Citations

Background/Objectives: Radiofrequency (RF) wire energy can be used for tissue ablation across many conditions. Adjusting RF generator parameters allows RF energy to puncture tissue with minimal adjacent damage. When RF energy is applied to tissue, however, microbubbles are produced, obstructing intravascular ultrasound (IVUS). Mitigation of RF-generated microbubbles has been studied for ablation but not for puncture. Methods: This paper describes an in vitro bench study using ex vivo bovine live tissue. A model was created with bovine liver tissue and an IVUS catheter submerged in a saline bath. Tissue was punctured with an RF guidewire to recreate microbubbles. Following the puncture, various methods were applied: altering the mechanical index of the IVUS, applying a VF10-5 Linear probe (Siemens), and applying a L12-3 Linear probe (Philips). Regions of interest (ROIs) were selected to track pixel brightness as a proxy for microbubbles. Results: The control increased ROI brightness by 1.5%. Altering the mechanical index of IVUS reduced ROI brightness by 1.2%. VF10-5 probe application increased ROI brightness by 1.2%. L12-3 probe application reduced ROI brightness by 33.0% (p = 0.046, n = 3, one-sample t-test). Brightness reduction was most pronounced at the site of initial RF wire puncture, where microbubbles accumulated. Tip visualization improved, allowing for more precise wire trajectory adjustments. Conclusions: External US with an L12-3 probe was able to dissipate microbubbles effectively to improve IVUS guidance following RF wire puncture in an in vitro exploratory bench model.

Background/Objectives: Non-typhoidal Salmonella (NTS) species are well-recognized causes of invasive infection in patients with sickle cell disease (SCD), with a particular predilection for the musculoskeletal system. Although Salmonella osteomyelitis is well described in this population, septic arthritis is uncommon, especially involving the shoulder joint. We describe a case of NTS bacteremia complicated by native shoulder septic arthritis in a patient with SCD and review its clinical implications. Methods: We report the clinical course, diagnostic evaluation, microbiologic findings, imaging studies, and management of a 22-year-old man with homozygous SCD who presented with a vaso-occlusive pain crisis and subsequently developed severe sepsis with persistent Salmonella enterica bacteremia following ingestion of undercooked poultry. Persistent bacteremia prompted further evaluation for metastatic infection using advanced imaging and diagnostic arthrocentesis. Results: Whole-body imaging identified septic arthritis of the native right shoulder, which was confirmed by synovial fluid cultures growing Salmonella species. The patient underwent arthroscopic irrigation and debridement for source control. Antimicrobial therapy was narrowed to intravenous ceftriaxone based on susceptibility data and continued for six weeks. The patient demonstrated clinical improvement with resolution of bacteremia and was discharged to rehabilitation to complete therapy. Conclusions: This case highlights the importance of a careful exposure history, including foodborne sources, in patients with SCD presenting with invasive Salmonella infection. Persistent bacteremia should prompt early investigation for metastatic foci, and timely surgical source control combined with targeted antimicrobial therapy is essential for optimal outcomes in this population.

ABSTRACT Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by antibody‐mediated platelet destruction, often driven by long‐lived plasma cells (LLPCs) resistant to conventional therapies. While most patients respond to corticosteroids and intravenous immunoglobulin (IVIG), a subset develops life‐threatening refractory disease. In this case series, we describe three patients aged 39, 85, and 58 with life‐threatening, multi‐agent refractory ITP and platelet nadirs < 2 × 10 9 /L who failed corticosteroids, IVIG, and thrombopoietin receptor agonists (TPO‐RAs). Following salvage therapy with daratumumab, a monoclonal antibody targeting CD38, all three patients achieved rapid hematologic recovery, with platelet count normalization within 1 week. This accelerated response allowed for urgent clinical stabilization, including safe anticoagulation and surgical intervention. The efficacy of daratumumab likely stems from a dual mechanism: the depletion of CD38+ LLPCs and the immediate modulation of Fc‐receptor‐mediated platelet clearance. These observations suggest that CD38‐targeted therapy can bypass traditional treatment resistance to achieve near‐immediate remission in high‐complexity, high‐risk clinical settings. While these results are compelling, prospective clinical trials are warranted to define the long‐term safety, durability, and optimal dosing of anti‐CD38 therapies in refractory ITP populations.

ABSTRACT Background Academic departments in medicine face increasing pressure to balance clinical productivity with their broader academic missions, including education, scholarship, mentorship, and service. While clinical work is routinely quantified through relative value units (RVUs), non‐clinical academic contributions are inconsistently measured and often undervalued. Academic Value Unit (AVU) systems have emerged as frameworks to quantify these activities, but adoption remains limited due to inconsistent funding models, lack of standardized frameworks, and minimal evidence demonstrating outcomes such as faculty satisfaction, retention, or return on investment (ROI). Methods This concept paper synthesizes current AVU implementation strategies in emergency medicine and proposes an evidence‐informed six‐step framework for AVU design, funding, and sustainability. The framework was informed by a literature review, analysis of institutional dashboards, and multi‐institutional input from the Society for Academic Emergency Medicine (SAEM) community, including feedback from a national didactic session at the 2025 SAEM Annual Meeting. Results The proposed framework outlines practical steps for AVU implementation: defining mission‐aligned domains, identifying measurable academic activities, establishing transparent weighting systems, integrating real‐time tracking dashboards, developing sustainable blended funding models, and engaging leadership and faculty through iterative review. The model incorporates customizable templates, adaptable activity menus, and suggested ROI metrics that departments can tailor to local institutional priorities and resources. Conclusions AVU systems offer a structured approach to recognizing and incentivizing non‐clinical academic contributions in emergency medicine. A transparent, mission‐aligned framework supported by sustainable funding and measurable ROI metrics may enhance faculty engagement, equity, and long‐term departmental sustainability. Future work should focus on establishing validated benchmarks for AVU weighting, integrating AVUs with faculty development and wellness initiatives, and evaluating longitudinal outcomes such as retention, satisfaction, and equity.

A bstract Alzheimer’s disease (AD) presents with substantial clinical and anatomical heterogeneity, including both typical amnestic and atypical variants such as posterior cortical atrophy and logopenic primary progressive aphasia. Although neurofibrillary tangle (NFT) burden is a defining pathological feature of AD, its regional distribution varies across clinical phenotypes, suggesting that selective neuronal vulnerability may shape disease presentation. However, the cellular and molecular determinants underlying this vulnerability remain incompletely understood. Here, we profiled single-nucleus transcriptomes across multiple brain regions, including hippocampal (CA1) and neocortical (superior temporal gyrus and occipital cortex) regions, from individuals with typical and atypical AD and healthy controls. Integrative analysis identified major cell classes and resolved diverse excitatory and inhibitory neuronal subpopulations that were reproducibly observed across regions and individuals. Using quasi-binomial regression models to assess compositional changes, we quantified subtype-specific vulnerability associated with AD pathology. We identified a distinct excitatory neuronal subpopulation characterized by NRGN and BEX1 expression, which showed reproducible depletion across multiple regions, with the strongest evidence in amnestic AD and in neocortical regions in lvPPA. This vulnerable population showed concordance with previously reported AD-associated excitatory neuron signatures, supporting a conserved transcriptional program of susceptibility. Genes enriched in this population were associated with chemical synaptic transmission and regulation of synaptic plasticity and formed interconnected networks in protein-protein interaction analyses. These findings suggest that intrinsic properties related to synaptic function may predispose specific neuronal populations to degeneration in AD. Together, our results define a conserved, transcriptionally distinct excitatory neuron subpopulation that is selectively vulnerable across AD phenotypes and brain regions. This work provides a framework for linking regional pathology to cell-type-specific susceptibility and highlights synaptic regulatory pathways as potential contributors to neuronal degeneration in Alzheimer’s disease.

ABSTRACT BACKGROUND Increasing evidence suggests that accurate prediction of Alzheimer’s disease (AD) symptom onset requires more than amyloid- and tau-centric biomarkers such as cerebrospinal fluid (CSF) Aβ42/40, total tau and p-tau181 and plasma p-tau217. Autosomal dominant AD (ADAD), caused by pathogenic PSEN1, PSEN2 and APP mutations with predictable age at symptom onset, presents a unique opportunity to characterize the chronological changes in proteins beyond amyloid and tau and clarify them as early biomarkers of disease onset or as biomarkers related to disease staging and progression monitoring. METHODS We measured 972 CSF samples corresponding to 484 participants of the Dominantly Inherited Alzheimer Disease Network (DIAN) using the NULISASeq 120 CNS Disease Panel. We first benchmarked the technology against gold-standard measurements followed by the identification of proteins that were differentially abundant in relation to mutation status and symptomatology. Next, we determined the chronological emergence of protein changes in relation to the estimated years to onset (EYO). Finally, we assessed whether specific protein measures improved the prediction of EYO in the ADAD. FINDINGS NULISA measurements were comparable to those previously published. We demonstrated that known early alterations in CSF amyloid and tau were followed by inflammatory and neurodegenerative responses suggesting that clinical manifestation of AD happens before the inflammatory processes is fully developed. Finally, we found a multi-protein composite approach for predicting EYO that outperformed single biomarker values. INTERPRETATION Our results suggest that the main CSF proteomic landscape changes in ADAD are due to the presence of a pathogenic mutation and occur prior to symptom onset. Improved performance of multi-protein composite to predict EYO compared to single biomarker values highlights the added value of multiplex proteomic signatures for biomarker panel development. FUNDING National Institute on Aging, Alzheimer’s Association, German Center for Neurodegenerative Diseases, Raul Carrea Institute for Neurological Research, Japan Agency for Medical Research and Development, Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea, Spanish Institute of Health Carlos III.

Abstract Background DDX3X- syndrome is a rare neurodevelopmental disorder characterized by varying degrees of intellectual disability, predominantly affecting females. We present an institutional cohort supplemented by a systematic literature review, expanding the cardiovascular phenotype of DDX3X- syndrome. Methods We conducted a retrospective chart review of patients diagnosed with DDX3X -syndrome at Mayo Clinic. Additionally, we performed a systematic literature review to identify studies reporting cardiovascular abnormalities in patients with DDX3X -syndrome. Results A total of 200 patients with DDX3X -syndrome were analyzed, comprising 14 patients from our institutional cohort and 186 patients identified through a systematic review of 9 published studies. Our institutional cohort included 14 patients (12 females and 2 males) from 13 unrelated families diagnosed with DDX3X -syndrome, at a median age of 4.5 years (IQR 1.2–9.5). Echocardiogram was performed on nine patients, and cardiovascular abnormalities were found in 7 out of 9 patients who underwent echocardiography (78%), two of whom had major congenital heart defect (CHD) requiring surgical intervention. At the time of assessment, 13 individuals were still alive, while one had died at age six due to extracardiac complications. The systematic review included 9 studies involving 186 patients, of whom 32 (17.4%, 25 females and 7 males) had reported cardiovascular abnormalities, ranging from simple CHDs to more complex defects. Conclusion DDX3X -syndrome carries a significant cardiovascular burden, which is possibly higher than previously reported, including complex congenital heart disease requiring surgical repair. A thorough cardiovascular assessment, including an electrocardiogram and echocardiogram, should be universally recommended for all patients at the time of diagnosis.