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.

Current CardioMEMS HF System (Abbott) instructions for use recommend against implantation in obese patients (body mass index >35 kg/m²) whose chest circumference exceeds 165 cm, as placement can be technically challenging and remote interrogation can be unreliable. We present a case of successful CardioMEMS implantation in a patient with significant morbid obesity, exceeding previously reported body size limits, with a body mass index of 77.1 kg/m² and chest circumference of 178 cm. Outpatient device interrogation following implantation has been reliable in optimizing diuretic management and preventing readmissions in this patient.

INTRODUCTION/BACKGROUND:Hemispherotomy is an effective treatment for children with drug-resistant epilepsy (DRE). While hemispherotomy techniques and indications have evolved, access remains predominantly constrained to high-resource settings. METHODS:We performed a retrospective analysis of children who underwent hemispherotomy from 2011 to 2023 by a hybrid team, including local Panamanian and US neurologists, neurosurgeons, and EEG technicians and analyzed surgical, epilepsy, and quality of life (QoL) parameters. Follow-up data were collected according to the International Consortium for Health Outcomes Measurement (ICHOM) guidelines for children with epilepsy. RESULTS:Twenty-three children underwent hemispherotomy. The median age at surgery was 10 years (range 2-20). The median follow-up time was 6 years (range 1-13). The etiology of DRE included malformations of cortical development in 14 children (60.8%), including 8 (34.8%) with schizencephaly, and secondary causes in 9 children (39.1%). Seizure frequency improved for all 23 children (100%): Engel I was achieved in 15 children (65.2%), Engel II (26.1%) in six children, and Engel III (8.7%) in two children. Patients with seizure freedom had significantly fewer preoperative seizures per day than patients with seizure recurrence. Complications occurred in six children (26.1%): 2 wound infections, 2 meningitis, 1 femoral vein thrombosis, and 1 wound hematoma with return to OR. There were no perioperative mortality and no postoperative hydrocephalus or CSF diversion. QoL-related outcomes were available for 16 children: 16/16 (100%) reported that the surgery was a worthwhile and repeatable choice, 14 (87.5%) reported improved cognitive function, the median QOLCE-16 score was 62.5 ± 21. CONCLUSION/CONCLUSIONS:Hemispherotomy for DRE in selected children is a safe and effective surgery in a public children's hospital in a low-resource setting. At last follow-up, the majority of children were seizure-free, and all children had decreased seizure frequency. Families reported improved cognitive function, improved QoL and high satisfaction with their decision to pursue this surgery.

PURPOSE/UNASSIGNED:Understanding medical students' readiness to perform basic entrustable professional activities (EPAs) informs tailored support during transition to residency. METHODS/UNASSIGNED:Night-onCall (NOC) was developed to assess medical student readiness to perform core EPAs on day one of internship. NOC is a complex, integrated simulation centered around three clinical cases. Assessments include standardized patient (SP), nurse (SN), physician attending (SA), and resident (SR) perspectives using clinical competency rating instruments mapped to EPAs and scored as Well Done (WD), Partly Done (PD) or Not Done (ND). Faculty rate clinical reasoning using a rubric evaluating written post-encounter notes as poor, beginning, competent, or strong. The ability to recognize lapses in patient safety is assessed based on written case responses. Medical librarians evaluate students' ability to formulate a clinical question and search for evidence. RESULTS/UNASSIGNED:Data was collected from 'near-graduates' from seven USA medical schools from 2020 to 2023 (n = 1116). Overall, SPs rated 75.0% of overall communication skills and only 56% of patient education items as WD. SNs rated interprofessional communication 57.0% WD, and SRs rated intraprofessional communication 61.0% WD. History gathering and physical exam skills varied by case. Faculty rated clinical reasoning as beginning (45%) or competent (44%) and librarians rated 16% of literature searches as WD. CONCLUSION/UNASSIGNED:Most near-graduates demonstrated competent basic patient communication skills but performed less well on patient education, communication with other team members, clinical reasoning, and accessing the evidence base to answer clinical questions. These overall trends, consistent across schools and year, provide benchmarks for clinical training.

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.

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.

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.

The 2025 World Allergy Organization (WAO) Guidelines for the Classification, Diagnosis, and Treatment of Hereditary Angioedema (HAE) with Consideration of Worldwide Disparities provide a comprehensive, evidence-informed, and globally applicable framework for the care of this rare and potentially life-threatening disorder. HAE is a genetic disease characterized by recurrent episodes of subcutaneous and submucosal swelling, most commonly mediated by bradykinin, and is associated with substantial morbidity, impaired quality of life, and a lifelong risk of fatal laryngeal edema. The Guidelines were developed by an international panel of 40 experts from 22 countries, with representation from all world regions, reflecting the commitment of WAO to geographic diversity, inclusiveness, and global relevance. The development process for these guidelines followed a structured and transparent methodology that integrated systematic literature review, appraisal of real-world evidence, and application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework adapted for rare diseases, complemented by a formal Delphi consensus process. This approach was specifically designed to address the limitations of conventional evidence hierarchies in rare disorders, while ensuring clinical applicability across heterogeneous healthcare systems and resource settings. A central element of the guidelines is an updated classification of HAE based on underlying pathophysiology and disease endotypes. The traditional distinction between HAE types 1 and 2 is unified under the term HAE with C1 inhibitor deficiency (HAE-C1-INH), reflecting shared biological mechanisms and management principles. The guidelines also recognize an expanding spectrum of HAE with normal C1 inhibitor (HAE-nC1-INH), including forms associated with pathogenic variants in F12, PLG, ANGPT1, KNG1, MYOF, HS3ST6, CPN1, and DAB2IP, as well as cases with currently unidentified genetic causes. The diagnostic strategy emphasizes early clinical recognition based on characteristic features, including recurrent angioedema without urticaria, abdominal or laryngeal involvement, early symptom onset, and family history. A simplified diagnostic algorithm is proposed, prioritizing the C1 inhibitor functional assay as the preferred initial test when performed in a reliable specialized laboratory. Alternative diagnostic pathways are outlined for settings with limited access to specialized testing, including pragmatic combinations of biochemical assays and selective use of genetic testing, particularly relevant for HAE-nC1-INH and family screening. Management recommendations address on-demand treatment of acute attacks, short-term prophylaxis, and individualized long-term prophylaxis. Universal access to on-demand therapy is emphasized for all patients with confirmed HAE, including those who are asymptomatic, given the unpredictable nature of attacks and lifelong risk. Long-term prophylaxis is addressed within a treat-to-target framework aimed at achieving complete disease control and sustained improvement in health-related quality of life, with regular reassessment and shared decision-making. Empowering patients and caregivers through structured education, access to appropriate medications, and integration with specialized referral centers is associated with earlier treatment, reduced healthcare utilization, and improved equity of care and reduced avoidable morbidity and mortality worldwide. The 2025 WAO Guidelines for Hereditary Angioedema establish an evidence-informed, patient-centered, and forward-looking framework for the classification, diagnosis, and management of HAE. By integrating advances in pathophysiology, diagnostics, and therapeutics with global expert consensus and real-world considerations, the guidelines aim to support consistent, equitable, and high-quality care for patients with HAE across regions and healthcare systems.

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.

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.