Faculty Bibliography

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.

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.

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.

PURPOSE OF REVIEW/OBJECTIVE:Aeroallergens are well established triggers of allergic rhinitis and asthma, yet their contribution to allergic skin diseases such as atopic dermatitis (AD) and chronic urticaria (CU) remains incompletely understood. This article reviews the molecular basis of aeroallergen-driven skin disease in AD and CU as well as management strategies. RECENT FINDINGS/RESULTS:Aeroallergen triggered skin disease involves epithelial barrier disruption, innate immune activation, and neuroimmune amplification. Allergen disruption of the epithelial barrier through PAR-2 and TLR-mediated signaling, induces alarmins that sustain an IL-31-driven itch-scratch cycle. Biologics targeting these pathways reshape these cytokine networks, while checkpoint inhibitors show promise for durable remission. In CU, house dust mite sensitization correlates with basophil hyperreactivity and greater disease severity. Aeroallergen triggered inflammation involves overlapping barrier dysfunction, innate immune activation, and neuroimmune pathways that extend beyond traditional IgE-mediated allergic responses. Future research should prioritize endotype-based patient stratification and quantify the impact of aeroallergen exposure on chronic skin disease trajectory.

Sepsis is a systemic inflammatory disorder marked by dysregulated inflammation and coagulopathy. Annexin A2 (A2), a profibrinolytic protein, assembles plasminogen and tissue plasminogen activator on cell surfaces, thereby maintaining vascular patency. However, its role in human sepsis has remained poorly defined. We investigated whether A2 undergoes qualitative or quantitative modification during human sepsis with associated end-organ dysfunction. Peripheral blood mononuclear cells and plasma were collected from 65 patients with sepsis and 27 healthy controls. A2 expression and integrity were evaluated with cell surface plasmin generation using immunoblot and fluorometric assays. Both A2 integrity and plasmin generation were significantly reduced in patients with sepsis and with septic shock. A2 underwent sepsis-related membrane-associated proteolysis mediated by a serine protease. A2 reduction correlated with interleukin-18 levels and was significantly associated with renal, pulmonary, cardiovascular, and neurologic dysfunction. A2 proteolysis may represent a novel biomarker and therapeutic target for sepsis-related microvasculopathy.

IMPORTANCE/UNASSIGNED:Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. OBJECTIVE/UNASSIGNED:To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. EXPOSURES/UNASSIGNED:Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy-related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. RESULTS/UNASSIGNED:Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate (P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). CONCLUSIONS AND RELEVANCE/UNASSIGNED:These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01915615.