Citations

Bone surface lesions include a variety of benign and malignant tumors and nonneoplastic entities, and knowledge of the different cell types and cortical bone surface anatomy equips radiologists to provide a useful differential diagnosis for these lesions.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hematopoietic Cell Transplantation (HCT) provide expert, multidisciplinary recommendations for autologous and allogeneic HCT based on current evidence. The NCCN Guidelines focus on pretransplant recipient evaluation, hematopoietic cell mobilization, conditioning, and the diagnosis and management of graft-versus-host disease (GVHD), a common complication of allogeneic HCT that is associated with significant morbidity. This selection from the NCCN Guidelines for HCT focuses on the diagnosis, workup, and management of acute and chronic GVHD, as well as important supportive care considerations.

Abstract BACKGROUND Volumetric analysis of brain metastatic lesions is of great relevance in neuro-oncology. Since manual annotation of a lesion is a laborious and time-consuming task, utilizing artificial intelligence (AI) tools for automated segmentation of brain metastases has shown promising potential, but published algorithms are not incorporated into clinical practice because of poor generalizability across institutions. Large publicly available and well-annotated datasets from across the world are critical for further clinical translation. MATERIAL AND METHODS The Brain Tumor Segmentation - Metastases (BraTS-METS) 2025 Lighthouse Challenge provides a competitive environment where scientists from various disciplines can benchmark their AI-based algorithms for automatic segmentation of pre- and post-treatment brain metastases on a well-curated publicly available brain metastasis dataset comprising 1,778 multiparametric brain MRI cases. Each case consists of T1-weighed, T1 post-contrast and FLAIR sequences. The cases were retrospectively obtained from 8 institutions in the USA and overseas, and underwent 3D nnU-Net pre-segmentation, followed by manual refinements performed by medical students and neuroradiologists, and a final approval by two independent board-certified neuroradiologists. A testing dataset was prepared through four rounds of annotation: two completed ‘from scratch’ and two following 3D nnU-Net pre-segmentation, all conducted by two independent neuroradiologists, with the segmentation process screen recorded for future analysis. This allowed us to establish inter- and intra-rater variability in brain metastases segmentation and create a reference standard dataset that will be publicly available after the conclusion of the challenge. The model performance of the participating teams in the challenge will be assessed via the following metrics: Dice Similarity Coefficient (DSC), Normalized Surface Distance (NSD), sensitivity, and precision of the model. RESULTS A multi-annotator testing dataset of 75 MRI cases of brain metastases and 300 segmentations (150 created ‘from scratch’ and 150 from 3D nnU-Net pre-segmentations of the cases) was developed as a new reference standard. The mean intra- and inter-rater DSC for the segmentations ‘from scratch’ were 0.68 and 0.59, respectively. The mean intra- and inter-rater DSC for the segmentations built upon 3D nnU-Net pre-segmentations were 0.88 and 0.77, respectively. CONCLUSION The BraTS-METS 2025 Lighthouse Challenge is a key initiative designed to advance the use of AI to improve characterization of brain metastases by providing algorithms for automatic segmentation of all lesions and peritumoral edema that are measured against a novel reference standard based on rigorous multi-annotator brain MRI segmentations.

Key Points Increased protein expression of tissue inhibitor of metalloproteinase-3, glypican 6, synuclein γ , apolipoprotein A-4, and Ecto-5′-nucleotidase was observed in old adults compared with young adults. In old adults, overexpressed proteins were enriched in mitochondrial processes while under expressed proteins enriched in RNA metabolism. Validated differentially expressed proteins were not significantly correlated with kidney pathology after adjusting for age. Background Kidney aging is characterized by a loss of glomeruli, predominantly in the superficial cortex, with a resultant decline in GFR and an increased risk of various kidney-related diseases. The early molecular alterations in glomeruli associated with the aging process are not well studied. Methods We combined laser capture microdissection and mass spectrometry–based unbiased proteomic analysis of nonsclerosed, nonischemic glomeruli in the superficial cortex from young and old adults who underwent a radical nephrectomy for a tumor to understand the age-related molecular changes in glomeruli. Twenty-four young and 30 old adults were used for the discovery dataset, and the significant differentially expressed proteins were further validated using an independent set comprising six young and eight old adults. Results Kidneys from old adults had lower eGFR, less kidney parenchyma on computed tomography imaging, and more glomerulosclerosis and arteriosclerosis on histology. Quantitative proteomic analysis of nonsclerosed, nonischemic glomeruli identified increased expression of tissue inhibitor of metalloproteinase-3, glypican 6, synuclein γ , apolipoprotein A-4, and Ecto-5′-nucleotidase in old adults that were further validated in an independent set. Pathway analysis indicated that proteins with increased expression in old adults were enriched in mitochondrial translational processes, aerobic respiration, and TCA cycle, whereas proteins with decreased expression in old adults were enriched in mRNA splicing, mRNA processing, and nonsense mediated decay. Furthermore, validated differentially expressed proteins did not show any significant correlation with the kidney pathology independent of age group. Conclusions Overall, this study identified proteins that are specifically associated with the aging process in otherwise normal-appearing glomeruli.

BACKGROUND AND OBJECTIVES: The therapeutic approach for small- and medium-sized vestibular schwannoma (VS) with normal hearing function remains controversial, with limited comparative data regarding hearing outcomes after stereotactic radiosurgery (SRS) or observation (OBS). We evaluated the serviceable hearing preservation, loss of American Academy of Otolaryngology-Head and Neck Surgery class A hearing, and tumor control (TC) across individuals with Koos grade I and II VSs and normal hearing at presentation who underwent SRS or OBS. METHODS: In this multicenter international study, we retrospectively analyzed the hearing, radiological, and neurological outcomes of patients who underwent SRS (SRS group) or OBS (OBS group). The cohorts were matched using propensity scores based on age, sex, tumor volume, pure-tone average, and speech discrimination score at a 1:1 ratio without replacement. RESULTS: After matching, each group comprised 57 patients. The median follow-up was 49 and 37 months for the SRS and the OBS groups, respectively ( P = .3). The 5- and 9-year serviceable hearing preservation rates in the SRS group were 76.2% and 42.4% vs 56.1% and 16.8% in the OBS group ( P = .17). Class A preservation occurred in 57.9% (33/57) of the SRS and 52.6% (30/57) of the OBS cohorts ( P = .70). Regarding the TC rates, SRS was associated with significantly higher TC rates ( P < .0001). CONCLUSION: We found that SRS is significantly superior regarding TC and provided noninferior hearing outcomes compared with OBS in VS patients with American Academy of Otolaryngology-Head and Neck Surgery class A hearing at presentation. Therefore, we suggest performing SRS in individuals with VS and normal hearing function.

Abstract We investigated the influence of 55 583 autophagy-related single-nucleotide polymorphisms (SNPs) on chronic lymphocytic leukemia (CLL) risk across 4 independent populations comprising 5472 CLL cases and 726 465 controls. We also examined their impact on overall survival (OS), time to first treatment (TTFT), autophagy flux, and immune responses. A meta-analysis of the 4 populations identified, to our knowledge, for the first time, significant associations between CDKN2A (rs3731204) and BCL2 (rs4940571, rs12457371, and rs1026825) SNPs and CLL risk, with CDKN2A showing the strongest association (P = 1.57 × 10−12). We also validated previously reported associations for FAS, BCL2, and BAK1 SNPs with CLL risk (P = 4.73 × 10−21 to 3.39 × 10−9). The CDKN2Ars3731204 and FASrs1926194 SNPs associated with increased CDKN2A and ACTA2 messenger RNA expression levels in the whole blood and/or lymphocytes (P = 5.1 × 10−7, P = 1.58 × 10−21, and P = 7.8 × 10−41), although no significant effect on autophagy flux was observed. However, associations were found between CDKN2A, BCL2, and FAS SNPs and various T-cell subsets, cytokine production, and circulating concentrations of interferon gamma, tumor necrosis factor–related apoptosis-inducing ligand, CD40, chemokine ligand 20, and interleukin-2 receptor subunit β proteins (P ≤ .005). No significant association was detected between autophagy variants and OS or TTFT, suggesting that these variants drive disease initiation rather than progression. In conclusion, this study identified 4 novel associations for CLL and provided insights into the biological pathways that influence CLL development.

BACKGROUND AND OBJECTIVES: Single-session stereotactic radiosurgery (SRS) has limited role for large arteriovenous malformations (AVM). Volume-staged SRS (VS-SRS) is used to optimize outcomes, but studies reporting results are limited. METHODS: This multicenter retrospective cohort of 378 patients from 21 centers reports results of VS-SRS for the entire AVM nidus. We report favorable outcome, obliteration, hemorrhage, and permanent symptomatic adverse radiation effect rates. RESULTS: The median age was 31 years (IQR: 19-44) at the first volume stage, with patients treated in 2–4 stages. The median total nidus volume was 21 cm 3 (IQR: 13.9-30.1 cm 3 ), and a median prescription dose of 17 Gy (IQR: 16-18 Gy) was used. The median radiographic and clinical follow-up were 48 and 55 months, respectively. Seventy-seven patients (20.4%) had a favorable outcome, with the 3-year and 5-year rates being 3.9% and 18%, respectively. 127 patients (33.6%) achieved obliteration, with the 3-year and 5-year rates being 6.8% and 26%, respectively. Obliteration rates of AVMs <15 cm 3 were 81% and 31%, respectively. The latency period hemorrhage incidence rate was 3.02 cases per 100 patient-years; 52 patients (13.8%) had a bleed. Seventy-two patients (19%) had symptomatic adverse radiation effect; in 38 patients (10.1%), these were permanent. Total nidus volume, prescription dose at first stage, diffuse nidus, and prior hemorrhage were all independent affecting outcome rates. CONCLUSION: VS-SRS can be used to treat large AVMs as a standalone treatment. Obliteration rates and favorable outcomes are lower than that with smaller AVMs, and repeat treatment is often required. Optimizing treatment plans, by increasing prescription doses, reducing treatment volume at each stage, and increasing the number of stages, may lead to better outcomes.

Background: Vascular endothelial growth factor inhibitors (VEGF-I) are frequently used for cancer treatment. VEGF-I can cause proteinuria and acute kidney injury (AKI) with thrombotic microangiopathy (TMA) as a commonly described pathology, but other glomerular pathologies are not well characterized. We aim to describe the clinical characteristics and glomerular lesions associated with VEFG-I in a single center cohort. Methods: We performed a retrospective chart review of patients treated with VEGF-I and underwent kidney biopsies from 2010 to 2022 at the Mayo Clinic, Rochester, MN. Biopsy findings were reviewed by our pathologists. Data on patients’ characteristics, clinical course, and outcomes were abstracted. Descriptive statistics were used to report relevant patient characteristics and findings. Results: From 2010 to 2022, 19 kidney biopsies were performed for kidney dysfunction in patients on VEGF-I. Eleven had complete data, with a median age of 62 years (interquartile range 58–66 years); renal cell carcinoma (RCC) was the most common cancer (4 of 11 patients). TMA was noted in 8 of the 11 biopsies, with proteinuria as the most frequent indication for biopsy in these cases. Three patients had findings other than TMA. One developed anti-phospholipase A2 receptor negative membranous nephropathy; VEGF-I and pembrolizumab were discontinued, and prednisone improved proteinuria. Another patient had known cryoglobulinemia with nephrotic range proteinuria which was exacerbated by VEGF-I peaking at 11 g/day. Despite stopping VEGF-I and treating with prednisone and rituximab, kidney dysfunction progressed to end stage kidney disease (ESKD). A third patient had IgA nephropathy with concurrent diabetic changes, but proteinuria progressed even after stopping VEGF-I. Conclusion: In this case-series of patients treated with VEGF-I undergoing kidney biopsy, we describe the pathological characteristics, clinical course, and outcomes of patients with pathologies other than TMA. Our study adds information to the sparse literature on patients with renal dysfunction after receiving VEGF-I.