors.

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.

IMPORTANCE/OBJECTIVE:Despite its frequent use for visualization of ureteral efflux during pelvic/abdominal surgery, there are limited data on indigo carmine pharmacokinetics and duration of blue color in postdose urine. Understanding how long the blue color persists allows the clinician to make accurate assessments of the urinary system during complex surgical procedures. OBJECTIVES/OBJECTIVE:This study observed the plasma and urinary pharmacokinetics of indigo carmine in healthy volunteers and the voided urine color. STUDY DESIGN/METHODS:This study was an open-label, randomized clinical trial in 16 healthy participants who received either a 2.5-mL or a 5.0-mL intravenous injection of indigo carmine. Blood (pre, 2, 5, 7, 10, 15, 20, 30, 40 minutes and 1, 2, 3, 4, 6, 12 hours post) and urine (predose, 0-2, 2-6, 6-12 hours post) were collected. The first postdose stool was collected. RESULTS:Plasma concentration peaked within 5 minutes, and all plasma concentrations were below the limit of quantification by 2 hours postdose. The estimated plasma half-life of indigo carmine was 12 minutes. Voided urine through 2 hours postdose was visibly discolored compared with the matched predose urine. In some cases, urine discoloration persisted through 6 hours (10/16) and 12 hours (1/16). Unchanged indigo carmine eliminated in stool was observed in 4 of 16 participants (25%). CONCLUSIONS:The short half-life and rapid urinary excretion of indigo carmine favor its clinical use for intraoperative cystoscopy and are consistent with the reported median time of 6 minutes postinjection to ureteral efflux in patients undergoing surgical procedures.

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.

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.

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.

BACKGROUND:Communication failures are a leading cause of sentinel events in U.S. healthcare, often due to unclear provider contact identification. The electronic health record (EHR) system offers a solution by enabling the discrete assignment of a first contact provider (FCP), who oversees and coordinates patient care. However, adoption of this practice is inconsistent across many hospital settings. This study describes the impact of continuous learning and improvement cycles to address this challenge. METHODS:Following the Plan-Do-Study-Act (PDSA) lifecycle, we completed five quality improvement cycles. Each PDSA cycle included a technological intervention accompanied by evolving operational expectations for clinical staff. We evaluated improvement after each PDSA by measuring the percent of a hospitalized patient's time with an assigned FCP. RESULTS:FCP coverage significantly improved from a baseline average of 5.1% to 59.0% after PDSA Cycle 1 (p < 0.001), 67.4% after Cycle 2 (p < 0.001), 79.7% after Cycle 3 (p < 0.001), 87.5% after Cycle 4 (p < 0.001), and 99.4% after Cycle 5 (p < 0.001). CONCLUSION/CONCLUSIONS:Having a reliable FCP at any point during a patient's hospital admission is an important safety practice. Continuous learning and improvement cycles, driven by a strong partnership between technology and operations, led to significant and sustained improvements in FCP assignments.

INTRODUCTION/BACKGROUND:Although word-finding difficulties (WFD) are prevalent in multiple sclerosis (MS), they remain poorly understood. This cross-sectional study aimed to identify several important practical and theoretical challenges, including key knowledge gaps related to understanding and measuring aspects of language deficit in MS (i.e., WFD). Further investigations of possible correlates of deficits with other symptoms of MS (i.e., such as depression, fatigue and cognitive impairment) were also carried out as part of this study to find out if WFD is a standalone symptom or is a part of a broader and complex symptom of MS. METHODS:In this cohort study, all data from 586 consecutive Persons with MS (PwMS) (137 males and 449 females), with a mean age of 47.1 (SD±10.34) and a median EDSS score of 2.0, were included. A standardized naming task was used as part of a computerized cognitive assessment battery (CAB, NeuroTrax™) with computer-based administration and off-site scoring that has been validated for use in PwMS to determine the associations between cognitive impairment (CI), fatigue, and depression in WFD. RESULTS:A significant correlation (r = 0.327) was noted in this study between cognitive impairment and WFD (p < 0.001). PwMS with CI had a higher rate of WFD (i.e., 43.2%) as compared to individuals with WFD despite not having CI (i.e., 13.9%). Disability (EDSS), disease duration, depression and fatigue, were not correlated with WFD. CONCLUSION/CONCLUSIONS:WFD are most likely part of a larger underlying problem (i.e., CI), but there is a small group of persons with MS and WFD who have isolated WFD. Findings of this study have implications for activities of daily living (ADLs) and therapy for rehabilitation professionals working with PwMS.