CD47 monoclonal antibodies (mAbs) activate tumor-associated macrophages (TAMs) in sarcomas to phagocytose and eliminate cancer cells. Though CD47 mAbs have entered clinical trials, diagnostic tests for monitoring therapy response in vivo are currently lacking. Ferumoxytol is an FDA-approved iron supplement which can be used “off label” as a contrast agent: the nanoparticle-based drug is phagocytosed by TAM and can be detected with magnetic resonance imaging (MRI). We evaluated if ferumoxytol-enhanced MRI can monitor TAM response to CD47 mAb therapy in osteosarcomas. Forty-eight osteosarcoma-bearing mice were treated with CD47 mAb or control IgG and underwent pre- and post-treatment ferumoxytol-MRI scans. Tumor enhancement, quantified as T2 relaxation times, was compared with the quantity of TAMs as determined by immunofluorescence microscopy and flow cytometry. Quantitative data were compared between experimental groups using exact two-sided Wilcoxon rank-sum tests. Compared to IgG-treated controls, CD47 mAb-treated tumors demonstrated significantly shortened T2 relaxation times on ferumoxytol-MRI scans (p < 0.01) and significantly increased F4/80+CD80+ M1 macrophages on histopathology (p < 0.01). CD47 mAb-treated F4/80+ macrophages demonstrated significantly augmented phagocytosis of ferumoxytol nanoparticles (p < 0.01). Thus, we conclude that ferumoxytol-MRI can detect TAM response to CD47 mAb in mouse models of osteosarcoma. The ferumoxytol-MRI imaging test could be immediately applied to monitor CD47 mAb therapies in clinical trials.

Ferumoxytol nanoparticles can be used for in vivo detection of stem cell transplants with MPI and provide quantitative information not attainable with MRI.

Glioblastoma (GBM) has a dismal prognosis. Evidence from preclinical tumor models and human trials indicates the role of GBM initiating cells (GIC) in GBM drug resistance. Here, we propose a new treatment option with tumor enzyme-activatable, combined therapeutic and diagnostic (theranostic) nanoparticles, which caused specific toxicity against GBM tumor cells and GICs. The theranostic cross-linked iron oxide nanoparticles (CLIO) were conjugated to a highly potent vascular disrupting agent (ICT) and secured with a matrix-metalloproteinase (MMP-14) cleavable peptide. Treatment with CLIO-ICT disrupted tumor vasculature of MMP-14 expressing GBM, induced GIC apoptosis and significantly impaired tumor growth. In addition, the iron core of CLIO-ICT enabled in vivo drug tracking with MR imaging. Treatment with CLIO-ICT plus temozolomide achieved tumor remission and significantly increased survival of human GBM bearing mice by more than 2 fold compared to treatment with temozolomide alone. Thus, we present a novel therapeutic strategy with significant impact on survival and great potential for clinical translation.

artilage defects due to trauma, degenerative arthritis, or inflammatory arthritis affect approximately one out of five adults and represent a major cause of pain and disability (1-3). Because cartilage defects do not heal spontaneously, interventions are needed to induce repair. Bone marrow-derived autologous mesenchymal stromal cells (MSCs) can differentiate into chondrocytes and have been implanted into cartilage defects to restore joint health (4). However, cartilage repair outcomes of matrix-associated stem cell implants (MASIs) in patients have been highly variable: While some investigators reported full-thickness hyaline cartilage regeneration (5,6), others reported a failure rate of up to 50% for MASIs (7,8). Limited cell transplant survival was identified as the most important obstacle for successful cartilage repair (9). An imaging test that could help predict MASI outcomes would greatly enhance our ability to develop more successful cell transplant procedures. MRI is the primary modality for cartilage imaging (10,11). However, MRI within the 1st few weeks after MASI cannot help distinguish between grafts that will and grafts that will not repair the underlying cartilage defect (9). To date, successful cartilage repair is diagnosed many months after MASI, on the basis of a reduction in cartilage defect size at morphologic MRI (10,11). Unfortunately, failed cartilage repair and scar formation are difficult to correct at that time. Timely detection of an impending graft failure could enable rescue interventions

The long‐term survival of osteosarcoma patients with metastatic or recurrent disease remains dismal, and new therapeutic options are urgently needed. The purpose of our study was to compare the efficacy of CD47 mAb plus doxorubicin combination therapy in mouse models of osteosarcoma with CD47 mAb and doxorubicin monotherapy. Forty‐eight NOD scid gamma (NSG) mice with intratibial MNNG/HOS tumors received CD47 mAb, doxorubicin, combination therapy, or control IgG treatment. Twenty‐four mice (n = 6 per group) underwent pre‐ and post‐treatment magnetic resonance imaging (MRI) scans with the macrophage marker ferumoxytol, bioluminescence imaging, and histological analysis. Tumor ferumoxytol enhancement, tumor flux, and tumor‐associated macrophages (TAM) density were compared between different groups using a one‐way ANOVA. Twenty‐four additional NSG mice underwent survival analyses with Kaplan–Meier curves and a log‐rank (Mantel–Cox) test. Intratibial osteosarcomas demonstrated significantly stronger ferumoxytol enhancement and significantly increased TAM quantities after CD47 mAb plus doxorubicin combination therapy compared to CD47 mAb (P = 0.02) and doxorubicin monotherapy (P = 0.001). Tumor‐bearing mice treated with CD47 mAb plus doxorubicin combination therapy demonstrated significantly reduced tumor size and prolonged survival compared to control groups that received CD47 mAb (P = 0.03), doxorubicin monotherapy (P = 0.01), and control IgG (P = 0.001). In conclusion, CD47 mAb plus doxorubicin therapy demonstrates an additive therapeutic effect in mouse models of osteosarcomas, which can be monitored with an immediately clinically applicable MRI technique.

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The 3D-printed spinal model can make freehand pedicle screw placement safer in severe spinal deformity cases with acceptable accuracy, and no neurological or vascular complications.

BACKGROUND Opioid requirements in the perioperative period in patients undergoing lumbar spine fusion surgery remain problematic. Although minimally invasive surgery (MIS) techniques have been developed, there still remain substantial challenges to reducing length of hospital stay (LOS) because of postoperative opioid requirements. OBJECTIVE To study the effect of implementing an enhanced recovery after surgery (ERAS) pathway in patients undergoing a 1-level MIS transforaminal lumbar interbody fusion (MIS TLIF) at our institution. METHODS We implemented an ERAS pathway in patients undergoing an elective single-level MIS TLIF for degenerative changes at a single institution. Consecutive patients were enrolled over a 20-mo period and compared with a pre-ERAS group prior to the implementation of the ERAS protocol. The primary outcome was LOS. Secondary outcomes included reduction in morphine milligram equivalent units (MME), pain scores, postoperative urinary retention (POUR), and incidence of postoperative delirium. Patients were compared using the chi-square and Welch's 2-sample t-tests. RESULTS A total of 299 patients were evaluated in this study: 87 in the ERAS group and 212 in the pre-ERAS group. In the ERAS group, there was a significant reduction in LOS (3.13 ± 1.53 vs 3.71 ± 2.07 d, P = .019), total admission MME (252.74 ± 317.38 vs 455.91 ± 498.78 MME, P = .001), and the number of patients with POUR (48.3% vs 65.6%, P = .008). There were no differences in pain scores. CONCLUSION This is the largest ERAS MIS fusion cohort published to date evaluating a single cohort of patients in a generalizable manner. This ERAS pathway has shown a substantial decrease in LOS and opioid requirements in the immediate perioperative and postoperative period. There is further work to be done to evaluate patients undergoing other complex spine surgical interventions.