Anti-CD47 antibody is effective for treating malignant pediatric brain tumors without detectable toxicity in patient-derived xenograft models.

Lymphedema is a common debilitating condition with very limited treatment options, and leukotriene B₄may be a key pathogenic molecule and therapeutic target.

Brain tumors are among the most lethal tumors. Glioblastoma, the most frequent primary brain tumor in adults, has a median survival time of approximately 15 months after diagnosis or a five-year survival rate of 10%; the recurrence rate is nearly 90%. Unfortunately, this prognosis has not improved for several decades. The lack of progress in the treatment of brain tumors has been attributed to their high rate of primary therapy resistance. Challenges such as pronounced inter-patient variability, intratumoral heterogeneity, and drug delivery across the blood–brain barrier hinder progress. A comprehensive, multiscale understanding of the disease, from the molecular to the whole tumor level, is needed to address the intratumor heterogeneity resulting from the coexistence of a diversity of neoplastic and non-neoplastic cell types in the tumor tissue. By contrast, inter-patient variability must be addressed by subtyping brain tumors to stratify patients and identify the best-matched drug(s) and therapies for a particular patient or cohort of patients. Accomplishing these diverse tasks will require a new framework, one involving a systems perspective in assessing the immense complexity of brain tumors. This would in turn entail a shift in how clinical medicine interfaces with the rapidly advancing high-throughput (HTP) technologies that have enabled the omics-scale profiling of molecular features of brain tumors from the single-cell to the tissue level. However, several gaps must be closed before such a framework can fulfill the promise of precision and personalized medicine for brain tumors. Ultimately, the goal is to integrate seamlessly multiscale systems analyses of patient tumors and clinical medicine. Accomplishing this goal would facilitate the rational design of therapeutic strategies matched to the characteristics of patients and their tumors. Here, we discuss some of the technologies, methodologies, and computational tools that will facilitate the realization of this vision to practice.

BACKGROUND AND PURPOSE: Tumor location has been shown to be a significant prognostic factor in patients with glioblastoma. The purpose of this study was to characterize glioblastoma lesions by identifying MR imaging voxel-based tumor location features that are associated with tumor molecular profiles, patient characteristics, and clinical outcomes. MATERIALS AND METHODS: Preoperative T1 anatomic MR images of 384 patients with glioblastomas were obtained from 2 independent cohorts (n = 253 from the Stanford University Medical Center for training and n = 131 from The Cancer Genome Atlas for validation). An automated computational image-analysis pipeline was developed to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good (overall survival of >17 months) and poor (overall survival of <11 months) survival groups identified in the training cohort were used to classify patients in The Cancer Genome Atlas cohort into 2 brain-location groups, for which clinical features, messenger RNA expression, and copy number changes were compared to elucidate the biologic basis of tumors located in different brain regions. RESULTS: Tumors in the right occipitotemporal periventricular white matter were significantly associated with poor survival in both training and test cohorts (both, log-rank P < .05) and had larger tumor volume compared with tumors in other locations. Tumors in the right periatrial location were associated with hypoxia pathway enrichment and PDGFRA amplification, making them potential targets for subgroup-specific therapies. CONCLUSIONS: Voxel-based location in glioblastoma is associated with patient outcome and may have a potential role for guiding personalized treatment.

Middle meningeal artery embolization (MMAE) is an established treatment option for chronic subdural hematoma. The aim of this systematic review and meta-analysis was to establish estimates of the pooled incidence for complications following MMAE. PubMed, Embase, and Cochrane were searched for studies reporting complications following MMAE through January 2023. A random effects model was used to calculate the pooled incidence of complications stratified based on whether studies excluded patients with comorbidities. Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed. A final 34 studies containing 921 patients undergoing MMAE were included that reported 35 complications. Neurological complications were reported in 7 studies with an overall pooled incidence of 3.8% (95% confidence interval [CI]: 2.6%-5.5%). Across these studies, there was a pooled incidence of 4.9% (95% CI: 2.9%-8.0%), 3.0% (95% CI: 1.7%-5.3%), and 2.1% (95% CI: 0.4%-9.7%) in studies that did not exclude, did not mention, or excluded patients with comorbidities, respectively. Similarly, 7 studies reported cardiovascular complications with an overall pooled incidence of 3.6% (95% CI: 2.4%-5.4%), 4 studies reported infectious complications with an overall pooled incidence of 2.9% (95% CI: 1.9%-4.5%), and 3 studies reported for miscellaneous complications with an overall pooled incidence of 3.1% (95% CI: 2.0%-4.8%). Further subgroup analysis revealed the pooled incidence of cardiovascular complications was 3.2% (95% CI: 1.7%-6.1%) in studies that did not exclude patients with comorbidities, 4.1% (95% CI: 2.3%-7.1%) in studies that did not specify the exclusion of such patients, and 1.8% (95% CI: 0.2%-11.5%) in studies that excluded these patients. Similarly, the incidence of infectious complications was 3.3% (95% CI: 1.7%-6.2%), 2.7% (95% CI: 1.5%-5.0%), and 1.8% (95% CI: 0.2%-11.5%) across these groups, respectively. Miscellaneous complications were reported at 4.0% (95% CI: 2.2%-7.2%), 2.3% (95% CI: 1.1%-4.6%), and 3.1% (95% CI: 0.9%-10.1%), respectively. The published literature suggests that MMAE is a generally well-tolerated procedure with a low risk of significant complications.