Citations

Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune disease that predominantly affects the optic nerves and spinal cord, which is a distinct disease process from multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease. The most common neuro-ophthalmologic manifestation of NMOSD is atypical optic neuritis (ON), characterized by severe vision loss with a higher propensity toward bilateral involvement, longitudinal enhancement of the optic nerve, and chiasmal involvement than MS-related optic neuritis. Due to the severity of disease, high recurrence rate, and significant risk of permanent deficits, early recognition of neuro-ophthalmologic signs and short- and long-term management with immunosuppressive therapies is critical. In this article, we will review the characteristic neuro-ophthalmologic findings in NMOSD, serologic markers, neuroimaging findings, and current approaches to both acute and long-term treatment.

Abstract Geroscience research benefits from interdisciplinary approaches, team science, and collaborations, which collectively facilitate the discovery of aging mechanisms and their translation into tangible, clinical interventions. Since its inception in 2019, the Midwest Aging Consortium (MAC) has provided an engaging platform for aging researchers in the United States’ Midwest to connect, collaborate, and exchange ideas. The Sixth Annual Research Symposium of the MAC held at the Mayo Clinic in Rochester, Minnesota, in April 2025 highlighted the continued impact of the MAC in bringing together aging researchers, including many trainees and early career investigators, into a collaborative environment. This record-setting event featured interdisciplinary research on key aging mechanisms, including lipid metabolism, mitochondrial dysfunction, stress response, cellular senescence, and immune adaptations across organ systems. New therapeutic concepts and clinical trial approaches were presented. Cutting-edge methodologies including single-cell and spatial transcriptomics, metabolomics, and organoid cultures, to dissect aging process in tissue-specific and systemic contexts also were presented. Overall, the MAC symposium underscored the translational potential of geroscience and reinforced the MAC’s mission to accelerate aging research through regional collaborations and innovation.

Context.— Giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are rare but serious inflammatory heart diseases that pose significant diagnostic and therapeutic challenges. The relationship between the 2 has been debated for decades, sparked in part by a 1980 study using immunohistochemistry and electron microscopy to examine their histopathologic overlap. Objective.— To review and synthesize the historical, pathologic, clinical, and molecular understanding of GCM, explore its overlap and distinctions with CS, and outline future directions for diagnosis and treatment. Data Sources.— Historical literature, clinicopathologic studies, imaging studies, and molecular research including transcriptomic and proteomic analyses. Conclusions.— GCM is characterized by a fulminant clinical course, diffuse myocardial necrosis with multinucleated giant cells and eosinophilic infiltrate, and a predominantly CD8 + T-cell response. In contrast, CS typically presents with more indolent cardiac symptoms, well-formed nonnecrotizing granulomas with Langhans-type giant cells, and a CD4 + T-cell predominant response. GCM and CS share overlapping clinical and imaging features, and sometimes have histopathologic similarities as well. Emerging molecular data suggest transcriptional differences, but a subset of cases exhibit mixed or intermediate features, suggesting a possible disease spectrum. Advances in molecular profiling, standardized diagnostic criteria, noninvasive imaging modalities, and targeted immunosuppression may help refine diagnosis and treatment. Clarifying whether these conditions lie along a shared pathobiologic continuum remains an important goal for future research.

PURPOSE The feasibility of Oncotype DX Breast Recurrence Score testing on diagnostic core needle biopsy (CNB) samples has been demonstrated through analysis of a large central laboratory experience. However, concordance with paired samples from the same primary breast tumor has not been comprehensively evaluated. The primary objective of this study was to determine the degree of concordance of Recurrence Score (RS) results between paired CNB and surgical excision (SE) specimens from the same untreated primary breast tumor of patients with early-stage, hormone receptor–positive, human epidermal growth factor receptor 2–negative invasive breast cancer. MATERIALS AND METHODS Patients with a clinical RS result on either a CNB or SE specimen were included. Lin concordance correlation coefficient (CCC) with 95% CIs was estimated to assess agreement of continuous RS results between paired samples. Cohen Kappa with 95% CIs was used to evaluate categorical RS result concordance. RESULTS A total of 134 patients were identified with paired CNB and SE specimens. The median age was 62 years (range, 33-99; 23 patients [17%] were age ≤50 years v 111 [83%] age >50 years). The mean RS results were 15.6 (range, 0-56) for CNB and 16.6 (range, 0-59) for SE ( P = .003), with no statistically significant differences in RS categories. Agreement between continuous RS results from paired samples was strong, with a Lin CCC of 0.86 (95% CI, 0.80 to 0.90). The overall percent agreement in RS categories was 91.8% (95% CI, 87.1 to 96.4). Categorical agreement was further supported by a Cohen Kappa statistic of 0.64 (95% CI, 0.44 to 0.83), indicating substantial agreement between CNB and SE specimens. CONCLUSION The results of this study demonstrate high concordance of RS results between paired samples, which supports the use of CNB for Oncotype DX testing.

INTRODUCTION: A deeper understanding of the factors influencing survival in patients with pancreatic ductal adenocarcinoma (PDAC) is essential for optimizing treatment strategies. This study investigates the independent association of body composition parameters with overall survival in patients with PDAC. METHODS: This retrospective multisite cohort study included patients diagnosed with PDAC. Diagnostic computed tomography scans were retrieved, and body composition was evaluated using a validated deep learning-based segmentation algorithm that measured tissue volume and density in a 20 cm vertical abdominal section. RESULTS: A total of 1,666 patients with PDAC were included, 938 male (56.3%) and median age 69 years (interquartile range 61–76). In the subgroup of patients who underwent surgical resection (n = 509), myosteatosis (intramuscular infiltration of adipose tissue; hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.16–2.11, P = 0.004), sarcopenic obesity (HR 1.75, 95% CI 1.06–2.91, P = 0.03), and less subcutaneous adipose tissue (HR 1.09, 95% CI 1.03–1.16, P = 0.002) were associated with higher mortality. In patients receiving palliative systemic therapy (n = 439), lower skeletal muscle density (HR 1.43, 95% CI 1.03–1.99, P = 0.03) was associated with higher mortality. In patients who did not undergo tumor-targeted treatment (n = 718), less visceral adipose tissue (HR 1.04, 95% CI 1.01–1.08, P = 0.02) was associated with higher mortality. DISCUSSION: Body composition parameters, derived from computed tomography scans at the time of PDAC diagnosis, particularly low skeletal muscle density, sarcopenic obesity, and low adipose tissue, are independently associated with overall survival in patients with PDAC. Evaluating body composition at diagnosis could enhance clinical decision-making and enable more personalized treatment strategies.

Understanding the evolution of clinical tools and models of care is fundamental to advancing the field of epilepsy. The 2025 American Epilepsy Society Annual Course examined the expanding spectrum of epilepsy care through the integration of multispecialty collaboration, innovative diagnostic modalities, and surgical and nonsurgical therapeutic interventions. The course underscored significant global advancements in epilepsy research and practice. This comprehensive review synthesizes key educational insights from the program, offering a critical perspective on the ongoing transformation of epilepsy care.

Hearing loss is a highly prevalent disease state affecting almost 1 in 5 individuals globally. Growing research shows that untreated or undertreated hearing loss carries significant long-term sequelae, including increased risk of social isolation, depression, and cognitive decline, among other ramifications. Limited awareness and common misperceptions among the general US adult population and primary care providers contribute to low rates of referral to hearing specialty clinics and underutilization of hearing aids, cochlear implants, and other rehabilitative devices. Comprised of diverse membership, the Hearing Health Collaborative (HHC) was formed in May 2021 to identify and overcome challenges impacting good health care practices and public policy on hearing care in connection with healthy aging. This editorial documents a recent outcome of the HHC derived from a structured A3 process. Specifically, initiative 2, a proposal to develop a simple, clinically anchored staging system primarily for use by frontline providers and patients, is presented. Unlike other common disorders that harbor long-term health sequelae, a corresponding pragmatic clinical staging system—leveraging precedent disease staging convention, based on clinically meaningful outcomes and prognosis for acquired hearing loss—does not exist. The development of this staging system will potentially allow for improved communication across providers and patients, facilitate referral pathways, and ultimately enable patient access to timely and appropriate care.

This study proposes a novel two-dimensional Empirical Mode Decomposition (2D EMD)-based deep learning framework to enhance model performance in multi-class image classification tasks and potential early detection of diseases in healthcare using medical imaging. To validate this approach, we apply it to gastrointestinal (GI) endoscopic image classification using the publicly available Kvasir dataset, which contains eight GI image classes with 1000 images each. The proposed 2D EMD-based design procedure decomposes images into a full set of intrinsic mode functions (IMFs) to enhance image features beneficial for AI model development. Integrating 2D EMD into a deep learning pipeline, we evaluate its impact on four popular models (ResNet152, VGG19bn, MobileNetV3L, and SwinTransformerV2S). The results demonstrate that subtracting IMFs from the original image consistently improves accuracy, F1-score, and AUC for all models. The study reveals a notable enhancement in model performance, with an approximately 9% increase in accuracy compared to counterparts without EMD integration for ResNet152. Similarly, there is an increase of around 18% for VGG19L, 3% for MobileNetV3L, and 8% for SwinTransformerV2. Additionally, explainable AI (XAI) techniques, such as Grad-CAM, illustrate that the model focuses on GI regions for predictions. This study highlights the efficacy of 2D EMD in enhancing deep learning model performance for GI image classification, with potential applications in other domains.

Cisplatin is an imperative drug in the treatment of a wide range of cancers. However, it has various side effects including ototoxicity causing bilateral sensorineural hearing loss. Despite lacking a clearly defined mechanism, Reactive Oxygen Species (ROS) production and damage to Outer Hair Cells (OHCs) have been implicated as possible culprits. The ideal otoprotective drug would target inflammation and oxidative stress without compromising cisplatin’s efficacy. This study aimed to scrutinize whether intratympanic Epigallocatechin-3-Gallate (EGCG) exhibits a protective effect against cisplatin-related ototoxicity. Twenty-four adult male Wistar rats (8–10 weeks, 200–250 g) were randomly divided into four groups (n=6 per group): Cisplatin, EGCG, Cisplatin+EGCG, and Control. Cisplatin (15 mg/kg) was administered intraperitoneally, and/or EGCG (10 mg/mL, 200 μL) was injected transtympanically into the right ear, depending on group assignment. Control rats received intratympanic distilled water. After 72 h, auditory function was assessed by Auditory Brain Response (ABR), followed by histopathological and Signal Transducer and Activator of Transcription-1 (STAT1) immunohistochemistry evaluation of cochlear sections. All animals underwent baseline otoscopy and ABR to rule out pre-existing hearing impairment. Data were analyzed using repeated measures of Analysis of Variance (ANOVA) and paired t-tests for ABR thresholds, and Kruskal–Wallis/Mann–Whitney tests for histopathological and Immunohistochemistry (IHC) scoring. Statistical significance was defined as p <0.05. EGCG injections failed to prevent hearing threshold increases in the Cisplatin group. According to histopathologic and STAT-1 IHC evaluation in the treatment group, reduced OHC damage, apoptosis, and cochlear hyperemia were observed. Administration of EGCG alleviated apoptosis and prevented OHCs damage in animals. However, it could not prevent hearing loss significantly.