A pilot randomized controlled trial of endovascular coils and vascular plugs for proximal splenic artery embolization in high-grade splenic trauma.

PURPOSE: To evaluate the feasibility of enrolling patients in a randomized controlled trial (RCT) comparing endovascular coils (EC) and vascular plugs (VP) for proximal splenic artery embolization (pSAE) in high-grade splenic trauma, and to collect data to inform the design of a larger clinical effectiveness trial. METHODS: Single-center, prospective, RCT of patients with Grade III-V splenic injuries selected for nonoperative management. Patients were randomized to pSAE with EC or VP. The main outcome was feasibility. We also evaluated technical success, time to stasis, complications, mortality, and splenectomy rates, by estimating rates and 95% confidence intervals. RESULTS: 46 of 50 eligible patients were enrolled (92%, 95% CI 90-100%). Overall, splenic salvage was 98% (45/46; 95% CI 94-100%). Primary technical success was observed in 22 EC patients (96%; 95% CI 87-100%) and 20 VP patients (87%; 95% CI 73-100%). Bayesian analysis suggests a > 80% probability that primary technical success is higher for EC. Two complications (one major and one minor) occurred in the EC group (9%; CI 0-20%) and one major complication occurred in the VP group (4%; CI 0-13%). CONCLUSIONS: Randomized comparisons of endovascular devices used for pSAE after trauma are feasible. pSAE using either EC or VP results in excellent rates of splenic salvage in trauma patients with high-grade splenic injuries. These high rates of splenic salvage and low rates of complications make their use as a primary outcome in a future trial problematic. Consideration should be given to technical parameters as a primary outcome for future trials.

Endovascular Management of Neurofibromatosis Type I-Associated Vasculopathy: A Case Series and Brief Review of the Literature.

PURPOSE: Neurofibromatosis type 1 (NF1) is an autosomal-dominant disorder found in approximately 1 of every 3000 individuals. Neurofibromatosis type 1 can have vascular manifestations including aneurysms, stenoses, and arteriovenous malformations. The purpose of this article is to describe the clinical manifestations of NF1 vasculopathy, discuss therapeutic options, and highlight endovascular therapies from our institutional experience. MATERIALS AND METHODS: The radiology information system was searched for cases of NF1. Cases with vasculopathy managed with endovascular therapies were included. Demographics, clinical histories, procedural details, and outcomes were recorded. A review of the literature for the management strategies of NF1 vasculopathy was performed. RESULTS: Two pediatric patients with NF1 were identified, both of whom presented with hypertension found to be secondary to renal artery stenosis. One of the patients also had infrarenal aortic narrowing. Both patients were successfully treated with balloon angioplasty, resulting in improved blood pressures. The review of the literature identified case series of pharmacologic, surgical, and endovascular therapies, although, endovascular therapies appear to be preferred due to lower morbidity and mortality. CONCLUSIONS: NF1 vasculopathy is a rare condition that most often presents with hypertension due to renal artery stenosis. In these situations, endovascular management is the preferred approach.

Effect of a dedicated inferior vena cava filter retrieval program on retrieval rates and number of patients lost to follow-up.

PURPOSE We aimed to assess the efficacy of a dedicated inferior vena cava (IVC) filter retrieval program on filter retrieval rates and number of patients lost to follow-up. METHODS A dedicated IVC filter retrieval program began in July 2016. This consisted of tracking all patients with retrievable filters placed by interventional radiology (IR). At the time of filter placement, patients were scheduled for a retrieval consult in the IR clinic. Any missed appointments were followed up by a physician assistant. The program was overseen by a single IR physician. To assess this program's efficacy, we reviewed the records of all patients who had retrievable IVC filters placed by IR nine months prior to and nine months after program initiation. Demographics and clinical factors were then collected and compared. A P value of < 0.05 was considered statistically significant. RESULTS Prior to the program, 76 patients (31 males, 45 females; mean age, 64.2 years) had retrievable filters placed; 75% were placed due to a contraindication to anticoagulation. From this group, five filters were removed (6.6%), 42 patients were lost to follow-up (55.3%), 22 patients died (29.0%), and seven filters were deemed permanent by a physician after placement (9.2%). All five retrievals were successful and no complications were reported. After program initiation, 106 patients (59 males, 47 females; mean age, 58.8 years) had retrievable filters placed; 75.5% were placed due to a contraindication to anticoagulation. In this group, 30 filters were retrieved (retrieval rate 28.3%), 17 patients were lost to follow-up (16%), 23 patients died (21.7%), 28 filters were deemed permanent by a physician after placement (26.4%), and decisions were still pending in eight patients (7.5%). One patient (3.3%) had a minor complication during filter retrieval. Initiation of a filter retrieval program increased our retrieval rate (6.6% vs. 28.3%; P < 0.001) and reduced the number of patients with filters that were lost to follow-up (55.3% vs. 16%; P < 0.001). CONCLUSION Dedicated filter retrieval program is effective in increasing filter retrieval rates and decreasing the number of patients lost to follow-up.

Dural Septation on the Inner Surface of the Jugular Foramen: An Anatomical Study.

Introduction Preserving cranial nerve (CN) function during tumor removal at the jugular foramen is challenging. No anatomical study has better defined the relevant dural septations on the inner surface of the jugular foramen. This study was undertaken to elucidate this anatomy. Methods Fourteen cadaveric heads (28 sides) were dissected, and relationships of the meningeal coverings of the jugular foramen and adjacent CNs documented. A classification scheme was created to better describe the dural septations of the inner surface of the jugular foramen. Results Four types of dural septations were noted. Type I: 10 sides (36%) where a dural septation was seen between CNs IX anteriorly and X and XI posteriorly. Of these, the septum was ossified in 20%. Type II (32%) was defined as a jugular foramen with no dural septation. Type III (7%) was defined as septation between CNs IX and X anteriorly and XI posteriorly. Type IV (7 sides, 25%) or the chaotic form was defined as multiple septations within the jugular foramen that housed and divided CN rootlets. Conclusions The dural septations defined here can be used in future studies to help correlate operative strategy to meningeal morphology within the jugular foramen.

Venous drainage of the spine and spinal cord: a comprehensive review of its history, embryology, anatomy, physiology, and pathology.

Venous drainage of the spine and spinal cord is accomplished through a complex network of venous structures compartmentalized to intrinsic, extrinsic, and extradural systems. As the literature on this topic is scarce, the following review was performed to summarize the available literature into a single coherent format. The medical literature on the spinal venous system was reviewed using online sources as well as historical documents that were not available online in regard to history, embryology, anatomy, and physiology with a particular emphasis on the pathology affecting this system. The spinal venous system is complex and variable. Proper understanding of all aspects is critical for the management of the pathology that results from its failure.

Relationship between the pituitary stalk angle in prefixed, normal, and postfixed optic chiasmata: an anatomic study with microsurgical application.

BACKGROUND: The relationship between the optic apparatus and the skull base is important during approaches near the sella turcica. One relationship that dictates which approach is taken is whether the optic chiasm is prefixed or postfixed or in a "normal" location, (centered over the diaphragma sella). The relationship between the position of the chiasm and the angulation of the pituitary stalk has not been investigated. METHODS: Forty adult cadavers without intracranial pathology were dissected and parasagitally hemisected lateral to the sella turcica. The angulations between the pre- and postfixed and normal chiasm and the pituitary stalk were evaluated under magnification. Additionally, 50 MRIs performed among patients evaluating headache were analyzed for these relationships. RESULTS: For cadavers, the chiasm was prefixed in 7.5% (n = 3), normal in 85% (n = 34), and postfixed in 7.5% (n = 3). On imaging, the chiasm was prefixed in 4% (n = 2), normal in 88% (n = 44), and postfixed in 8 % (n = 4). For all, the relation between the type of chiasm and the pituitary stalk was more often (p < 0.05) 90° or greater for prefixed chiasmata and acute angles for normal or postfixed chiasmata. CONCLUSIONS: These data may assist skull base surgeons when approaching pathology near the optic chiasm and pituitary stalk.

Variation in one residue associated with the metal ion-dependent adhesion site regulates αIIbß3 integrin ligand binding affinity.

The Asp of the RGD motif of the ligand coordinates with the ß I domain metal ion dependent adhesion site (MIDAS) divalent cation, emphasizing the importance of the MIDAS in ligand binding. There appears to be two distinct groups of integrins that differ in their ligand binding affinity and adhesion ability. These differences may be due to a specific residue associated with the MIDAS, particularly the ß3 residue Ala(252) and corresponding Ala in the ß1 integrin compared to the analogous Asp residue in the ß2 and ß7 integrins. Interestingly, mutations in the adjacent to MIDAS (ADMIDAS) of integrins α4ß7 and αLß2 increased the binding and adhesion abilities compared to the wild-type, while the same mutations in the α2ß1, α5ß1, αVß3, and αIIbß3 integrins demonstrated decreased ligand binding and adhesion. We introduced a mutation in the αIIbß3 to convert this MIDAS associated Ala(252) to Asp. By combination of this mutant with mutations of one or two ADMIDAS residues, we studied the effects of this residue on ligand binding and adhesion. Then, we performed molecular dynamics simulations on the wild-type and mutant αIIbß3 integrin ß I domains, and investigated the dynamics of metal ion binding sites in different integrin-RGD complexes. We found that the tendency of calculated binding free energies was in excellent agreement with the experimental results, suggesting that the variation in this MIDAS associated residue accounts for the differences in ligand binding and adhesion among different integrins, and it accounts for the conflicting results of ADMIDAS mutations within different integrins. This study sheds more light on the role of the MIDAS associated residue pertaining to ligand binding and adhesion and suggests that this residue may play a pivotal role in integrin-mediated cell rolling and firm adhesion.

Alfred W. Adson (1887-1951): his contributions to surgery for tumors of the spine and spinal cord in the context of spinal tumor surgery in the late 19th and early 20th centuries.

Alfred W. Adson was a pioneer in the field of neurosurgery. He described operations for a variety of neurosurgical diseases and developed surgical instruments. Under his leadership the Section of Neurological Surgery at the Mayo Clinic was established and he functioned as its first chair. Adson's contributions to the understanding of spinal and spinal cord tumors are less well known. This article reviews related medical records and publications and sets his contributions in the context of the work of other important pioneers in spinal tumor surgery at the time.

Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy.

While glioblastoma multiforme (GBM) is the most common adult malignant brain tumor, GBMs in childhood represent less than 10% of pediatric malignant brain tumors and are phenotypically and molecularly distinct from adult GBMs. Similar to adult patients, outcomes for children with high-grade gliomas (HGGs) remain poor. Furthermore, the significant morbidity and mortality yielded by pediatric GBM is compounded by neurotoxicity for the developing brain caused by current therapies. Poor outcomes have been attributed to a subpopulation of chemotherapy and radiotherapy resistant cells, termed "glioma stem cells" (GSCs), "glioma progenitor cells," or "glioma-initiating cells," which have the ability to initiate and maintain the tumor and to repopulate the recurring tumor after conventional therapy. Future innovative therapies for pediatric HGG must be able to eradicate these therapy-resistant GSCs. Oncolytic herpes simplex viruses (oHSV), genetically engineered to be safe for normal cells and to express diverse foreign anti-tumor therapeutic genes, have been demonstrated in preclinical studies to infect and kill GSCs and tumor cells equally while sparing normal brain cells. In this review, we discuss the unique aspects of pediatric GSCs, including markers to identify them, the microenvironment they reside in, signaling pathways that regulate them, mechanisms of cellular resistance, and approaches to target GSCs, with a focus on the promising therapeutic, genetically engineered oHSV.

Mutagenesis studies of the ß I domain metal ion binding sites on integrin αVß3 ligand binding affinity.

Three divalent cation binding sites in the integrin ß I domain have been shown to regulate ligand binding and adhesion. However, the degree of ligand binding and adhesion varies among integrins. The αLß2 and α4ß7 integrins show an increase in ligand binding affinity and adhesion when one of their ADMIDAS (adjacent to MIDAS, or the metal ion-dependent adhesion site) residues is mutated. By contrast, the α2ß1, α5ß1, and αIIbß3 integrins show a decrease in binding affinity and adhesion when their ADMIDAS is mutated. Our study here indicated that integrin αVß3 had lower affinity when the ADMIDAS was mutated. By comparing the primary sequences of these integrin subunits, we propose that one residue associated with the MIDAS (ß3 Ala(252)) may account for these differences. In the ß1 integrin subunit, the corresponding residue is also Ala, whereas in both ß2 and ß7 integrin subunits, it is Asp. We mutated the ß3 residue Ala(252) to Asp and combined this mutant with mutations of one or two ADMIDAS residues. The mutant A252D showed reduced ligand binding affinity and adhesion. The ligand binding affinity and adhesion were increased when this A252D mutant was paired with mutations of one ADMIDAS residue. But when paired with mutations of two ADMIDAS residues the mutant nearly abolished ligand-binding ability, which was restored by the activating glycosylation mutation. Our study suggests that the variation of this residue contributes to the different ligand binding affinities and adhesion abilities among different integrin families.

Regulation of integrin αIIbß3 ligand binding and signaling by the metal ion binding sites in the ß I domain.

The ability of αIIbß3 to bind ligands and undergo outside-in signaling is regulated by three divalent cation binding sites in the ß I domain. Specifically, the metal ion-dependent adhesion site (MIDAS) and the synergistic metal binding site (SyMBS) are thought to be required for ligand binding due to their synergy between Ca(2+) and Mg(2+). The adjacent to MIDAS (ADMIDAS) is an important ligand binding regulatory site that also acts as a critical link between the ß I and hybrid domains for signaling. Mutations in this site have provided conflicting results for ligand binding and adhesion in different integrins. We have mutated the ß3 SyMBS and ADMIDAS. The SyMBS mutant abolished ligand binding and outside-in signaling, but when an activating glycosylation mutation in the αIIb Calf 2 domain was introduced, the ligand binding affinity and signaling were restored. Thus, the SyMBS is important but not absolutely required for integrin bidirectional signaling. The ADMIDAS mutants showed reduced ligand binding affinity and abolished outside-in signaling, and the activating glycosylation mutation could fully restore integrin signaling of the ADMIDAS mutant. We propose that the ADMIDAS ion stabilizes the low-affinity state when the integrin headpiece is in the closed conformation, whereas it stabilizes the high-affinity state when the headpiece is in the open conformation with the swung-out hybrid domain.