Faculty Bibliography

INTRODUCTION/BACKGROUND:The oral microbiome may influence brain health and contribute to cognitive decline. However, little evidence exists on the potential modifying role of the oral microbiome in the relationship between tooth loss and cognitive performance. This study aimed to investigate the interaction effects between tooth loss and oral dysbiotic status on cognitive performance. METHODS:Data were from the 2011-2012 National Health and Nutrition Examination Survey. The sample included 677 adults aged 60 to 69 y. Cognitive performance was assessed by the Consortium to Establish a Registry for Alzheimer's Disease, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test. Significant tooth loss was defined as a loss of ≥10 permanent teeth out of 28. A high dysbiotic index was defined as being in the upper tertile of the ratio of periodontal disease-associated bacteria (Treponema, Porphyromonas, and Tannerella) to healthy bacteria (Rothia and Corynebacterium). RESULTS:A multivariable linear regression model showed a significant interaction effect between tooth loss and dysbiotic index on the AFT (b = -1.87, P = 0.03), indicating that participants with a higher dysbiosis index and fewer missing teeth scored lower on the AFT. CONCLUSIONS:The effect of tooth loss on verbal fluency depends on oral bacterial imbalances: if there is significant tooth loss, bacterial imbalances may not be important. However, when fewer teeth are lost, high bacterial imbalances may account for lower verbal fluency. These findings suggest that maintaining periodontal health aimed at decreasing oral dysbiosis should be promoted among older adults in the community.Knowledge Transfer Statement:Our findings highlight the importance of preserving the health of the teeth and not just retaining the teeth. Oral health awareness and good oral hygiene practice should be further promoted among older adults in the community.

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.

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.

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.

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 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.

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.