Citations

Background: Accurate preoperative characterization of axillary lymph nodes (ALNs) is important in breast cancer, but conventional ultrasound has variable diagnostic performance. We evaluated quantitative shear wave elastography (SWE) for distinguishing reactive from metastatic ALNs, and we explored associations between nodal SWE parameters, breast cancer subtypes, and histological grades. Methods: We prospectively enrolled women with suspicious breast lesions and ALNs identified by clinical ultrasound who were scheduled for biopsy. After exclusions, 141 patients (57 reactive and 84 metastatic ALNs) were included. ElasticNet-regularized logistic regression with nested cross-validation compared clinical ultrasound alone with ultrasound plus SWE. Among 70 patients with metastatic ALNs and immunohistochemical characterization, SWE parameters were compared across surrogate subtypes and histological grades using Kruskal–Wallis tests with Holm adjustments. Results: The combined ultrasound–SWE model achieved an area under the receiver operating characteristic curve of 0.911 (95% CI, 0.859–0.961) compared to 0.798 (95% CI, 0.723–0.873) for ultrasound alone. At the Youden-derived threshold, the combined model achieved 88.1% sensitivity, 82.5% specificity, and 85.8% accuracy. Among metastatic ALNs, SWE parameters, namely Vmean, Vsd, and Vmax, differed significantly across surrogate subtypes, with the most pronounced differences observed between Luminal A and Luminal B tumors, (p = 0.0250, p = 0.0069, and p = 0.0065). No statistically significant differences were detected with histological grades in the five SWE parameters. Conclusions: Quantitative SWE complemented conventional ultrasound for assessing axillary nodal metastasis, with higher cross-validated discrimination for the combined model. Exploratory analyses identified differences in several SWE stiffness metrics between Luminal A and Luminal B tumors; these subtype-associated biomechanical differences require validation in larger cohorts.

ABSTRACT Among 9457 aquaporin‐4 (AQP4) immunoglobulin G‐positive patients, 2071 underwent autoimmune encephalitis antibody testing and 85 (4%) had coexisting antibodies, most commonly cerebrospinal fluid glial fibrillary acidic protein‐IgG and N‐methyl‐D‐aspartate receptor‐IgG, or serum high‐titer GAD65‐IgG. Compared with AQP4‐IgG positive neuromyelitis optica spectrum disorder controls, dual‐positive patients were younger and more frequently exhibited encephalopathy, psychiatric symptoms, seizures, ovarian teratomas, and deep gray matter, temporal lobe, or diencephalic MRI abnormalities. GAD65‐IgG‐positive patients developed stiff‐person syndrome. These findings define a distinct mixed glial‐neuronal autoimmune phenotype and support additional neural antibody testing in atypical AQP4‐IgG‐positive presentations.

Abstract Positron emission tomography (PET)-based molecular imaging is a clinically important tool for the evaluation of dementia and other neurodegenerative disorders, using radiotracers that target specific molecular and pathophysiological processes. Fluorodeoxyglucose brain PET has historically supported neurodegenerative disorder evaluation through detection of characteristic patterns of regional glucose hypometabolism. In recent years, the molecular imaging of protein aggregates has taken on an increasingly important role. This is evident with the widespread clinical adoption of amyloid PET and early use of tau PET to provide diagnostic and prognostic information for patients with suspected Alzheimer’s disease. Additional classes of radiotracers relevant to neurodegenerative diseases are under active investigation, including those targeting neuroinflammation, synaptic density, and α-synuclein aggregates. We review the major classes of PET radiotracers for neurodegenerative diseases, describing their molecular mechanisms, diagnostic performance, and their current and emerging clinical roles in dementia evaluation. Case examples for clinically used tracers illustrate imaging features relevant to diagnosis and characterization of prognosis and treatment effect. Finally, we discuss early developments and current challenges in the development of theranostic approaches and novel radiotracers for neurodegenerative diseases.

Background Obstructive sleep apnea (OSA)–chronic obstructive pulmonary disease overlap syndrome has been linked to worse cardiovascular outcomes. Preserved ratio impaired spirometry (PRISm) is recognized as an early stage of chronic obstructive pulmonary diseas. However, whether the coexistence of OSA and PRISm confers increased cardiovascular risk remains unknown. Methods Using data from the Sleep Heart Health Study, participants were categorized into 4 groups according to OSA and PRISm status. The primary outcome was major adverse cardiovascular and cerebrovascular events. The secondary outcome was cardiovascular disease mortality. Multivariable Cox regression models were used to evaluate the association of these groups with the risk of cardiovascular outcomes. Results During a median follow‐up of 11.45 years, the incidence of major adverse cardiovascular and cerebrovascular events was 17.00% in non‐OSA with normal lung function, 27.52% in non‐OSA with PRISm, 25.28% in OSA with normal lung function, and 49.40% in OSA with PRISm. After multivariable adjustment, compared with non‐OSA with normal lung function, the adjusted hazard ratios (HRs) for major adverse cardiovascular and cerebrovascular events were 1.20 (95% CI, 0.82–1.75) in non‐OSA with PRISm, 1.04 (95% CI, 0.89–1.21) in OSA with normal lung function, and 1.52 (95% CI, 1.08–2.12) in OSA with PRISm. Corresponding HRs for CVD mortality were 2.02 (95% CI, 1.26–3.24), 1.05 (95% CI, 0.81–1.35), and 2.17 (95% CI, 1.41–3.34), respectively. A significant sex interaction was observed ( P for interaction=0.009), with the association present only in women. Conclusions The coexistence of OSA and PRISm is independently associated with increased risk of adverse cardiovascular outcomes. This association is observed predominantly in women.

Systematic reviews of randomized controlled trials (RCTs) support evidence-based clinical advancement. Clinical trial reporting guidelines, including CONSORT, establish common data elements that support systematic synthesis of published trial outcomes. However, the rapid rise of digital health technologies presents new challenges for reporting guidelines, and substantial real-world reporting heterogeneity has been observed. Therefore, machine-assisted evaluation of reporting adherence offers a pathway for more agile information management to accommodate the diverse and disruptive nature of digital health technology-enabled RCTs. Here, we propose an accelerated retrieval-to-abstraction literature synthesis framework to conduct article screening, text and table data preprocessing, and full-text review using an unmodified pretrained large language model. We apply this methodology in two digital health technology-enabled RCT case studies evaluating adherence to technology and digital health equity guideline reporting items. Large language model performance was on par with inter-annotator agreement F1 scores (≥0.9) in both screening and information-extraction tasks. These findings support the scalability and rigor of accelerated evidence synthesis and demonstrate the importance of common reporting elements across digital health technology-enabled RCTs.

Abstract Glioblastoma (GBM) is a lethal, treatment-resistant brain cancer characterized by diffuse brain invasion, complex neuron-glioma signaling, and cellular, molecular, and spatial heterogeneity. Surgery is the current mainstay of treatment, aimed at maximizing tumor cytoreduction, decompressing the brain to improve neurological function, and providing material for analyses to inform prognostication and adjuvant treatment selection. To accurately model GBM surgical resection and tissue sampling in preclinical animal models, we developed the Maximal Safe Intracranial Surgery (MSIS) system. MSIS integrated a miniaturized neurosurgical resection device and enabled a safe, tunable, and reproducible approach for intracranial tumor resection, multi-regional biopsy, and longitudinal tissue sampling in murine models, with stereotactic, sterile, and high-viability tissue collection. MSIS was applied across five distinct orthotopic brain tumor models to reproducibly generate histologically and radiologically representative models of post-surgical GBM. Similar to humans, increasing the extent of resection correlated with improved animal survival, and recurrent growth patterns varied significantly by model type. Transcriptional profiles of matched primary vs. post-surgical recurrent tumors revealed enrichment of margin-associated transcriptional states consistent with neuron-glioma signaling. Overall, the MSIS system offers opportunities to model the standard-of-care, dissect the spatial and temporal dynamics of GBM, and pair therapeutic discovery with contextual tumor pathobiology.

Odontogenic myxoma (OM) is an uncommon, locally aggressive odontogenic neoplasm with characteristic histologic and clinico-radiographic features but with potential for histologic overlap with other odontogenic and non-odontogenic entities and a non-specific immunoprofile. Widespread loss of heterozygosity (LOH) has been recently described in rare cases of OM. The aim of this study was to determine whether widespread LOH represents a recurrent molecular signature that can be leveraged for clinical decision-making. Allele-specific copy number variation data from chromosomal microarray were generated from 7 OM, comprising a combined prospective and retrospective cohort. Four tumors arose in the mandible and 3 in the maxilla in patients ranging in age from 18 to 94 years (median: 44), with tumor size ranging from 2.2 to 13.0 cm. Variable amounts of fibrous stroma (odontogenic “fibromyxoma”) were present in 4/7 OM, and hypercellularity not typically appreciated in conventional OM was present in 3/7 cases. All OM (7/7) demonstrated widespread LOH, with 5 cases showing a near-haploid/low hypodiploid genomes (multiple monosomies) and 2 cases showing evidence of pseudo-hyperdiploidy due to probable endoreduplication. Both pseudo-hyperdiploid cases were ≥10 cm in size; 1 represented local recurrence. Chromosomes 1 to 3, 6, 9, 11, 13, 15, and 22 demonstrated LOH in ≥75% of cases (chromosomes 1 to 3, 6, and 9 in 100% of cases), while chromosomes 5, 12, 19, and 20 universally retained heterozygosity. Altogether, widespread LOH is a recurrent event in OM and a novel finding in odontogenic pathology, and allele-specific copy number variation analysis can serve as a diagnostic adjunct in challenging cases.