Citations

Abstract INTRODUCTION Glioblastoma is the most common malignant adult brain tumor with poor prognosis, largely due to its heterogeneous landscape. The AI-RANO and RANO-RGP groups organized the BraTS-Pathology 2024 challenge, providing a publicly-available dataset and a benchmarking environment for AI models to automatically identify six clinically-relevant histopathologic sub-regions in H&E-stained whole slide images (WSIs). METHODS We reclassified the TCGA-GBM and TCGA-LGG data according to the WHO 2021 criteria and identified diagnostic WSIs of 188 glioblastoma (IDH-wt, CNS WHO Gr.4) patients. A well-defined annotation protocol was communicated to eight neuropathologists, across eight institutions, who created “ground truth” annotations for Cellular Tumor (CT), Geographic Necrosis, Cortical Infiltration, Pseudopalisading Necrosis (PN), Microvascular Proliferation, and Penetration into White Matter (PWM). Comprehensive WSI curation for elimination of artifactual content and follow up partitioning resulted in approximately 300,000 data samples/patches. FINDINGS Inter-observer variability assessment highlighted difficulties in establishing a “gold standard”. The least annotated sub-regions (PWM and PN) were the most challenging to the participating methods, whereas all methods achieved their highest accuracy in the most annotated sub-region (CT). The highest average performance across sub-regions was obtained by a foundation model-based method. However, this top-ranked solution achieved an F1 score of 0.51 (Accuracy=0.65, Sensitivity=0.56, Specificity=0.93). CONCLUSIONS Our findings suggest that achieving state-of-the-art performance, in automatically identifying clinically-relevant glioblastoma sub-regions, remains an unsolved research problem. Analysis of the ground-truth annotations underscores the critical need for more precisely defined and neuropathologically standardized annotation protocol. Current AI algorithms are facing difficulties in addressing glioblastoma’s heterogeneous histologic landscape in the absence of large, comprehensively, and consistently annotated data. Building upon these findings, and towards developing more accurate AI algorithms, the 2025 iteration of the BraTS-Path challenge is currently on-going by leveraging two million data samples, aiming to enhance our disease understanding and improve diagnostic accuracy, ultimately contributing to improved patient outcomes.

ImportanceAtrial fibrillation (AF) is the most common, chronic, cardiac arrythmia in older US adults. It is not known whether AF is independently associated with increased risk of retinal stroke (central retinal artery occlusion), a subtype of ischemic stroke that causes severely disabling visual loss in most cases and is a harbinger of further vascular events.ObjectiveTo determine whether there is an association between AF and retinal stroke.Design, Setting, and ParticipantsThis retrospective cohort study was performed between July 2023 and May 2024 using computerized inpatient, outpatient, emergency department, and skilled nursing facility claims files for a 5% sample of US fee-for-service Medicare beneficiaries aged 66 years and older between 2000 and 2020. Follow-up ended at death, conclusion of fee-for-service Medicare coverage, end of the study period, or loss to follow-up of 85% of the study cohort.ExposureAF, based on validated International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes.Main Outcomes and MeasuresThe primary end point was incident retinal stroke in the primary diagnostic position of a single claim in any venue of care. Secondary end points included retinal stroke in any position of a single claim, 1 positive control end point (cerebral ischemic stroke), and 4 negative control end points (central retinal vein occlusion, urinary tract infection, humeral fracture, and cataract). Unadjusted and adjusted hazard ratios (HRs) and rate differences were computed across matched and overlap-weighted cohorts with and without AF (defined as 1 inpatient claim or 2 outpatient claims within a 365-day period).ResultsIn total, 1 090 144 patients (591 400 female [54.3%]; mean [SD] age, 76.92 [7.09] years) were included in the study; 545 072 patients had AF and 545 072 were matched controls. The median (IQR) follow-up was 45 (18 to 90) months. In total, 1333 patients with AF (rate, 0.55 per 1000 person-years) and 1082 AF-free matched controls (rate, 0.50 per 1000 person-years) experienced retinal stroke. The cause-specific, adjusted HR of retinal stroke after overlap weighting was 1.14 (95% CI, 1.02 to 1.28; adjusted rate difference, 0.05 [95% CI, −0.01 to 0.11]). AF was associated with cerebral ischemic stroke (adjusted HR, 1.73 [95% CI, 1.69 to 1.76]; adjusted rate difference, 10.11 [95% CI, 9.72 to 10.49]). Of 4 prespecified negative control end points, AF was not associated with central retinal vein occlusion but was associated with urinary tract infection, cataract, and humeral fracture.Conclusions and RelevanceIn this cohort study of Medicare beneficiaries aged 66 years and older, AF was independently associated with retinal stroke. The magnitude of the association was small, and a contribution from residual, unmeasured confounding could not be excluded.

Abstract Background We previously tested an intervention featuring educational outreach with modified academic detailing (AD) to increase anticoagulation (AC) use in patients with atrial fibrillation (AF). Currently, we compare providers receiving and not receiving AD in terms of inclusion of our AD educational topics and shared decision-making elements in documentation. Methods Physicians reviewed themes discussed with providers during AD and evaluated charts for evidence of shared decision-making. We then compared frequency of documentation of individual items for providers receiving AD compared with non-AD providers. To understand baseline documentation practices of AD providers, we also randomly selected encounters of AD providers before their AD participation. Results There were 113 eligible encounters in the four months after AD - 36 from AD providers and 77 from non-AD providers. We also identified 35 encounters from AD providers before participating in the intervention. Providers infrequently documented many reviewed items (% documenting): AC mentioned (44%), multiple options for AC (5%), CHA2DS2-VASc score (11%), bleeding risk factors (2%). Compared with non-AD providers, AD providers had statistically significant higher percentages for the following items: mention of AC (64% versus 35%), stroke risk (11% versus 0%), AC benefits (8% versus 0%), patient involvement (70% versus 0%). There was no improvement, however, for AD providers compared with baseline documentation percentages. Conclusions Providers infrequently documented important items in AC management and shared decision-making. AD participation did not improve documentation. Improving adoption of AD educational items may require more prolonged interaction with providers. Improving shared decision-making may require an intervention more focused on it and its documentation. Trial Registration The trial was registered as NCT03583008 on Clinicaltrials.gov on July 11, 2018.