Clinical trials have proven oncolytic virotherapy to be safe but not effective. We have shown that oncolytic viruses (OV) injected into intracranial gliomas established in rodents are rapidly cleared, and this is associated with up-regulation of markers (CD68 and CD163) of cells of monocytic lineage (monocytes/microglia/macrophages). However, it is unclear whether these cells directly impede intratumoral persistence of OV through phagocytosis and whether they infiltrate the tumor from the blood or the brain parenchyma. To investigate this, we depleted phagocytes with clodronate liposomes (CL) in vivo through systemic delivery and ex vivo in brain slice models with gliomas. Interestingly, systemic CL depleted over 80% of peripheral CD163 + macrophages in animal spleen and peripheral blood, thereby decreasing intratumoral infiltration of these cells, but CD68 + cells were unchanged. Intratumoral viral titers increased 5-fold. In contrast, ex vivo CL depleted only CD68 + cells from brain slices, and intratumoral viral titers increased 10-fold. These data indicate that phagocytosis by both peripheral CD163 + and brain-resident CD68 + cells infiltrating tumor directly affects viral clearance from tumor. Thus, improved therapeutic efficacy may require modulation of these innate immune cells. In support of this new therapeutic paradigm, we observed intratumoral up-regulation of CD68 + and CD163 + cells following treatment with OV in a patient with glioblastoma. [Cancer Res 2007;67(19):9398-406]

Background: The ideal central venous catheter (CVC) tip position placement is controversial, and CVCs do not remain in a fixed position after placement. This study evaluates both patient and procedural factors which may influence CVC tip migration and subsequent catheter dysfunction. Materials and Methods: This study evaluates CVC placements at a single institution. Patient age, gender, body mass index (BMI), catheter laterality, CVC type and indication for central venous access were recorded. Catheter tip location relative to the carina was measured at time of placement and removal utilizing supine fluoroscopic imaging. Patients’ electronic medical records were reviewed for evidence of catheter dysfunction. Statistical analysis was performed utilizing odds ratios and two tailed Student’s t-test. Results: 177 patients were included (101 female; mean age 55; mean BMI 29.2). Catheter types included 122 ports, 50 tunneled large bore central venous catheters (≥9 French), and 5 tunneled small bore central venous catheters (<9 French). 127 were right sided catheters, and 50 were left sided. Left sided CVCs had a mean cranial tip migration of 3.2 cm (standard deviation ±2.9 cm) compared to 0.8 cm (standard deviation ±1.9 cm) for right sided catheters (p = 0.000008). Catheters that migrated cranially by >2 cm had more than 7× greater risk of dysfunction compared to catheters that migrated ≤2 cm (odds ratio of 7.2; p = 0.0001). Left sided CVCs were significantly more likely to have >2 cm of cranial migration (odds ratio 6.9, 95% CI 3.4–14.2, p < 0.0001) and had a higher rate of dysfunction, likely due to this cranial migration (32% vs. 4.7%; p = 0.00001). Gender and BMI were not found to be associated with catheter dysfunction or an increased odds ratio of >2 cm cranial migration. Conclusions: Left-sided CVCs migrate an average of 2.4 cm cranially more than right-sided catheters. Additionally, when migration occurs, left-sided catheters are more likely to be dysfunctional. These suggest that lower initial placement may be beneficial in left-sided catheters.

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Background and AimMesenchymal precursor cells (MPC) are reported to possess immunomodulatory properties that may prove beneficial in autoimmune and other inflammatory conditions. However, their mechanism of action is poorly understood. A collagen-induced arthritis model has been previously developed which demonstrates local joint inflammation and systemic inflammatory changes. These include not only increased levels of inflammatory markers, but also vascular endothelial cell dysfunction, characterised by reduced endothelium-dependent vasodilation. This study aimed to characterise the changes in systemic inflammatory markers and endothelial function following the intravenous administration of MPC, in the ovine model.MethodsArthritis was induced in sixteen adult sheep by administration of bovine type II collagen into the hock joint following initial sensitisation. After 24h, sheep were administered either 150 million allogeneic ovine MPCs intravenously, or saline only. Fibrinogen and serum amyloid-A were measured in plasma to assess systemic inflammation, along with pro-inflammatory and anti-inflammatory cytokines. Animals were necropsied two weeks following arthritis induction. Coronary and digital arterial segments were mounted in a Mulvaney-Halpern wire myograph. The relaxant response to endothelium-dependent and endothelium-independent vasodilators was used to assess endothelial dysfunction.Results and ConclusionArthritic sheep treated with MPC demonstrated a marked spike in plasma IL-10, 24h following MPC administration. They also showed significantly reduced plasma levels of the inflammatory markers, fibrinogen and serum amyloid A, and increased HDL. Coronary arteries from RA sheep treated with MPCs demonstrated a significantly greater maximal relaxation to bradykinin when compared to untreated RA sheep (253.6 ± 17.1% of pre-contracted tone vs. 182.3 ± 27.3% in controls), and digital arteries also demonstrated greater endothelium-dependent vasodilation. This study demonstrated that MPCs given intravenously are able to attenuate systemic inflammatory changes associated with a monoarthritis, including the development of endothelial dysfunction.

There is a lack of evidence or societal guidelines regarding the utility of fibrinogen monitoring during thrombolysis. The purpose of our study was to investigate the current use of monitoring fibrinogen levels during thrombolysis. A voluntary, anonymous online survey was sent to all physician members of the Society of Interventional Radiology, consisting of 23 questions related to practitioner demographics, thrombolysis protocol, and fibrinogen monitoring. There were 455 physician responses; 82% of respondents monitored fibrinogen levels during thrombolysis, of which 97% decreased or stopped tissue plasminogen activator based on the level. Self-reported estimates of significant bleeding events during thrombolysis were 1.86% in those who monitored fibrinogen and 1.93% in those who did not. Only 34% of all respondents report, in their clinical experience, having found low fibrinogen level to be correlated with bleeding events. There was no significant difference in self-reported major bleeding rates between practitioners who monitor and those who do not monitor fibrinogen. This high variability of clinical use of fibrinogen monitoring during catheter-directed thrombolysis is secondary to the paucity of scientific studies demonstrating its utility; further scientific investigation is needed to define the true utility of fibrinogen monitoring.

Morbidly adherent placentas are a spectrum of abnormalities ranging from placental invasion of the myometrium to invasion past the myometrium and muscular layers into adjacent structures. This entity is becoming more prevalent recently with increased number of cesarean deliveries. Given the high risk of morbidity and mortality, this was traditionally treated with pre-term planned cesarean hysterectomy. However, recently, uterine preservation techniques have been implemented for those women wishing to preserve future fertility or their uterus. Early identification is crucial as studies have shown better outcomes for women treated at tertiary care facilities by a dedicated multidisciplinary team. Interventional radiologists are frequently included in the care of these patients as there are several different endovascular techniques which can be implemented to decrease morbidity in these patients both in conjunction with cesarean hysterectomy and in the setting of uterine preservation. This article will review the spectrum of morbidly adherent placentas, imaging, as well as the surgical and endovascular interventions implemented in the care of these complex patients.

BackgroundThe purpose of this study was to investigate the therapeutic efficacy of intravenously administered immunoselected STRO-3 + mesenchymal precursor cells (MPCs) on clinical scores, joint pathology and cytokine production in an ovine model of monoarthritis.MethodsMonoarthritis was established in 16 adult merino sheep by administration of bovine type II collagen into the left hock joint following initial sensitization to this antigen. After 24 h, sheep were administered either 150 million allogeneic ovine MPCs (n = 8) or saline (n = 8) intravenously (IV). Lameness, joint swelling and pain were monitored and blood samples for leukocytes and cytokine levels were collected at intervals following arthritis induction. Animals were necropsied 14 days after arthritis induction and gross and histopathological evaluations were undertaken on tissues from the arthritic (left) and contralateral (right) joints.ResultsMPC-treated sheep demonstrated significantly reduced clinical signs of lameness, joint pain and swelling compared with saline controls. They also showed decreased cartilage erosions, synovial stromal cell activation and angiogenesis. This was accompanied by decreased infiltration of the synovial tissues by CD4+ lymphocytes and CD14+ monocytes/macrophages. Over the 3 days following joint arthropathy induction, the numbers of neutrophils circulating in the blood and plasma concentrations of activin A were significantly reduced in animals administered MPCs.ConclusionsThe results of this study have demonstrated the capacity of IV-administered MPCs to mitigate the clinical signs and some of the inflammatory mediators responsible for joint tissue destruction in a large animal model of monoarthritis.

Hereditary hemorrhagic telangiectasia (HHT) is a disorder that affects 1 in 5000–10,000 people worldwide and can result in devastating complications such as cerebral abscess, stroke, massive hemorrhage, and even death. HHT is an autosomal dominant disorder that leads to the formation of abnormal communication between the arteries and veins with a resultant spectrum of vascular anomalies. The disorder affects many organ systems and thus requires a dedicated multidisciplinary approach. Interventional radiologists are vital members of this team providing expertise not only in disease management, but in complex embolotherapy, helping to maintain the health of these patients. This article reviews clinical manifestations, screening guidelines, diagnostic criteria, and endovascular management of HHT.