Citations

Abstract INTRODUCTION Centiloid (CL) scaling standardizes amyloid positron emission tomography (PET) quantification across tracers and platforms; however, variability across software implementations may affect diagnostic classification. This study evaluated inter‐software variability and diagnostic performance across five platforms using identical 1 8 F‐florbetapir datasets. METHODS Retrospectively, 192 patients undergoing 1 8 F‐florbetapir PET/computed tomography (CT) and magnetic resonance imaging (MRI) were analyzed. CL values were generated using four US Food and Drug Administration (FDA) ‐cleared platforms and an in‐house Centiloid standard pipeline. Agreement was assessed using intraclass correlation coefficient, with bias and limits of agreement evaluated by linear modeling and Bland–Altman analysis. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and classification against visual interpretation. RESULTS Agreement was excellent (intraclass correlation coefficient [ICC] 0.969; 95%CI 0.961–0.975). Some platforms produced systematically higher CL values versus others slightly lower. LoA reached ± 30 CL. Diagnostic accuracy was high (area under the curve [AUC]: 0.949–0.975), with sensitivity 0.923–0.968 and specificity 0.667–0.806. DISCUSSION Despite excellent agreement, systematic differences persist and may affect classification near thresholds, supporting consistent use of a single processing pipeline.

BACKGROUND: Although diabetes is a known driver of heart failure with preserved ejection fraction, whether antecedent hyperinsulinemia drives preclinical diastolic dysfunction (DD) progression before overt hyperglycemia remains unknown. Therefore, we investigated whether elevated endogenous insulin and insulin resistance independently predict longitudinal DD progression and adverse cardiovascular outcomes. METHODS: In a community-based cohort study, we evaluated 1191 participants from the Olmsted County Heart Function Study (median age, 58.7 [interquartile range, 52.4–66.6 years]) who underwent echocardiography at baseline and after 4 years. Fasting insulin and homeostatic model assessment of insulin resistance were assessed. The primary end point was DD progression. Secondary outcomes (mortality, heart failure) were assessed in 2030 participants followed for a median of 10.97 (95% CI, 10.90–11.05) years for heart failure and a median of 18.1 (95% CI, 18.0–18.2) years for mortality. RESULTS: DD progression occurred in 7.5% of participants. Baseline fasting insulin and homeostatic model assessment of insulin resistance strongly predicted progression ( P <0.001). In multivariable analysis, every 1-SD increase in log-transformed insulin was associated with 65% increased odds of progression (odds ratio, 1.65 [95% CI, 1.33–2.07]; P <0.001), adjusting for age, creatinine, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Similar results were observed for homeostatic model assessment of insulin resistance (odds ratio, 1.66 [95% CI, 1.34–2.08]; P <0.001). In secondary analyses, elevated insulin independently predicted all-cause (hazard ratio, 1.11 per 1-SD [95% CI, 1.02–1.21]) and cardiovascular mortality (hazard ratio, 1.16 [95% CI, 1.02–1.33]). Homeostatic model assessment of insulin resistance was similarly predictive of all-cause (hazard ratio, 1.11 [95% CI, 1.03–1.20]) and cardiovascular mortality (hazard ratio, 1.16 [95% CI, 1.02–1.32]). CONCLUSIONS: Elevated endogenous insulin and insulin resistance are predictors of progressive DD and long-term mortality, even after accounting for body mass index. Metabolic dysregulation may drive myocardial stiffening before diabetes onset, identifying a potential early therapeutic window for heart failure with preserved ejection fraction prevention.

Background Prognostic staging systems in transthyretin amyloid (ATTR) cardiomyopathy were developed before the introduction of disease‐modifying treatment. We therefore evaluated contemporary risk stratification according to different staging systems in patients with ATTR cardiomyopathy. Methods All patients with newly diagnosed ATTR cardiomyopathy and baseline biomarker measurements from 2019 to 2023 were included from Mayo Clinic, Rochester, MN. Prognostic outcomes were calculated with Kaplan–Meier analysis for 3e staging systems in the main analysis: the National Amyloidosis Centre (NAC) staging system; a modified Mayo staging system using hsTNT (high‐sensitivity troponin T) cutoff >65 ng/L; the extended NAC model with a fourth stage (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide] >10 000 ng/L). Results The study population consisted of 441 patients with a median age of 76 years, 93% were men, 85% were initiated on tafamidis, and 94% had wild‐type ATTR. Median follow‐up was 3.4 years, and 109 deaths occurred during follow‐up. The 3‐year survival for the Mayo stages were 92.3% (88.7–95.9) for stage I, 71.6% (63.0–81.3) for stage II, and 43.5% (32.4–58.5) for stage III. For the NAC system, 3‐year survival were 92.0% (89.0–95.7), 67.5% (59.0–77.3), and 47.0% (34.7–63.5) for stages I, II, and III, respectively. The 3‐year survival by the extended NAC system was 92.0 (69.0–79.2), 69.0% (60.1–79.2), 53.2% (39.9–70.8) and 34.4% (17.4–68.0) for stages I, II, III, and IV, respectively. Conclusions In a contemporary cohort of patients with ATTR cardiomyopathy, the NAC and modified Mayo staging systems remained equally effective in delineating clinically meaningful prognostic groups, whereas the extended NAC system identified a stage IV subgroup with high mortality.

PURPOSE Cancer care capacity in sub-Saharan Africa (SSA) is constrained by late diagnosis and limited treatment access. Few funding mechanisms support innovative, locally led programs to address these challenges. A collaborative initiative was developed to strengthen oncology care through quality improvement (QI) projects. MATERIALS AND METHODS The program was developed by Global Bridges Oncology (GBO) at Mayo Clinic, Pfizer Global Medical Grants, and the African Organisation for Research and Training in Cancer. A committee composed primarily of African oncology experts guided the process. An RFP was disseminated across SSA in English, French, and Portuguese, inviting applications to improve diagnostic and therapeutic cancer care. Applications underwent a structured, two-stage review, with GBO providing technical support, expert guidance, and training resources. RESULTS The RFP generated 218 applications reflecting strong demand for oncology QI funding in SSA. After review, 17 projects representing 10 African countries were selected and awarded $1.1 million USD. Funded initiatives reflected four themes: oncology training and clinical practice improvements, early detection and accurate diagnostics, pediatric cancer care, and oncology nursing and palliative medicine. As of March 2026, 11 (65%) of 17 projects are complete, with 4,565 health care professionals engaged through direct training, conference dissemination, system adoption, and sensitization activities, and program-supported services were delivered to more than 47,300 patients. CONCLUSION This initiative demonstrates the feasibility of a competitive, regionally guided grant program to strengthen cancer care capacity. Early implementation outcomes, including measurable improvements in diagnostic delay, treatment adherence, and care network expansion, confirm that locally led QI initiatives can generate meaningful results across diverse institutional settings. By centering African leadership and supporting diverse QI projects, it advances equitable access to funding, capacity building, and sustainability planning.

ABSTRACT Biofilm‐associated staphylococcal infections remain exceptionally difficult to treat due to the presence of resilient staphylococcal biofilms and the limited effectiveness of currently available antibiotics. To combat persistent infections, providers are often forced to use prolonged courses of combination antimicrobial therapies that have significant toxicities with limited effectiveness, leading to increased hospital stays, substantial health care costs and a rise in patient morbidity and mortality. Staphylococcus aureus is a dominant cause of recalcitrant biofilms, for which novel non‐antibiotic therapeutics are critically needed. Lysins, a class of protein‐based antimicrobials, rapidly kill staphylococci, exhibit potent anti‐biofilm activity, have a low propensity of resistance development and synergy with antibiotics. To address this unmet need, we evaluate an extracellular vesicle (EV)‐based delivery platform for the engineered anti‐staphylococcal lysin LYSG101, designed to improve stability and localization at sites of infection. Initial proof‐of‐concept work is provided here, demonstrating that human serum‐derived EVs can be loaded with LYSG101 to exert a potent in vitro antimicrobial effect against both planktonic and biofilm forms of S. aureus . EV‐mediated delivery achieved activity equivalent to free lysin, with additional translational advantages including stability and the potential for sustained intra‐articular retention. This work supports further development of the EV‐mediated lysin delivery as a broadly applicable antimicrobial platform, with potential future applications in biofilm‐associated infections, including prosthetic joint infection (PJI).

Abstract Background Vagally mediated syncope and functional bradyarrhythmias can cause recurrent symptoms, injury and a need for permanent pacing, yet standard therapies do not address the underlying autonomic reflex. Cardioneuroablation (CNA) targets this mechanism, but adoption has been limited by uncertainty about patient selection, procedural endpoints and durable outcomes. Methods We studied 95 consecutive patients with vagally mediated syncope (n=78) or functional bradyarrhythmia (n=17) who underwent CNA at a single center by a single lead operator under a uniform, prospectively maintained protocol. Extracardiac vagal stimulation (ECVS) was performed before and after ablation to confirm vagally mediated sinus or atrioventricular (AV) nodal responses and to verify their attenuation. Outcomes through 1 year included clinical recurrence, quality of life, pacing burden and pacemaker extraction. Results Before ablation, ECVS provoked sinus pauses in 95.8% of patients and AV block in 91.6%; after ablation, sinus pauses were abolished in every patient and residual AV block was present in 4.2%. One-year freedom from recurrent syncope and from bradyarrhythmia-related events was 93.8% and 94.1%. Syncope burden fell from a median of 2.7 episodes per year to none, and disease-specific quality of life improved substantially (P<0.001). Among patients with pre-existing devices, atrial pacing burden fell from a median of 22% to 0%. There were no strokes, deaths or myocardial infarctions. Conclusions In this single-center cohort, physiology-guided CNA was associated with durable symptom control, improved quality of life and reduced pacing across vagally mediated bradyarrhythmia syndromes. Multicenter controlled studies are needed to confirm these findings.

Pediatric sarcomas are a heterogeneous group of rare mesodermal malignancies. These cancers, which affect children from infancy through adolescence and young adulthood, are in general challenging to treat with currently available therapies. Biologically, many are characterized by quiet genomes, fusion oncoproteins, immune “cold” microenvironments, and vast epigenetic deregulation that contributes to diverse and complex mechanistic drivers. Multifaceted advancements in research strategies, including high-throughput screening, new model systems, surfaceome profiling, and study of oncogenic fusion condensates have led to new opportunities for understanding the biology of pediatric sarcomas. To continue to make progress for these difficult to treat cancers, it will be critical to continue to improve access to bioinformatic data, approach patient care using innovative clinical trial frameworks, and foster interdisciplinary partnerships among medicinal chemists, scientists, clinicians, advocates, and industry partners.

Abstract Invasive lobular breast carcinoma (ILC) is the most common special histological subtype of breast cancer, which accounts for 10-15% of all cases. To study the phenotype characteristics, metastatic growth kinetic and immune microenvironment of ILC, we developed an orthotopically transplantable cell line model from the spontaneous mammary fat pad tumor of CDH1-PTEN dual knockout C57BL/6 mouse with Cre-loxP system, designated CPT6. CPT6 recapitulates single-file growth pattern of human ILC, with pleomorphic features and a high mitotic index. RNA sequencing together with whole exome sequencing reveals a luminal A subtype with targetable driver mutations such as Kras G12C. As a novel orthotopically transplantable ILC model in immune competent mice, CPT6 shows robust in vivo growth and metastatic rate, and has moderate immunogenicity which appears to be T-cell independent. We also profiled the immune microenvironment of CPT6, revealing a myeloid-rich environment with dominant M2-macrophage population, which is concordant with human ILC. In summary, this model recapitulates human ILC phenotype and represents a valuable preclinical platform for evaluating immunotherapy and other therapeutic strategies for invasive lobular breast carcinoma.

ABSTRACT Background Long‐term health effects of thymectomy in adults remain uncertain. Previous reports suggested associations with increased mortality, cancer incidence, and autoimmune disease, although these findings may reflect differences in patient selection, surgical indication, or follow‐up duration. We aimed to examine long‐term outcomes following adult thymectomy. Methods We performed a propensity score‐matched retrospective study of patients who underwent thymectomy or comparator cardiothoracic procedures, with follow‐up extending to 10 years. Primary outcomes were all‐cause mortality, new‐onset malignancy, and autoimmune disease. Findings were compared with those reported in a recent study that has raised caution regarding thymic excision. Results We identified 425 patients who underwent thymectomy and 5401 controls who underwent coronary artery bypass or valve surgery. After matching, 398 patients remained in each group. Thymectomy was not associated with increased mortality at 5 years ( HR = 0.63; 95% CI , 0.38–1.04) or 10 years ( HR = 0.78; 95% CI , 0.54–1.13). Excluding reclassified thymic cancers, 5‐year extrathymic malignancy incidence was 2.3% versus 1.8% ( p = 0.54); no significant differences were observed in immune‐related disease. Mortality was higher among patients with thymic malignancy. Among MG patients, only one event occurred, precluding reliable estimation. Conclusions Thymectomy was not associated with excess mortality or malignancy at 10 years compared with matched cardiothoracic controls. Indication‐stratified analyses within the thymectomy cohort showed higher mortality for thymic malignancy, with insufficient events to assess outcomes in MG patients. These findings do not support a generalized survival penalty from thymectomy, though caution is warranted for incidental thymic removal.

Medial ulnar collateral ligament (MUCL) injuries of the elbow have increased over the past 2 decades, particularly among adolescent and young adult overhead throwing athletes. Over time, operative techniques for MUCL injuries have evolved, with the goals of improving time to return and rates of return to sport and meeting athlete-specific demands. The purpose of this review is to evaluate the state of surgical management of MUCL injuries, assessing indications, techniques, and outcomes. Surgical techniques reviewed included MUCL-augmented repair with internal bracing, traditional reconstruction, reconstruction augmented with internal bracing, and revision MUCL reconstruction. While MUCL reconstruction has been the gold standard of treatment, augmented reconstruction and repair techniques have shown promising outcomes; these strategies emphasize anatomic restoration, preservation of native tissue, and individualized patient selection.