Summary
Most organs are currently preserved by cold storage (CS) prior to transplantation. However, as more so called marginal donor organs are utilized, machine perfusion has regained clinical interest. Recent studies have demonstrated advantages of pulsatile perfusion over CS preservation for kidney transplantation. However, it remains unclear whether there is a significant benefit of one preservation method over the other in general, or, whether the utilization of particular preservation approaches needs to be linked to organ characteristics. Proposed protective mechanisms of pulsatile perfusion remain largely obscure. It can be speculated that pulsatile perfusion may not only provide nutrition and facilitate the elimination of toxins but also trigger protective mechanisms leading to the amelioration of innate immune responses. Those aspects may be of particular relevance when utilizing grafts with suboptimal quality which may have an increased vulnerability to ischemia/reperfusion injury and compromised repair mechanisms. This review aims to enunciate the principles of organ perfusion and preservation as they relate to indication, aspects of organ protection and to highlight future developments.
Tumor-associated macrophages (TAMs) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with noninvasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults. In a , Institutional Review Board-approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (two lymphoma and three bone sarcoma) underwent pre- and postcontrast MRI. Subsequently, 20 patients (10 lymphoma and 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24 to 48 hours after i.v. injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2* relaxation times of lymphomas and bone sarcomas. Tumor T2* values of 20 patients were correlated with CD68 and CD163 TAM quantities on histopathology. Significant ferumoxytol tumor enhancement was noted on postcontrast scans compared with precontrast scans ( = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density ( < 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68 and CD163 TAM ( < 0.05). Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies. .
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
Our streamlined ferumoxytol-enhanced PET/MR protocol provided cancer staging of children and young adults in less than 1 h with equivalent or superior clinical information compared to clinical standard staging tests. The detection of small pulmonary nodules with PET/MR needs to be improved.
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