Citations

Abstract High-risk breast lesions (HRLs) encompass a heterogeneous group of pathologies that coexist with an adjacent or synchronous malignancy, confer an increased risk of future breast cancer, or warrant surgical consideration because of upgrade potential or local behavior. Despite their clinical importance, management of HRLs remains variable. The American Society of Breast Surgeons (ASBrS) and the Society of Breast Imaging are collaborating to establish unified, evidence-based guidelines for managing these lesions. While these recommendations are currently in development, this review summarizes the existing literature and current guidance, including ASBrS recommendations, to provide context for multidisciplinary management. The article reviews the histopathologic features, imaging appearance, and management strategies for HRLs, including atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), flat epithelial atypia (FEA), papillomas with and without atypia, radial scar/complex sclerosing lesion (RS/CSL), mucocele-like lesion (MLL), desmoid tumor, and pseudoangiomatous stromal hyperplasia (PASH). Recent literature supports nonoperative management for specific radiologic-pathologic concordant lesions, particularly limited ADH, pure FEA, and pure RS, highlighting the important role of multidisciplinary discussion for personalized care. Lesions such as LCIS subtypes, papilloma with atypia, and MLL with atypia continue to warrant excision due to higher reported upgrade rates to malignancy. Beyond short-term management, HRLs such as ADH, ALH, and LCIS serve as biomarkers of long-term breast cancer risk, informing recommendations for surveillance, risk assessment, and chemoprevention counseling. Achieving a consensus among radiology, pathology, and surgical disciplines is essential to ensure oncologic safety while minimizing overtreatment in the era of precision breast care.

Abstract Oncogenic BRAF alterations occur in a subset of diffuse gliomas across WHO grades and are increasingly identified through modern molecular diagnostics. In addition to standard glioma therapies, targeted treatments are available for patients with BRAF-altered glioma supported by variable evidence spanning randomized trials, single-arm studies, and real-world evidence. This joint consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO) synthesizes current knowledge on the diagnosis and management of BRAF-altered gliomas across age groups, tumor grades, and lines of therapy. Particular emphasis is placed on expert consensus in clinical scenarios where high-quality trial evidence remains limited. The review addresses rationale testing for BRAF alterations, selection, and monitoring of targeted therapies, management of treatment-related toxicities, approaches to resistance, and priorities for future research. It aims to provide practical, evidence-based guidance for clinicians while highlighting gaps to inform prospective studies.

Abstract Hepatic spheroids are widely used in bioartificial liver (BAL) systems, hepatotoxicology, and pharmacology due to improved functional stability compared with monolayer cultures. However, many existing methods rely on specialized equipment or static platforms that limit scalability and dynamic culture applications. Primary rat hepatocytes were cultured as three‐dimensional spheroids using a rocker‐based suspension system. Spheroid formation was evaluated across a range of rocking speeds (7–18 cycles per minute [cpm]) and inoculation densities. Spheroid morphology was quantified over time using two‐dimensional imaging. Functional performance was assessed by urea and albumin production on days 1, 4, 7, and 10. Spheroid formation efficiency was evaluated using volumetric modeling. Mean spheroid diameter decreased from 199 ± 41 μm at 7 cpm to 80.2 ± 17.6 μm at 18 cpm. The spheroid area was significantly influenced by both culture day ( p < 0.0001) and rocker speed, with significant differences observed across speeds at all time points ( p < 0.001, days 1–7). Mean spheroid area at 10 cpm was 13,750 ± 9051 μm 2 (day 1), 26,730 ± 8658 μm 2 (day 4), and decreased to 22,526 ± 8705 μm 2 (day 7). Urea production differed across speeds (ANOVA, p = 0.043), with peak performance at 12 cpm (median 3.47 μg/μg DNA) compared to 7 cpm (median 0.11 μg/μg DNA). Albumin production was 1086.8 ng/μg DNA on day 1 and 1534.4 ng/μg DNA on day 10. Urea production was 0.62 μg/μg DNA on day 1 and 1.25 μg/μg DNA on day 10. Median hepatocyte incorporation was 86% (range 73%–116%) by day 4. This rocker‐based method provides a simple, low‐cost, and scalable approach for generating hepatic spheroids with tunable size distributions under dynamic conditions. The system supports progressive functional maturation and is compatible with established scale‐up strategies, supporting its potential for translational applications.

Abstract The persistent global rise in atherosclerotic cardiovascular disease (ASCVD) challenges the effectiveness of current risk factor-based algorithms in primary prevention. Most myocardial infarctions occur in individuals without prior symptoms or recognized standard modifiable risk factors, underscoring the need to improve risk stratification. Coronary CT imaging, including coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA), enables direct non-invasive visualization of coronary atherosclerosis, supporting a shift from population-based prevention towards personalized, disease-based risk assessment and targeted preventive treatment. CCTA provides comprehensive evaluation of plaque burden, composition, stenosis severity, and high-risk plaque (HRP) features, thereby refining risk stratification and guiding personalized treatment decisions. The presence and total burden of coronary atherosclerotic plaque are considered the primary CCTA-derived markers for guiding preventive therapy, while noncalcified plaque burden and HRP features may support treatment intensification. Advances in CT technology, including photon-counting CT, and the application of artificial intelligence-based tools may further refine risk assessment by enabling accurate and reproducible plaque quantification and characterization. Although no randomized trials have yet demonstrated that CCTA-based screening improves clinical outcomes in asymptomatic individuals compared with standard care, the same is true of traditional cardiovascular risk scores. Three large ongoing randomized trials are currently evaluating whether CCTA-guided, personalized prevention strategies can reduce ASCVD events. The results are eagerly awaited and may redefine the role of CCTA in asymptomatic individuals.

Abstract This literature‐based systematic review and associated guidelines provide evidence‐based paradigms for the management of locoregionally recurrent rectal cancer (LRRC). This multispecialty committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and colorectal surgery. As is the standard, the previously described American Radium Society Appropriate Use Criteria methodology for this project was followed rigorously, with the Population, Intervention, Comparator, Outcome, Timing, and Study Design framework and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses methodology to assess the evidence. RAND/University of California Los Angeles consensus methodology (modified Delphi) was used to rate the appropriateness of treatment options. Published between January 1, 2013, and July 16, 2025, 116 peer‐reviewed trials provided the evidence: 10 were well‐designed randomized phase 2/3 trials, 29 were moderately well designed trials that accounted for most common biases (matched cohort and phase 2), 76 trials had design limitations (retrospective), and one was a meta‐analysis. Clinical cases were created as examples to illustrate current acceptable management of LRRC. Treatment and prognosis are influenced by prior therapy and the site(s) and extent of LRRC. The ability to achieve a margin‐negative surgical resection is the ultimate determinant of survival and local control. Preoperative systemic therapy, radiation therapy, or a combination of the two can facilitate tumor downsizing and improve the likelihood of a margin‐negative resection. An individualized multidisciplinary approach is required to ensure the best outcome. Although this review does not suggest a major alteration of current practice, it provides reassuring evidence of the importance of combined‐modality therapy.

Background/Objectives: Thoracic aortic aneurysm (TAA) often results from structural degeneration of the aortic wall. Traditional management focuses on hemodynamic control using beta-blockers (BB) and angiotensin receptor blockers (ARBs). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for diabetes and weight management, may offer additional vascular protective benefits through anti-inflammatory, antioxidative, and matrix-stabilizing mechanisms. However, their role in reducing mortality and thoracic aortic dissection (TAD) risk in patients with TAA has not been evaluated in human populations. In this study, we aimed to assess the association between GLP-1 RA use and the risks of mortality and thoracic aortic dissection. Methods: We conducted a retrospective cohort study of adults diagnosed with TAA between 2018 and 2024 across three Mayo Clinic sites. Patients receiving GLP-1 RAs were compared with non-users using 1:1 propensity score matching. Outcomes included all-cause mortality, cardiovascular mortality, and incident TAD. Kaplan–Meier and Cox proportional hazards analyses were performed. Results: A total of 32,279 patients with TAA, with a median age of 68.0 [IQR: 59.0–76.0] and 70.7% male, were included in a 1:1 propensity score match. This yielded a balanced cohort of 588 GLP-1 RA users and 588 non-users. Through a median follow-up of 4.1 (2.2, 5.9) years, GLP-1 RA use was associated with significantly lower 5-year cumulative incidence of all-cause mortality (5.0% vs. 14.5%, HR: 0.31; 95% CI: 0.19–0.50; p < 0.001), cardiovascular mortality (1.9% vs. 5.5%, HR: 0.30; 95% CI: 0.13–0.70; p = 0.005), and TAD (0.9% vs. 4.0%, HR: 0.19; 95% CI: 0.06–0.60; p < 0.0004). Conclusions: GLP-1 RAs are associated with reduced incidence of all-cause mortality, cardiovascular mortality, and TAD incidence in patients with TAA. Prospective studies are needed to confirm these findings and evaluate effects on aneurysm progression.

Abstract Exposure to asbestos is the primary cause of mesothelioma, however the processes underpinning its initiation and evolutionary trajectory remain elusive. To address this knowledge gap, we conducted whole exome sequencing and phylogenetic analysis of 277 mesotheliomas. Using multidimensional Dirichlet process clustering we inferred phylogenies, uncovering mutation order dominated by early 13q,1p, 8p, 6q and 22q somatic copy number alterations. Mesotheliomas exhibit a spectrum of genomic intra-tumor heterogeneity spanning linear (L) to highly branched (B) tree topologies, quantifiable by the Weighted Shannon Entropy (WSE). Somatic copy number alterations emerge earlier than single nucleotide variants (SNVs), and at a much faster relative rate in L-mesotheliomas. BAP1 is the only positively selected driver in L-mesotheliomas, whereas, B-mesotheliomas harbor multiple positively selected drivers and an aggressive phenotype, including a bias of loss of RPL5, and MTAP deletion linked to breakpoint enriched with long interspersed nuclear elements. L-trees had lower WSE, but greater T-cell inflammation and tertiary lymphoid structures, despite having a lower neoantigen burden. WSE is higher in larger volume, immunologically cold mesotheliomas, and is associated with shorter survival. In summary, progressive genomic heterogeneity is a defining feature of more aggressive mesothelioma yet illuminates opportunities for precision therapeutic intervention.

ABSTRACT Femoral nerve block is an essential regional anesthetic technique for surgery and analgesia of the anterior thigh, hip, and knee. Its effectiveness depends on understanding the femoral nerve's origin, branching pattern, fascial relationships, and common anatomical variations. This review summarizes current anatomical, cadaveric, and imaging studies to clarify the course of the femoral nerve and highlight variations such as high divisions, accessory branches, and vascular overlap that may influence block success. Approaches including landmark, nerve stimulator, and ultrasound‐guided techniques are reviewed with emphasis on procedural anatomy. Ultrasound features of the femoral nerve and fascia iliaca are correlated with cadaveric findings to outline optimal needle placement and spread of injectate. Continuous catheter methods, anesthetic selection, and volume considerations are also described. Comparative evidence indicates that ultrasound guidance improves accuracy, reduces vascular puncture, and decreases local anesthetic requirements compared with blind or stimulator‐based approaches. Clinical applications across orthopedic surgery, trauma care, and multimodal perioperative pathways are discussed, along with potential complications such as nerve injury, hematoma, systemic toxicity, and quadriceps weakness. Specifically, detailed knowledge of the femoral nerve's course beneath the fascia iliaca, its shifting proximity to the femoral vessels, and its variable early branching is the key to accurate needle placement, dependable block success, and fewer procedure‐related complications.

Tumor-associated antigens (TAAs) are non-mutated antigenic peptides expressed in cancer tissue at abnormally high levels but in normal tissue either at negligible levels, during only particular developmental stages, or in a tissue-restricted manner. The shared nature of TAAs across patients makes them attractive targets for off-the-shelf immunotherapies. However, no studies have comprehensively surveyed the TAA potential of all possible wild-type peptides originating from cancer-associated genes. In this study of 16 cancer tissue types and 39 normal tissue types, we analyzed the expression profiles of protein-coding genes to identify those with aberrantly high RNA levels across multiple solid tumor types and low RNA levels across all normal tissue types examined. We then developed a score to quantify tumor specificity of gene expression. Compared to previously reported TAA genes, those we identified exhibited substantially greater tumor specificity. Seven of these genes demonstrated consistently elevated expression in at least five tumor types and minimal expression across all non-immune-privileged normal tissues. To assess Human Leukocyte Antigen (HLA) class I presentation potential of the multi-cancer-associated genes, we computationally predicted the binding affinities between the most common class I HLA alleles and all possible wild-type TAA epitopes of 8–11 amino acids arising from those genes. We then applied rigorous filtering criteria to prioritize the most promising multi-cancer TAA peptide candidates and evaluated their HLA binding and cell-surface presentation using T2 and immunopeptidome analysis. Our results highlight new potential targets for multi-cancer immunotherapies.