Citations

Abstract Background and Objectives Cryoprecipitated antihemophilic factor (cryoprecipitate), fibrinogen concentrate (FC), and pathogen‐reduced cryoprecipitated fibrinogen complex (PR cryoprecipitate) are sources of fibrinogen replacement, and each has advantages and disadvantages in terms of cost, efficacy, safety, and logistics of administration. This study examines the respective utilization frequencies of these different products at institutions in North America and the factors influencing the decision on which one(s) to adopt. Materials and Methods A survey was distributed via email to contacts for Advancement of Blood and Biotherapies (AABB)‐accredited blood banks/transfusion services. Survey questions covered topics including the availability and usage of FC, cryoprecipitate, and PR cryoprecipitate, as well as the perceived advantages of each product. Results A total of 53 responses were received from surveyed institutions (estimated 25% response rate). Over half (31/53, 58.5%) of respondents exclusively used cryoprecipitate, 30.2% (16/53) used two sources of fibrinogen replacement, and 7.5% (4/53) used all three (cryoprecipitate, FC, and PR cryoprecipitate). More than half of the institutions restricted FC to specific indications, primarily for cost containment. The most commonly cited advantages of FC over cryoprecipitate were storage convenience and rapid reconstitution. Conclusion Surveyed institutions in the United States and Canada primarily use cryoprecipitate for fibrinogen replacement, with variable usage of FC and limited usage of PR cryoprecipitate. The perception of FC being more expensive than cryoprecipitate predominated. Further studies comparing available fibrinogen replacement options would be valuable, particularly with consideration of product acquisition cost, wastage, impacts on utilization of other blood products, and patient outcomes.

Background: Infection following extensor mechanism reconstruction (EMR) with Marlex mesh (C.R. Bard) is devastating and limb-threatening. The purpose of this study was to evaluate whether vancomycin-loaded mesh reduces staphylococcal infection in a murine EMR model. Methods: Mouse-sized, 8-layer mesh constructs were fabricated to simulate clinical reconstruction and soaked in a vancomycin solution (50 mg/mL) for in vitro and in vivo testing. Three methicillin-resistant clinical isolates from human periprosthetic Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus lugdunensis knee infections were evaluated. In vitro testing assessed vancomycin loading capacity, mechanical properties, antibacterial activity, and inhibition of biofilm formation. For in vivo experiments, plain or vancomycin-loaded mesh was implanted into C57BL/6 mouse extensor mechanisms, which were intraoperatively contaminated with 1 of the 3 study isolates (5 per group). Mesh and surrounding tissue were harvested for quantitative culture on postoperative day 9. Results: For all 3 isolates, vancomycin-loaded mesh produced zones of inhibition and exhibited antibacterial activity through at least 3 days in vitro (p < 0.0001). Mechanical testing revealed that loading mesh with vancomycin did not negatively impact tensile strength, hysteresis, or suture pull-through properties. In vitro testing of inhibition of biofilm formation demonstrated reduced colony-forming units 6 hours after inoculation, which remained low throughout the 9-day experimental period (p < 0.05 for all isolates). In vivo, vancomycin-loaded mesh reduced bacterial burden on mesh and in surrounding tissue by >3 log 10 compared with plain mesh for all 3 isolates (p < 0.01 for both mesh and tissue). Conclusions: Vancomycin-loaded mesh provided in vitro antibacterial activity without compromising mesh mechanical properties and reduced staphylococcal infection in a murine EMR model. Further work is needed to evaluate translational potential and safety before clinical application. Clinical Relevance: Mesh-associated infection after EMR is devastating and difficult to treat. These preclinical findings suggest that local vancomycin delivery may serve as an adjunct to systemic prophylaxis, warranting further study before clinical use.

Endocrine therapy remains the cornerstone of treatment for estrogen receptor alpha (ERα)-positive breast cancer, yet the relationship between individual genetic background and molecular response to ERα-targeted therapy remains incompletely understood. Using a well-characterized panel of lymphoblastoid cell lines (LCLs), we performed genome-wide pharmacogenomic expression quantitative trait locus (PGx-eQTL) analysis to identify estradiol (E2)- and tamoxifen (TAM)-induced SNP-gene pairs. PGx-eQTL signals were integrated with previously published breast cancer genome-wide association study datasets to examine their association with clinically relevant breast cancer phenotypes. We identified two ER-mediated PGx-eQTL SNP-gene pairs associated with breast cancer prognosis post-treatment with E2 or TAM. Notable loci included E2-regulated MRPL15 and TAM-regulated SYCP3, which have effects in a genotype-dependent manner, with genotype-dependent survival outcomes, from worse to better relapse-free survival. Similar endocrine-therapy effects on patient survival and breast cancer risk were observed in SIK2, post TAM-treatment, and in LSM4 with E2-treatment. Moreover, qRT-PCR validation in an independent LCL panel confirmed the genotype-specificity of these signals. Overall, we identified ER-mediated PGx-eQTL SNP-gene pairs which represent potential pharmacogenomic tools for identifying patients likely to benefit from ERα-targeted endocrine therapy, offering a foundation for more genotype-informed individualized treatment decisions in breast cancer.

Photoplethysmography (PPG) is a non-invasive optical technique commonly used to measure heart rate and oxygen saturation, but its waveform contains additional physiological information that can be analyzed using artificial intelligence (AI). This narrative review summarizes the emerging applications of AI-based PPG in cardiovascular, respiratory, sleep, hemodynamic, pregnancy-related, and portal-hypertension assessment, with the aim of evaluating its potential beyond conventional monitoring and identifying barriers to clinical translation. The literature search was conducted using PubMed, Google Scholar, IEEE Xplore, ScienceDirect, and SpringerLink. Additional relevant studies were identified through screening the reference lists of included articles. Studies published between 2002 and 2026 were identified to capture the development of PPG from conventional monitoring to newer AI-based applications. Human studies were prioritized, while relevant computational, simulated, synthetic, ex vivo, and technical studies were also included. Studies unrelated to PPG, duplicates, and studies with limited relevance were excluded. A total of 96 references were included, covering AI approaches such as convolutional and deep neural networks, ensemble methods, transfer learning, U-Net, generative adversarial networks, and Transformer-based models. Overall, the reviewed evidence suggests that AI-based PPG may support blood pressure estimation, atrial fibrillation detection, sleep and respiratory monitoring, vascular aging assessment, pulmonary hypertension screening, preeclampsia assessment, volume-status and compensatory-reserve assessment, and exploratory assessment related to portal hypertension. However, clinical translation remains limited by motion artifacts, sensor and measurement-site variability, skin-pigmentation-related bias, physiological and environmental influences, heterogeneous methods, limited external validation, and inconsistent clinical and regulatory standards.

Abstract Circumscribed meningeal melanocytic neoplasms (CMMNs) represent a spectrum of rare central nervous system (CNS) tumors. Knowledge of their clinical behavior and molecular correlates remains limited. In this single‐institution retrospective study, we analyzed 31 patients (14 male, 17 female; median age, 59 years) diagnosed with CMMN between 2004 and 2025. In this patient cohort, based on the current World Health Organization Central Nervous System Tumor Classification (WHO CNS5) criteria, the majority of cases (18, 58.1%) fell into the intermediate‐grade melanocytic tumor (IMT) category based on histology, with either increased mitotic activity, CNS invasion, or both; 7 (22.6%) were melanocytomas, 5 (16.1%) melanomas, and 1 (3.2%) indeterminate case because of limited tissue. By next‐generation sequencing, mutations were identified in GNAQ/GNA11 in 21/24 cases, BAP1 in 5/23 (2 IMT, 3 melanoma), EIF1AX in 9/21 (1 melanocytoma, 8 IMT), and SF3B1 in 3/23 (2 IMT, 1 melanoma). Primary sites were spinal (20), posterior fossa (6), and supratentorial (5). During follow‐up, progression was observed in 5/6 melanocytomas, 9/13 IMTs, and 4/5 melanomas, suggesting a high frequency of progression across all groups. Two‐year progression‐free survival was 83.3% (95% confidence interval [CI], 53.5%–100.0%) for melanocytoma, 55.9% (95% CI, 26.7%–85.2%) for IMT, and 25.0% (95% CI, 0.0%–67.4%) for melanoma. Five‐year overall survival (OS) was 80.0% (95% CI, 44.9%–100.0%) for melanocytoma, 65.3% (95% CI, 37.0%–93.6%) for IMT, and 0.0% for melanoma. OS was significantly worse in melanoma compared with melanocytoma ( p = 0.002). BAP1 mutation correlated with worse OS (hazard ratio 8.73, p = 0.006). Upfront maximal safe resection appeared to be associated with improved outcomes in selected patients, whereas radiotherapy and systemic therapy did not demonstrate clear additional benefit in this cohort. In summary, our study shows that all CMMNs, irrespective of grade, have a high propensity to recur and melanoma histology and BAP1 mutation are associated with significantly worse OS.

ABSTRACT Background Pulsed field ablation (PFA) is an emerging non‐thermal ablation modality with proven safety in atrial arrhythmia ablation. However, data on its performance for ventricular arrhythmias (VA) remain limited. Objective To evaluate the feasibility, safety, and efficacy of PFA for complex VA in a multicenter real‐world US registry. Methods This retrospective study included consecutive patients undergoing PFA for ventricular tachycardia (VT) or premature ventricular contractions (PVCs) at three Mayo Clinic centers (April 2024 to July 2025). The primary feasibility outcome was the successful delivery of PFA lesions to the intended target substrate. Primary efficacy outcomes included acute procedural success; sustained VT recurrence requiring implantable cardioverter‐defibrillator (ICD) shocks or multiple antitachycardia pacing therapies; and ≥ 80% reduction in PVC burden. Safety outcomes included procedural complications, valvular function, thromboembolic events, renal function, and conduction disturbances. Results Twenty‐six patients were included (13 PVC, 13 VT). Acute success was achieved in all VT ablations (69.2% complete; 30.8% partial) and in 92.3% of PVC ablations. Complications occurred in 11.5% of patients (transient LBBB [ n = 1] and vascular complications [ n = 2]). No thromboembolic events, intracardiac thrombus, or acute kidney injury were observed. Lesions near the mitral valve apparatus did not worsen mitral regurgitation, including in patients with pre‐existing valve disease. After a median follow‐up of 365 days, one patient experienced VT recurrence requiring ICD shocks. Estimated recurrence‐free survival after VT ablation was 61.5% at 12 months; 58.3% of PVC patients achieved ≥ 80% burden reduction. Conclusion PFA for VA appears feasible and acutely effective, with a low rate of procedure‐related complications. While acute success was high, long‐term outcomes were acceptable for VT ablation and relatively modest for PVC ablation, highlighting the need for continued refinement of technology and energy‐delivery strategies. Larger prospective studies are warranted.

Abstract Gross brain findings help guide differential diagnosis, but their diagnostic value across major neurodegenerative diseases remains incompletely characterized. We evaluated whether gross descriptions in autopsy reports could classify cases by final neuropathologic diagnosis. We analyzed 5,613 autopsy cases from the Mayo Clinic Brain Bank collected between 1998 and 2023, including seven diagnostic categories: Alzheimer disease (AD), Lewy body disease (LBD), combined AD and LBD (AD-LBD), frontotemporal lobar degeneration, corticobasal degeneration, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). A fine-tuned large language model (LLM) converted narrative gross descriptions into semi-quantitative scores for 39 features. Extraction accuracy was 0.95 in 200 manually annotated feature-level test examples. A CatBoost classifier used the extracted scores as input, whereas a second fine-tuned LLM used standardized textual descriptions of the same features. Both classifiers also included age at death, sex, and brain weight. Performance was evaluated in the same held-out test set of 562 cases. CatBoost achieved an accuracy of 0.73, a Cohen’s kappa of 0.65, and a macro-average area under the receiver operating characteristic curve of 0.92. The text-based LLM achieved an accuracy of 0.75 and a kappa of 0.68. Macro-average sensitivity was 0.66 for both models. PSP sensitivity was 0.92 with CatBoost and 0.93 with text-based LLM. Corresponding sensitivities were 0.87 and 0.92 for MSA, but only 0.21 and 0.03 for AD-LBD. Feature attribution analysis identified subthalamic nucleus atrophy and putaminal abnormalities as contributors to PSP and MSA predictions, respectively. Narrative gross descriptions contained diagnostic information, particularly for disorders with distinctive macroscopic patterns, whereas combined AD-LBD remained difficult to distinguish.