Citations

Background/Objectives: Characterizing spinal cord multiple sclerosis (MS) lesions in MRI is critical for diagnosis, monitoring, and treatment evaluation. However, current automated approaches for lesion detection and segmentation are typically designed for specific MRI contrasts or acquisition sites, limiting their generalizability in real-world clinical settings where imaging protocols vary widely. This work proposes a robust multi-site, multi-contrast segmentation framework for spinal cord lesions. Methods: The segmentation model was trained and evaluated on a large-scale dataset comprising 4428 annotated images from 1849 persons with MS across 23 imaging centers, encompassing six MRI contrasts (T1w, T2w, T2*w, PSIR, STIR, and UNIT1) acquired at 1.5 tesla (T), 3 T, and 7 T. Results: Likert-type assessment performed by neuroradiologist ratings demonstrated superior generalization of the model compared to existing contrast-specific pipelines ( p < 0.01). Additional experiments evaluated robustness across spinal levels, acquisition resolutions, binarization thresholds, and quantitative evaluation on external labeled datasets. Conclusions: The proposed model can achieve accurate and reliable spinal cord MS lesion segmentation across heterogeneous MRI data, addressing a key barrier to clinical translation. The model is available in the Spinal Cord Toolbox v7.2 and higher. Code repository: https://github.com/ivadomed/seg-sc-ms-lesion-multicontrast

ABSTRACT Background Retrospective evaluations of multidisciplinary team (MDT) review of pancreatic cystic lesions (PCL) demonstrate improved PCL management. Endoscopic ultrasound (EUS) evaluates PCL for worrisome features; however, its influence on MDT is unclear and may be attenuated by anchoring/confirmation bias. We aimed to evaluate the impact of EUS and the overall performance of MDT evaluation of PCL. Methods Four mock MDT sessions at two institutions were presented imaging from 40 consecutive PCL cases (20 “high‐risk” with advanced neoplasia, 20 “low‐risk” with pathologic low‐grade dysplasia or ≥ 3 years of non‐progression on surveillance), with and without upfront EUS/FNA (cytology, CEA, Amylase), in a randomized, crossover design. Group 1 adjudicated without EUS, Group 2 adjudicated with EUS, and Group 3 adjudicated with EUS after initially adjudicating without it. Results The cohort included branch‐duct ( n = 20), mixed type ( n = 6), and main duct ( n = 4) IPMN, MCN ( n = 5), and non‐mucinous PCL ( n = 5). Group 2 (EUS) correctly identified mucinous PCL with 97% sensitivity and 70% specificity, significantly higher than Group 1 (No EUS) (Sensitivity 91%, Specificity 20%; p = 0.04). Group 3 (Unblinded to EUS) performed significantly worse in mucinous PCL identification compared with Group 2, indicating cognitive bias (Sensitivity 97%, Specificity 10% ( p = 0.0003)). Group 2 correctly identified high‐risk PCL that required surgical intervention with 85% sensitivity and 85% specificity, significantly higher than Group 1 (Sensitivity 60%, Specificity 75%; p = 0.0016) and Group 3 (Sensitivity 73%, Specificity 80%, p = 0.0485). Conclusion While susceptible to cognitive bias, EUS significantly improves MDT assessment of PCL. MDT establishes a high bar for iterative additions of biomarkers to PCL analysis.

ABSTRACT Background Metabolic dysfunction‐associated steatotic liver disease (MASLD) exhibits marked heterogeneity in fibrosis progression and liver‐related outcomes. Liver biopsy is not feasible for longitudinal risk stratification at scale, creating a need for validated non‐invasive biomarkers, particularly imaging biomarkers, that can predict clinically meaningful disease progression and liver‐related outcomes. Aims To describe the design and rationale of the GOLDMINE study, established to determine whether non‐invasive imaging biomarkers predict MASLD progression and liver‐related clinical outcomes. Methods GOLDMINE is an investigator‐initiated, multi‐centre, international longitudinal cohort enrolling up to 1000 adults with either biopsy‐proven MASLD or MASLD cirrhosis across the full fibrosis spectrum. Participants are recruited from 15 sites in the US and 4 international sites (Japan, Singapore and France). At baseline, participants undergo clinical phenotyping, vibration‐controlled transient elastography, and advanced magnetic resonance imaging (MRI), including proton‐density‐fat‐fraction and magnetic resonance elastography (MRE). MRI (and biospecimen banking) is repeated at 2‐year intervals (years 2 and 4), with annual follow‐up visits for up to 10 years. Baseline liver histology is centrally processed, digitized and reviewed by a single expert hepatopathologist; all MRI/MREs are centrally interpreted. Results The prespecified clinical outcomes include progression to cirrhosis, clinically significant portal hypertension, major adverse liver‐related outcomes (ascites, hepatic encephalopathy, portal hypertensive bleeding, liver transplantation/qualification), hepatocellular carcinoma, major adverse cardiovascular events, and all‐cause mortality, with independent central adjudication of all events. Conclusions GOLDMINE establishes a rigorously phenotyped MASLD cohort integrating centralized histology, advanced MRI‐based biomarkers, longitudinal biobanking, and adjudicated outcomes, providing a platform to validate imaging and blood‐based prognostic biomarkers in MASLD.

Importance Brain imaging biomarkers may (1) identify underlying mechanisms of intervention effects and (2) define brain characteristics of those most likely to benefit cognitively from the intervention. Objective To test whether (1) a lifestyle intervention is related to brain changes, (2) brain changes are correlated with intervention-specific cognition changes, and (3) brain imaging biomarkers provide information about who is likely to benefit from a lifestyle intervention. Design, Setting, and Participants In this randomized clinical trial, the POINTER Imaging study was an ancillary study of the 2-year, single-blind multicenter US POINTER clinical trial in which neuroimaging data were collected on eligible enrolled participants. The study was conducted from May 2019 to March 2023 (final follow-up, May 14, 2025). Participants were enrolled into the POINTER Imaging study following a standard procedure at 5 clinical sites in the US. Participant eligibility criteria included an age of 60 to 79 years, sedentary lifestyle, and suboptimal diet, plus at least 2 additional risk criteria for cognitive decline and no contraindications for neuroimaging. Interventions Participants were randomly assigned to receive the structured or self-guided intervention. Both interventions emphasized increased physical and cognitive activity, healthy nutrition, social engagement, and cardiovascular health monitoring, but they differed in intensity and accountability. Main Outcomes and Measures There were 4 primary imaging outcomes: global β-amyloid (Aβ) burden, tau burden in the entorhinal cortex (ERC), hippocampal (HC) volume, and white matter hyperintensity volume. The primary cognitive measure was a global cognitive composite. Results Among 1943 parent trial participants who were assessed for eligibility, 983 underwent at least 1 magnetic resonance imaging or positron emission tomography scanning session. The mean (SD) age was 68.4 (5.2) years; 605 participants (61.5%) were female and 378 male (38.5%). Five hundred sixteen participants received the structured intervention and 467 the self-guided intervention. There were no intervention group differences in longitudinal cognitive or imaging outcomes. Intervention group differences were not associated with or moderated by Aβ status or accumulation. There was a negative association between change in ERC tau and change in global cognition in the self-guided group that was attenuated in the structured group (difference in association: 0.289; 95% CI, 0.029 to 0.550; interaction P = .03). Lower baseline HC volume was associated with greater cognitive benefit for participants in the structured group vs the self-guided group (lower HC: 0.077 SD; 95% CI, 0.022 to 0.132; higher HC: 0.002 SD; 95% CI, −0.037 to 0.041; interaction P = .03). Conclusion and Relevance This study found that a high-intensity multidomain lifestyle intervention did not affect brain biomarker trajectories and was not associated with Aβ pathology, but older adults with specific at-risk brain characteristics, including lower baseline HC volume, showed a greater cognitive benefit of the structured intervention. Trial Registration ClinicalTrials.gov Identifier: NCT03688126

Abstract Machine learning (ML) enables adaptive immune receptor repertoires (AIRRs) analyses for biomarker identification and therapeutic development. With the majority of AIRR data partially or imperfectly labeled, unsupervised ML is essential for motif discovery, biologically meaningful clustering, and generation of novel receptor sequences. However, no unified framework for unsupervised ML exists in the AIRR field, hindering the assessment of model robustness and generalizability. Here, we present an immuneML release advancing unsupervised ML in the AIRR field through unified clustering workflows, interpretable generative modeling, integration with protein language model embeddings, dimensionality reduction, and visualization. We demonstrate immuneML’s utility in three use cases: (i) benchmarking generative models for epitope-specific sequence generation, assessing specificity and novelty, (ii) systematic evaluation of clustering approaches on experimental receptor sequences against biological properties, such as epitope specificity and MHC, and (iii) unsupervised analysis of an experimental AIRR dataset to examine potential confounding, a practice widespread in related fields but unexplored in AIRR analyses.

Abstract Background Substituting group A whole blood (GAWB) might relieve some of the burden on the low titer group O whole blood (LTOWB) inventory. This simulation examined the effect of implementing GAWB at a large trauma hospital. Study Design and Methods A civilian trauma center with LTOWB and GAWB par levels set to 22 and 10 units, respectively, was modeled as the baseline. The average daily number of WB recipients was 0.5 who received an average of four WB units per patient. LTOWB was issued in packages of five and all had to be consumed before a group A patient could be switched to GAWB. Several variations on the baseline simulation were also modeled. Results In the baseline simulation, there was a median (interquartile range, IQR) of 1 (0–2) GAWB and 16 (13–19) LTOWB recipients per month. The median (IQR) GAWB and LTOWB units transfused per month was 2 (0–9) and 56 (42–72), respectively. Fourteen percent of group A patients received any quantity of GAWB. The variations that had the most impact on GAWB usage included increasing the number of WB recipients to 2.5 per day where the median (IQR) monthly number of GAWB recipients and units transfused increased to 4 (3–5) recipients and 21 (12–29) units, respectively, and when the average WB requirements increased to eight units per patient resulting in transfusing a median (IQR) of 10 (5–15) GAWB units per month to 3 (1–4) recipients. Discussion Under routine civilian hospital circumstances, implementing GAWB will have a modest impact on LTOWB inventory.

Abstract Background: Despite efficacy in metastatic clear cell renal cell carcinoma (ccRCC), immunotherapy currently has no role in the neoadjuvant setting. Suppressive tumor-associated macrophages (TAMs) are known to mediate resistance to immune checkpoint blockade (ICB) in ccRCC. In preclinical studies, IL-1β blockade reprograms TAMs toward an anti-tumor phenotype and promotes T cell activation, creating a tumor microenvironment (TME) more sensitive to ICB. To test this in patients, we conducted a correlative-rich neoadjuvant trial of IL-1β + PD-1 inhibition in localized ccRCC. Methods: SPARC-1 is a single-center, phase 1b study assessing the safety and feasibility of neoadjuvant canakinumab (αIL-1β) and spartalizumab (αPD-1) in patients with localized ccRCC (T1b-T4NanyM0 or TanyN1M0). All patients received 2 doses of canakinumab (300mg IV, Q4w) and spartalizumab (400mg IV, Q4w), 6 weeks (±7 days) prior to nephrectomy. The primary endpoint was safety and feasibility. Key secondary and exploratory endpoints included 12-month metastasis-free survival rate, pathologic response rate, and quantification of immune cell infiltration. To characterize immunologic reprogramming, fresh tumor specimens were collected at nephrectomy for single-cell RNA sequencing (scRNAseq) and multiparametric flow cytometry. Tissue from a treatment naïve cohort was collected for comparative analysis (n=16). Results: From August 15th, 2018, to January 30th, 2025, 14 patients were enrolled. There were no severe treatment-related adverse events (Grade ≥ 3) attributed to canakinumab or spartalizumab. At a median follow-up of 12.0 months (range, 6.3-12.0 months), the 12-month metastasis-free survival was 100%. Based on the ASSURE nomogram, the mean predicted 12-month recurrence risk was 16.7% (range, 4.7-46.5%). ScRNAseq revealed that treatment with αIL-1β + αPD-1 increased the frequency of TREM2+APOE+ TAMs (p=0.035), a population typically associated with immune suppression. However, these TAMs exhibited a phenotypic shift toward a less immunosuppressive state, with reduced IL-1β expression and increased CXCL9:SPP1 ratio, consistent with anti-tumor TAM polarization. Immune profiling revealed an increased CD8/CD4 T cell ratio (p=0.042) with modest enrichment of activated CD8+ T cells after treatment, supporting a more pro-inflammatory TME. Conclusions: The neoadjuvant combination of canakinumab (αIL-1β) and spartalizumab (αPD-1) is well-tolerated, feasible, and demonstrated promising clinical activity with no progression of disease observed in a localized ccRCC population at high risk of recurrence. Correlative analyses demonstrated that combined IL-1β and PD-1 blockade reprograms immunosuppressive TAMs, providing evidence that dual IL-1β and PD-1 inhibition can overcome myeloid-driven resistance in ccRCC. Clinical Trial Information: NCT04028245 Citation Format: Patrick J. McCann, Aleksandar Obradovic, Casey R. Ager, David H. Aggen, Catherine S. Spina, Chelsea L. Rahiman, Kaitlyn R. Campbell, Caroline Laplaca, Peyton C. Johnston, Amanda Kim, Katherine Gomez, Kriti Bagri Manjrekar, Mark N. Stein, Charles G. Drake, Karie Runcie, Matthew Dallos. Neoadjuvant IL-1β and PD-1 inhibition in localized clear-cell renal cell carcinoma: Clinical and correlative analyses of the phase 1b SPARC-1 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT017.

BACKGROUND AND OBJECTIVES: The prospective single-arm nonrandomized SCENT (Surpass Intracranial Aneurysm Embolization System Pivotal) trial on flow diverter treatment of large and giant intracranial aneurysms (IA) was analyzed for patients' age and IA characteristics affecting stroke and occlusion rates over 5 years (Trial registration NCT01716117). METHODS: Impact on major ipsilateral stroke and IA occlusion was studied by stratifying age as 65 years and younger vs older than 65. Kaplan–Meier estimates of time to both endpoints, stratified by age, were created. Univariate predictors of time-to-stroke were analyzed using univariable proportional hazards regression models. Limited bivariable modeling was also attempted. RESULTS: Of 180 patients with large or giant IA enrolled, 119 were 65 years and younger, whereas 61 were older than 65 years. The 3-year risk of stroke for the older than 65 years group (19.7%) was more than double that of the 65 years and younger group (9.2%), P = .047. No new strokes were reported between 3 and 5 years. Four patients (2.2%) experienced aneurysm rupture within the first week post-treatment, 3 being 65 years and younger and the fourth older than 65 (>.99). Complete IA occlusion within age strata at 1 year was: older than 65 60% (33/55), 65 years and younger 79.1% (87/110), P = .009, 3 years: older than 65 67.6% (25/37), 65 years and younger 82.5% (66/80), P = .071, and 5 years: older than 65 85.7% (18/21), 65 years and younger 91.8% (56/61), P = .417. CONCLUSION: Age older than 65 was associated with an increased risk of stroke and predictive of incomplete healing and increased time to healing.