Citations

ABSTRACT Aging reshapes the architecture of human skeletal muscle, yet objective tissue‐level markers that capture this process remain limited. We combined large‐scale histology with deep learning to identify reproducible features of muscle aging and to test their biological relevance. We analyzed 974 hematoxylin–eosin whole‐slide images from a population resource using a dual‐attention convolutional neural network and an independent Mask R‐CNN model to quantify nuclear size and density, verified by manual review. The classifier distinguished young from aged muscle with high accuracy (AUC 0.91; accuracy 86.2%), and attention maps consistently highlighted nuclear enlargement and spatial disorganization as salient features. Nuclear diameter increased with age (Spearman's ρ = 0.71, p < 0.0001) across automated and manual measurements. Transcriptomes matched to the same donors showed that samples with larger nuclei were enriched for pathways related to chromatin remodeling, proteostasis, cellular senescence, mitochondrial activity, and telomere regulation, whereas smaller nuclei aligned with anti‐inflammatory and DNA repair programs. External pediatric inflammatory myopathies exhibited nuclear enlargement comparable to aged muscle, suggesting inflammation‐related premature histologic aging. These findings identify nuclear enlargement as a robust, quantifiable feature that integrates structural and molecular signatures of muscle aging. The proposed deep learning–based nuclear morphometry provides a scalable framework for tissue‐level aging biomarkers and suggests a potential “muscle aging clock” applicable to both physiological aging and disease states.

The NCCN Guidelines for Melanoma: Cutaneous provide strategies for the diagnosis, treatment, and follow-up of patients with cutaneous melanoma, which is among the most common cancers in the United States. The outcome of cutaneous melanoma is significantly influenced by stage at initial presentation. Generally, localized disease and smaller primary tumors have been associated with more favorable prognosis. Thus, the select content featured in this issue focuses on risk factors associated with cutaneous melanoma development and which should be considered during an initial assessment. These include (1) phenotypic predispositions, (2) personal medical history or comorbidities, (3) genetic predispositions, and (4) environmental factors.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues. It is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths from leukemias in the United States. 1 The NCCN Guidelines Panel for AML convenes annually to update recommendations for the diagnosis and treatment of AML in adults. These recommendations are based on a review of recently published clinical trials that have led to significant improvements in treatment or have yielded new information regarding biologic factors that may have prognostic importance. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding the monitoring and management of measurable (minimal) residual disease.

The International Academy for Clinical Hematology (IACH) is a global, non-profit educational organization dedicated to advancing excellence, equity, and innovation in clinical hematology. Since its creation, the IACH has built an international community spanning more than 130 countries, leveraging digital-first education, scientific collaboration, and professional networking to improve patient care worldwide. This document presents the IACH Strategic Vision for 2026–2030, outlining a structured roadmap for the Academy’s next phase of growth and international leadership. The strategy is built upon six interdependent pillars: scientific excellence and credibility; digital leadership and intelligent learning; academic alliances and global footprint; innovation, visibility, and advocacy; transparency and sustainability; and brand positioning with global impact. By reinforcing scientific rigor, embracing digital transformation, and promoting innovation, the IACH aims to become the most trusted global reference for clinical hematology education and collaboration. This strategic vision positions the IACH as a unifying platform to unite the world hematology community under one banner of knowledge, collaboration, and compassion, for the benefit of every patient, everywhere.

Myeloid sarcoma (MS) is a tumor mass involving any extramedullary site composed of myeloid-lineage blasts with myeloid, myelomonocytic, or monocytic differentiation. Distinguishing MS from malignant histiocytic neoplasms (MHNs) is diagnostically challenging due to morphologic and immunophenotypic overlap, particularly for MS with monocytic differentiation, which can mimic MHNs, especially the subtypes of histiocytic sarcoma and interdigitating dendritic cell sarcoma, leading to potential misdiagnosis and inappropriate management. Cyclin D1 overexpression is implicated in MHNs, but its utility in differentiating these entities has not been systematically characterized. We evaluated cyclin D1 immunostaining in 43 MS cases and 30 MHNs. The median age at MS diagnosis was 59 years (range: 0.1 to 90), while the median age at MHN diagnosis was 62 years (range: 9 to 90), with heterogeneous sites of involvement. Cyclin D1 evaluation showed 100% MHNs with strong cyclin D1 positivity in ≥50% tumor cells, compared with 7% MS with weak-to-intermediate positivity in a minor subset of tumor cells. Additional immunohistochemical evaluation showed no difference in PU.1 expression in MHNs (93%) versus MS (84%) but demonstrated a higher proportion of OCT2-positivity in MHNs over MS (52% vs. 23%, P <0.05). Our study demonstrates a high sensitivity (100%) and specificity (93%) in utilizing cyclin D1 to distinguish MHNs (mature phenotype) from MS (immature phenotype) in diagnostic practice. It is particularly valuable in challenging scenarios of MS with the absence of immature/myeloid lineage-defining markers (MPO, CD34, or CD117) and provides a cost-effective tool to resolve this diagnostic pitfall, ensuring an accurate subclassification.

Abstract Aims This study aimed to identify clinical factors associated with AVC in individuals with T2D. Methods and results This cross-sectional study is a pre-specified substudy of the multicentre randomized Steno INTEN-CT trial (Clinical Trials—INTEN-CT). Participants were eligible if they had T2D without ischaemic heart disease and were aged between 55–69 years (men) or 60–74 years (women). All participants underwent non-contrast cardiac computed tomography. AVC was measured in Agatston Units and categorized as 0, 0–300, ≥ 300. Of the 4570 participants, 46% had AVC &gt; 0. With increasing AVC, patients were older, predominantly males, and with significantly more comorbidities. In multivariable ordered logistic regression age (OR per SD 1.54, 95% CI 1.43–1.66), BMI (OR per SD 1.18, 95% CI 1.11–1.25), hypertension (OR 1.21, 95% CI 1.05–1.40), and chronic kidney disease (OR 1.18, 95% CI 1.03–1.36) were associated with higher AVC. Statin use was also associated with higher AVC (OR 1.50, 95% CI 1.27–1.78). Higher LDL cholesterol showed stronger associations with AVC in men than women (OR 1.39, 95% CI 1.24–1.56 vs. OR 1.16, 95% CI 1.02–1.31, P for interaction = 0.025). T2D severity (Haemoglobin A1c, T2D duration, and number of antidiabetic drugs) was not associated with AVC. Conclusion In individuals with T2D without cardiovascular disease, AVC is prevalent in nearly half of all individuals. Higher AVC was associated with T2D-related comorbidities, but not T2D severity.