Citations

Daptomycin-resistant Enterococcus faecium (DRE) poses an increasing therapeutic challenge, particularly in immunocompromised patients and solid organ transplant recipients. Surveillance data from the Centers for Disease Control and Prevention indicate that approximately 6.5% of E. faecium isolates are daptomycin-resistant, underscoring the need for heightened clinical vigilance, particularly for prompt identification and treatment. In this case series, three patients with advanced liver disease, including two status post orthotopic liver transplantation, are described who developed DRE during treatment for bloodstream infection. These cases illustrate the dynamic nature of antimicrobial susceptibility under daptomycin exposure and highlight the contributions of persistent source control issues, intravascular infection, and altered host factors to treatment failure. All patients were successfully managed by escalating to combination therapy with high-dose daptomycin and ceftaroline, alongside appropriate source control. This series emphasizes the importance of periodic susceptibility reassessment during daptomycin therapy and cautions clinicians against assuming sustained susceptibility in patients with prolonged bacteremia or complex infections. Early recognition of evolving resistance and timely therapeutic adjustment may improve outcomes in this high-risk population.

Introduction: Congenital preauricular lesions, including skin tags, accessory tragi, and pits, have long been associated with renal anomalies due to their shared embryologic origin. Despite the common practice of recommending routine renal ultrasound screening for these patients, the necessity of this protocol has not been conclusively validated. Methods: A retrospective review was conducted at a single institution from 1996 to 2025. A total of 109 patients presenting with congenital preauricular lesions were identified. Data extracted included demographics, comorbidities, syndromic status, hearing assessments, external ear abnormalities, and renal imaging findings. Statistical analyses (chi-square, Fisher's exact test, and one-sample proportion z-tests) were employed to evaluate the prevalence of renal anomalies compared to the general population and explore associations with other clinical factors. Results: Of the 109 patients with congenital preauricular lesions, 69 underwent renal imaging, and 34.8% (24/69) were found to have abnormal findings, significantly higher ( P = .0011) than the estimated 1.5% prevalence among the general US population. Hydronephrosis was the most frequent abnormality, while no significant differences emerged across syndromic versus nonsyndromic patients, external ear anomalies, or documented hearing loss. Conclusion: These findings indicate a higher-than-expected rate of renal pathology in patients with congenital preauricular lesions and support a low threshold for imaging regardless of syndromic status or other risk factors. Prospective research is needed to further refine screening recommendations.

Abstract Background Despite the high precision of deep learning models on internal tests on CT, their effectiveness often drops on external validation due to artifacts caused by patient motion and implants like metal or silicone that were not accounted for in the carefully curated training data. Potential wide categories of “unknown” anomalies within a CT exam makes training a supervised model for out‐of‐distribution (OOD) identification impractical, especially when considering unseen external data. Purpose To develop an artificial intelligence (AI) model to detect and identify anomalies/OOD data in abdominal–pelvis CT exams for the purpose of improving the performance of downstream applications. Methods Our proposed 2D and 3D generative architecture receives the third lumbar vertebra (L3) slice (slice‐level model) or all the slices from the series (series‐level model), generates a reconstruction and the secondary part of our architecture—anomaly score computation block, computes the anomalies pixels/voxels (slice‐level/series‐level) to identify anomalous L3‐slices/volumes (slice‐level/series‐level). We trained on data from over 2850 abdominal–pelvis CT volumes from adults over age 50 years collected throughout multiple Mayo Clinic campuses (60% female; mean age: 66.9, 92.4% non‐Hispanic White) and tested on a prospective test set of 544 CTs from July 2024 (47.3% female; mean age: 70.9, 94% non‐Hispanic White) as well as an external test set. Results We found that while traditional methods show moderate success, our generative models—Vector Quantized Variational Autoencoder (VQVAE) and Vision Transformer‐Masked Autoencoder (VIT‐MAE)—deliver excellent results with negligible false positives (FPs) and are also superior in identifying varied types of OOD samples. Prospective analysis showed the model was able to handle the under‐documentation of anomaly in radiology reports with 86.11% true positive (TP) rate. We also performed external validation using the publicly available AbdominalCT‐1k dataset, which contains 1062 CT scans compiled from several existing benchmark datasets. The model achieved a 75.26% TP rate, while the 24.7% FP rate was primarily triggered by anomalies located outside the body. Conclusions The proposed method can be leveraged to detect both intra‐ and interclass OOD data from abdominal CT images and can assess the quality of CT datasets to provide actionable insights. This workflow is particularly valuable for nonshareable healthcare collaborations, where it can be deployed as a service within local firewalls for automated dataset curation without prior knowledge about the OOD types. The implementation of the algorithm is available in the GitHub: https://github.com/gokul‐ramasamy/implant_detection.git .

Background and Objectives: Despite wide agreement on the importance of building research capacity to the specialty of family medicine, no standard exists for defining or measuring that growth. Previous work to address this gap yielded the Productivity and Capacity Evaluation in Research (PACER) Tool, a list of quantitative research metrics grouped into seven categories. We surveyed family medicine department chairs to understand which categories of PACER metrics they considered most valuable in evaluating their department’s research capacity. We also aimed to compare reported research capacity in 2024 with answers given by family medicine department chairs in 2021. Methods: A cross-sectional survey administered through the Council of Academic Family Medicine Educational Research Alliance (CERA) was used to gather information from family medicine department chairs in the United States and Canada. One question asked chairs to evaluate their department’s research capacity, and nine questions assessed the relative importance of the seven PACER Tool categories. Results: A total of 218 surveys were delivered, with 111 (50.9%) completed. Survey results demonstrated that program chairs determined funding to be the most impactful category. We found no clear trend in the second most important or least important categories. Results also showed no statistically significant change in reported research capacity between 2021 and 2024. Conclusions: Funding emerged as the category of research metrics viewed as most important by the greatest number of family medicine department chairs. Although other categories of metrics also were viewed as important, this survey demonstrated no clear pattern of their relative importance in this population.

CEUS is a safe and cost-effective means for characterization of indeterminate renal masses, with performance equal to or better than that of contrast-enhanced CT or MRI for stratification and surveillance of cystic renal masses and discrimination of benign avascular cysts from solid renal masses.

Background: Postoperative emergency department (ED) utilization significantly reduces patient satisfaction and increases health care spending. Purpose: To identify the incidence, risk factors, and reasons for ED visits within 90 days of Achilles tendon repair (ATR). Study Design: Case-control study; Level of evidence, 3 Methods: This study utilized the PearlDiver database to identify all instances of primary ATR. Patient age, sex, Elixhauser comorbidity index (ECI), region, and insurance coverage were extracted. The incidence, timing, and primary diagnoses for those with an ED visit 90 days post-ATR were extracted. Also, the 90-day total cost was determined and compared for those with and without a postoperative ED visit. Welch t test and Pearson chi-square test were used to determine significant differences between groups. Multivariable logistic regressions were used to determine risk factors associated with ED utilization after ATR. Results: Of the 82,604 patients with an ATR identified in the database, 6939 (8.4%) had ≥1 ED visit. Of ED visits, 1506 (21.7%) occurred in the first week after ATR and 3587 (51.7%) occurred in the first 4 weeks after ATR. The mean 90-day cost for those with an ED visit was significantly greater than those without an ED visit ($7330 ± $13,383 vs $3515 ± $5787; P < .001). Independent risk factors associated with ED utilization within 90 days were younger age (odds ratio [OR], 1.02; P < .001), female sex (OR, 1.26; P < .001), higher ECI (OR, 1.17; P < .001), a history of tobacco use (OR, 1.57; P < .001), and having Medicaid insurance (OR, 1.73; P < .001). Most ED visits within the first 2 weeks after ATR were for surgical-site pain (53.6%), with 62.4% of diagnoses being directly related to the surgical site. After 2 weeks following ATR, pain persisted as the most common reason for ED utilization (20.9%). Conclusion: More than 8% of patients had ≥1 ED visit within 90 days of ATR, with over half occurring in the first 4 weeks. This markedly increased health care spending. Addressing regional disparities, improving Medicaid acceptance policies, and enhancing perioperative care plans, such as multimodal pain management and addressing the psychological aspects of pain, may reduce the incidence and economic burden of postoperative ED visits.

Abstract Background: Despite the success treating hematologic malignancies, chimeric antigen receptor T-cell (CAR T) therapies face challenges in breast cancer and other solid tumors due to lack of targets that distinguish tumor from normal cells. Epithelial growth factor receptor (EGFR) plays a critical role in oncogenesis across several cancers and is often upregulated [1]. While monoclonal antibodies targeting EGFR have demonstrated efficacy, these approaches are often limited by on-target, off-tumor toxicities, such as skin and gastrointestinal toxicity, which constrains dose escalation and efficacy [2]. A2B395 is an allogeneic, logic-gated, EGFR-targeted, TmodTM CAR T therapy designed to address these limitations and provide a convenient and consistent off-the-shelf option. This therapy incorporates 2 CARs: an activator targeting EGFR and a blocker targeting human leukocyte antigen (HLA)-A*02. The activator recognizes EGFR on both tumor and normal cells, whereas the blocker inhibits CAR T activity against normal cells (with preserved HLA expression) while allowing activation against tumor cells (with HLA-A*02 loss of heterozygosity [LOH]). This approach is designed to avoid on-target, off-tumor toxicity, a significant limitation to CAR T treatment of solid tumors [3]. To address potential graft-vs-host response, a short-hairpin RNA expression module targeting beta-2 microglobulin is included in the Tmod construct, which significantly reduces major histocompatibility complex class I levels and subsequent host immune response [4]. Importantly, the Tmod system is modular and adaptable to multiple targets. Initial data on autologous Tmod CAR T therapy suggest reduced off-tumor toxicity and encouraging clinical efficacy [5]. A2B395 represents a novel approach for targeting EGFR-expressing solid tumors with HLA-A*02 loss of heterozygosity. Methods: DENALI-1 is a phase 1/2, open-label, nonrandomized study evaluating the safety and efficacy of A2B395 in adults. Patients are enrolled through BASECAMP-1 (NCT04981119), a master prescreening study that identifies patients with HLA loss of heterozygosity at any time in the course of their disease via next-generation sequencing. Key inclusion criteria include histologically confirmed recurrent, unresectable, locally advanced, or metastatic cancers associated with EGFR expression, including triple-negative breast, colorectal, non-small cell lung, squamous cell head and neck, and renal cell cancers. Patients must have received ≥1 line of prior therapy, such as a checkpoint inhibitor, molecular targeted therapy, or chemotherapy. The primary objective of the phase 1 portion is to evaluate safety, tolerability, and the recommended phase 2 dose (RP2D) using a Bayesian optimal interval design for dose escalation. The dose-expansion phase will confirm the RP2D and collect and analyze biomarker data. The Phase 2 portion will assess overall response rate per RECIST v1.1. As of 03 July 2025, the first patient dosed with A2B395, who has breast cancer, completed the 28-day safety review period. Dose-escalation is ongoing. Citation Format: J. M. Specht, S. R. Punekar, M. Ulrickson, D. J. Wong, J. R. Hecht, M. Maus, P. M. Grierson, J. B. Sunwoo, J. R. Molina, D. G. Maloney, K. Spencer, H. E. Fuentes Bayne, M. Davila, S. P. Patel, B. Creelan, D. B. Zhen, J. Niu, D. C. Prasad, R. L. Marar, N. A. Bagegni, G. Palluconi, J. Lee, A. Mardiros, W. Bretzlaff, W. J. Langeberg, J. S. Welch, E. Ng, W. Y. Go, K. Kirtane, R. A. Shatsky. Denali-1: a seamless phase 1/2 study of A2B395, a logic-gated, allogeneic, Tmod chimeric antigen receptor T-cell (CAR T) therapy, in patients with triple-negative breast cancer and other EGFR-expressing solid tumors with HLA-A*02 loss of heterozygosity (LOH) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-08-03.