A Review of Robotic Interventional Neuroradiology.

Robotic interventional neuroradiology is an emerging field with the potential to enhance patient safety, reduce occupational hazards, and expand systems of care. Endovascular robots allow the operator to precisely control guidewires and catheters from a lead-shielded cockpit located several feet (or potentially hundreds of miles) from the patient. This has opened up the possibility of expanding telestroke networks to patients without access to life-saving procedures such as stroke thrombectomy and cerebral aneurysm occlusion by highly-experienced physicians. The prototype machines, first developed in the early 2000s, have evolved into machines capable of a broad range of techniques, while incorporating newly automated maneuvers and safety algorithms. In recent years, preliminary clinical research has been published demonstrating the safety and feasibility of the technology in cerebral angiography and intracranial intervention. The next step is to conduct larger, multisite, prospective studies to assess generalizability and, ultimately, improve patient outcomes in neurovascular disease.

Lesion stability characteristics outperform degree of stenosis in predicting outcomes following stenting for symptomatic intracranial atherosclerosis.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) causes substantial morbidity and mortality. Treatment decisions have most commonly been driven by the degree of luminal stenosis. This study compares ICAD lesion stability features with percentage stenosis for associations with adverse outcomes following treatment with stents. MATERIALS AND METHODS: Retrospective analysis was performed of prospectively maintained procedure logs. Lesions were classified by symptom type as hypoperfusion, non-hypoperfusion, or indeterminate, and pretreatment asymptomatic intervals were noted. Hypoperfusion lesions and indeterminate or non-hypoperfusion lesions with ≥14 days of asymptomatic interval were classified as stable. Percentage stenosis was calculated and compared against these other symptom features for value in predicting technical complication, ischemic stroke, disability, or death at 90 days and 2 years using univariate and multivariate analysis. RESULTS: 130 lesions were treated in 124 patients. The only statistically significant percent stenosis finding was lesions with 60-99% stenosis were less likely to have technical complications. In univariate analysis, stroke at 2 years was less common with hypoperfusion and stable lesions. In multivariate analysis, only hypoperfusion status was associated with lower stroke rates at 2 years. CONCLUSIONS: Lesion stability features, particularly non-hypoperfusion symptomatology, outperform percentage stenosis in predicting outcomes following treatment of ICAD with stents. Further examination is needed to better classify the natural history of ICAD and more precisely classify lesion stability.

EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.

BACKGROUND: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. PATIENTS AND METHODS: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. RESULTS: Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. CONCLUSIONS: New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.

Recurrent osteosarcoma with a single pulmonary metastasis: a multi-institutional review.

BACKGROUND: Late relapse and solitary lesion are positive prognostic factors in recurrent osteosarcoma. METHODS: We reviewed the records of 39 patients treated at three major centres for recurrent osteosarcoma with a single pulmonary metastasis more than 1 year after diagnosis. We analysed their outcomes with respect to clinical factors and treatment with chemotherapy. RESULTS: Median age at diagnosis was 14.6 years. Relapse occurred at a median of 2.5 years (range, 1.2-8.2 years) after initial diagnosis. At relapse, all patients were treated by metastasectomy; 12 (31%) patients also received chemotherapy. There was no difference in time to recurrence or nodule size between the patients who received or did not receive chemotherapy at relapse. Sixteen patients had no subsequent recurrence, 13 of whom survive without evidence of disease. The 5-year and 10-year estimates of post-relapse event-free survival (PREFS) were 33.0±7.5% and 33.0±9.6%, respectively, and of post-relapse survival (PRS) 56.8±8.6% and 53.0±11.0%, respectively. There was a trend for nodules <1.5 cm to correlate positively with PREFS (P=0.070) but not PRS (P=0.49). Chemotherapy at first relapse was not associated with PREFS or PRS. CONCLUSION: Approximately half of the patients with recurrent osteosarcoma presenting as a single pulmonary metastasis more than 1 year after diagnosis were long-term survivors. Metastasectomy was the primary treatment; chemotherapy did not add benefit.

Symptom differences and pretreatment asymptomatic interval affect outcomes of stenting for intracranial atherosclerotic disease.

BACKGROUND AND PURPOSE: Different types of symptomatic intracranial stenosis may respond differently to interventional therapy. We investigated symptomatic and pathophysiologic factors that may influence clinical outcomes of patients with intracranial atherosclerotic disease who were treated with stents. MATERIALS AND METHODS: A retrospective analysis was performed of patients treated with stents for intracranial atherosclerosis at 4 centers. Patient demographics and comorbidities, lesion features, treatment features, and preprocedural and postprocedural functional status were noted. χ(2) univariate and multivariate logistic regression analysis was performed to assess technical results and clinical outcomes. RESULTS: One hundred forty-two lesions in 131 patients were analyzed. Lesions causing hypoperfusion ischemic symptoms were associated with fewer strokes by last contact [χ(2) (1, n = 63) = 5.41, P = .019]. Nonhypoperfusion lesions causing symptoms during the 14 days before treatment had more strokes by last contact [χ(2) (1, n = 136), 4.21, P = .047]. Patients treated with stents designed for intracranial deployment were more likely to have had a stroke by last contact (OR, 4.63; P = .032), and patients treated with percutaneous balloon angioplasty in addition to deployment of a self-expanding stent were less likely to be stroke free at point of last contact (OR, 0.60; P = .034). CONCLUSIONS: More favorable outcomes may occur after stent placement for lesions causing hypoperfusion symptoms and when delaying stent placement 7-14 days after most recent symptoms for lesions suspected to cause embolic disease or perforator ischemia. Angioplasty performed in addition to self-expanding stent deployment may lead to worse outcomes, as may use of self-expanding stents rather than balloon-mounted stents.

Mifamurtide in metastatic and recurrent osteosarcoma: a patient access study with pharmacokinetic, pharmacodynamic, and safety assessments.

PURPOSE: This non-randomized, patient-access protocol, assessed both safety and efficacy outcomes following liposomal muramyl-tripeptide-phosphatidylethanolamine (L-MTP-PE; mifamurtide) in patients with high-risk, recurrent and/or metastatic osteosarcoma. METHODS: Patients received mifamurtide 2 mg/m(2) intravenously twice-weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration-time profiles were collected. Adverse events within 24 hours of drug administration were classified as infusion-related adverse events (IRAE); other AEs and overall survival (OS) were assessed. RESULTS: The study began therapy in January 2008; the last patient completed therapy in October 2012. Two hundred five patients were enrolled; median age was 16.0 years and 146/205 (71%) had active disease. Mifamurtide serum concentrations declined rapidly in the first 30 minutes post-infusion, then in a log-linear manner 2-6 hours post-dose; t1/2 was 2 hours. There were no readily apparent relationships between age and BSA-normalized clearance, half-life, or pharmacodynamic effects, supporting the dose of 2 mg/m(2) mifamurtide across the age range. Patients reported 3,679 IRAE after 7,482 mifamurtide infusions. These were very rarely grade 3 or 4 and most commonly included chills + fever or headache + fatigue symptom clusters. One- and 2-year OS was 71.7% and 45.9%. Patients with initial metastatic disease or progression approximated by within 9 months of diagnosis (N = 40) had similar 2-year OS (39.9%) as the entire cohort (45.9%) CONCLUSIONS: Mifamurtide had a manageable safety profile; PK/PD of mifamurtide in this patient access study was consistent with prior studies. Two-year OS was 45.9%. A randomized clinical trial would be required to definitively determine impact on patient outcomes.

Endovascular therapy of acute ischemic stroke: report of the Standards of Practice Committee of the Society of NeuroInterventional Surgery.

OBJECTIVE: To summarize and classify the evidence for the use of endovascular techniques in the treatment of patients with acute ischemic stroke. METHODS: Recommendations previously published by the American Heart Association (AHA) (Guidelines for the early management of adults with ischemic stroke (Circulation 2007) and Scientific statement indications for the performance of intracranial endovascular neurointerventional procedures (Circulation 2009)) were vetted and used as a foundation for the current process. Building on this foundation, a critical review of the literature was performed to evaluate evidence supporting the endovascular treatment of acute ischemic stroke. The assessment was based on guidelines for evidence based medicine proposed by the Stroke Council of the AHA and the University of Oxford, Centre for Evidence Based Medicine (CEBM). Procedural safety, technical efficacy and impact on patient outcomes were specifically examined.

Society of NeuroInterventional Surgery Standards of Practice: general considerations.

This is the first in a set of documents intended to standardize techniques, procedures, and practices in the field of endovascular surgical neuroradiology. Standards are meant to define core practices for peer review, comparison, and improvement. Standards and guidelines also form the basic dialogue, reporting, and recommendations for ongoing practices and future development.

Evaluation of the antibiotic biosynthetic potential of the genus Amycolatopsis and description of Amycolatopsis circi sp. nov., Amycolatopsis equina sp. nov. and Amycolatopsis hippodromi sp. nov.

AIMS: To describe three new Amycolatopsis strains and assess the antibiotic biosynthetic potential of the genus. METHODS AND RESULTS: Three strains, designated S1·3(T) , S3·6(T) and SE(8)3(T) , belonging to the genus Amycolatopsis were isolated and found to cluster together by 16S rRNA and gyrB gene-based phylogenetic analysis. Genetic distance values, based on the gyrB gene, were calculated between the strains and their closest relatives and were all above the threshold value of 0·02 that has been proposed to distinguish Amycolatopsis type strains. DNA-DNA hybridization experiments against related type strains confirmed that strain S3·6(T) represents a unique genomic species. Strain S3·6(T) was also found to be distinct from strains S1·3(T) and SE(8)3(T) , the latter two of which were also shown to be distinct from each other. Antibiotic biosynthetic genes were identified from multiple Amycolatopsis strains, and their presence was found to be phylogenetically associated. CONCLUSIONS: The data presented in this study indicate that strains S1·3(T) , SE(8)3(T) and S3·6(T) belong to three novel species, for which the names Amycolatopsis circi sp. nov. (= DSM 45561(T) = NRRL B-24841(T) ), Amycolatopsis equina sp. nov. (= DSM 45563(T) = NRRL B-24842(T) ) and Amycolatopsis hippodromi sp. nov. (= DSM 45562(T) = NRRL B-24843(T) ) are proposed. SIGNIFICANCE AND IMPACT OF THE STUDY: Three new species of Amycolatopsis are described, and the knowledge of the antibiotic biosynthetic potential of the genus has been extended.

Observer agreement regarding the necessity of retreatment of previously coiled recurrent cerebral aneurysms.

BACKGROUND AND PURPOSE: The decision regarding whether or not to retreat a previously treated aneurysm not only directly impacts patient care but also serves as a primary outcome measure in numerous, leading randomized controlled trials of modified coils. Our aim was to determine the degree of interobserver variability regarding the need and type of treatment for recurrent aneurysms following coil embolization. MATERIALS AND METHODS: Twenty-seven previously treated recurrent aneurysms were identified. Five independent readers rated each aneurysm on a 5-point scale: 1, definitely do not retreat; 2, probably do not retreat; 3, unsure; 4, probably retreat; and 5, definitely retreat. The readers noted, in grades 2-5, the type of retreatment preferred, including simple coiling, balloon- or stent-assist coiling, or surgical clipping. Intraobserver agreement κ was calculated. Retreatment recommendations were evaluated between observers by using a Wilcoxon signed rank comparison. Descriptive statistics were performed for categoric treatment-type comparisons. RESULTS: At least 2- or 3-point differences between 2 readers were present in 17 (63%) and 11 (41%) of 27 cases, respectively. The median κ was 0.27 (range, 0.04-0.43), which indicates fair agreement. Differences between readers varied, with readers 4 and 5 more often recommending retreatment compared with reviewers 1-3 (P < .05). Wide variation was noted in treatment approach, with recommendations for surgical clipping ranging from 2 (7%) to 18 (67%) of 27 cases between readers 1 and 5. CONCLUSIONS: The current study demonstrates substantial variability among observers not only in whether to retreat a recurrent aneurysm but also how to treat it. These findings suggest that patient management varies widely across treating physicians and also calls into question the use of "retreatment" as an objective end point in clinical trials.

Performance and training standards for endovascular ischemic stroke treatment.

Stroke is the third leading cause of death in the USA, Canada, Europe, and Japan. According to the American Heart Association and the American Stroke Association, there are now 750,000 new strokes that occur each year, resulting in 200,000 deaths, or 1 of every 16 deaths, per year in the USA alone. Endovascular therapy for patients with acute ischemic stroke is an area of intense investigation. The American Stroke Association has given a qualified endorsement of intra-arterial thrombolysis in selected patients. Intra-arterial thrombolysis has been studied in two randomized trials and numerous case series. Although two devices have been granted FDA approval with an indication for mechanical stroke thrombectomy, none of these thrombectomy devices has demonstrated efficacy for the improvement of patient outcomes. The purpose of the present document is to define what constitutes adequate training to perform neuroendovascular procedures in patients with acute ischemic stroke and what performance standards should be adopted to assess outcomes. These guidelines have been written and approved by multiple neuroscience societies which historically have been directly involved in the medical, surgical and endovascular care of patients with acute stroke. The participating member organizations of the Neurovascular Coalition involved in the writing and endorsement of this document are the Society of NeuroInterventional Surgery, the American Academy of Neurology, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Cerebrovascular Section, and the Society of Vascular & Interventional Neurology.

Reporting standards for endovascular repair of saccular intracranial cerebral aneurysms.

BACKGROUND AND PURPOSE: The goal of this article is to provide consensus recommendations for reporting standards, terminology, and written definitions when reporting on the radiological evaluation and endovascular treatment of intracranial, cerebral aneurysms. These criteria can be used to design clinical trials, to provide uniformity of definitions for appropriate selection and stratification of patients, and to allow analysis and meta-analysis of reported data. METHODS: This article was written under the auspices of the Joint Writing Group of the Technology Assessment Committee, Society of NeuroInterventional Surgery, Society of Interventional Radiology; Joint Section on Cerebrovascular Neurosurgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons; and Section of Stroke and Interventional Neurology of the American Academy of Neurology. A computerized search of the National Library of Medicine database of literature (PubMed) from January 1991 to December 2007 was conducted with the goal to identify published endovascular cerebrovascular interventional data about the assessment and endovascular treatment of cerebral aneurysms useful as benchmarks for quality assessment. We sought to identify those risk adjustment variables that affect the likelihood of success and complications. This article offers the rationale for different clinical and technical considerations that may be important during the design of clinical trials for endovascular treatment of cerebral aneurysms. Included in this guidance article are suggestions for uniform reporting standards for such trials. These definitions and standards are primarily intended for research purposes; however, they should also be helpful in clinical practice and applicable to all publications. CONCLUSIONS: The evaluation and treatment of brain aneurysms often involve multiple medical specialties. Recent reviews by the American Heart Association have surveyed the medical literature to develop guidelines for the clinical management of ruptured and unruptured cerebral aneurysms. Despite efforts to synthesize existing knowledge on cerebral aneurysm evaluation and treatment, significant inconsistencies remain in nomenclature and definition for research and reporting purposes. These operational definitions were selected by consensus of a multidisciplinary writing group to provide consistency for reporting on imaging in clinical trials and observational studies involving cerebral aneurysms. These definitions should help different groups to publish results that are directly comparable.

Patient radiation exposure during diagnostic and therapeutic interventional neuroradiology procedures.

PURPOSE: Increasing in number and complexity, interventional neuroradiology (INR) procedures are becoming an important source of radiation exposure for patients. In accordance with the ALARA principle, radiation exposure during INR procedures should be curtailed as much as possible while reaching successful treatment outcomes. Moreover, the extent of radiation exposure should be one outcome measure used to assess new technologies and procedural efficacy, and training programs should include techniques for exposure limitation. This study provides a methodology and preliminary data to assess radiation exposure during different INR procedure types. MATERIALS AND METHODS: All patients undergoing endovascular procedures in two biplanar dedicated neuroangiography suites at a major academic medical center were monitored according to procedure type, pathological indication, fluoroscopy time and machine-generated patient dose estimates between April 2006 and July 2008. RESULTS: 1678 patients underwent cerebral arteriography during the study period. Women (62.1%) accounted for the majority of patients, but men (38.9%) were more likely to undergo an interventional procedure than women (32.8%). Diagnostic studies accounted for 64.9% of procedures. Variable exposures were found between diagnostic and interventional procedures. Exposure differed depending on indications for the procedure and procedure type. CONCLUSION: Radiation exposure is an increasingly important consideration in the development of minimally invasive neurological procedures including cerebral angiography and INR. The type of procedure and lesion type allow the practitioner to estimate radiation exposure. Such information informs the clinical decision making process. Normative data should be collected and used for comparison purposes as one measure of technical and procedural success.

Search for muon neutrino and antineutrino disappearance in MiniBooNE.

The MiniBooNE Collaboration reports a search for nu_{micro} and nu[over]_{micro} disappearance in the Deltam;{2} region of 0.5-40 eV;{2}. These measurements are important for constraining models with extra types of neutrinos, extra dimensions, and CPT violation. Fits to the shape of the nu_{micro} and nu[over]_{micro} energy spectra reveal no evidence for disappearance at the 90% confidence level (C.L.) in either mode. The test of nu[over]_{micro} disappearance probes a region below Deltam;{2} = 40 eV;{2} never explored before.

Measurement of the ratio of the numu charged-current single-pion production to quasielastic scattering with a 0.8 GeV neutrino beam on mineral oil.

Using high statistics samples of charged-current numu interactions, the MiniBooNE [corrected] Collaboration reports a measurement of the single-charged-pion production to quasielastic cross section ratio on mineral oil (CH2), both with and without corrections for hadron reinteractions in the target nucleus. The result is provided as a function of neutrino energy in the range 0.4 GeV

Measurement of numicro and nue events in an off-axis horn-focused neutrino beam.

We report the first observation of off-axis neutrino interactions in the MiniBooNE detector from the NuMI beam line at Fermilab. The MiniBooNE detector is located 745 m from the NuMI production target, at 110 mrad angle (6.3 degrees) with respect to the NuMI beam axis. Samples of charged-current quasielastic numicro and nue interactions are analyzed and found to be in agreement with expectation. This provides a direct verification of the expected pion and kaon contributions to the neutrino flux and validates the modeling of the NuMI off-axis beam.

Unexplained excess of electronlike events from a 1-GeV neutrino beam.

The MiniBooNE Collaboration observes unexplained electronlike events in the reconstructed neutrino energy range from 200 to 475 MeV. With 6.46x10;{20} protons on target, 544 electronlike events are observed in this energy range, compared to an expectation of 415.2+/-43.4 events, corresponding to an excess of 128.8+/-20.4+/-38.3 events. The shape of the excess in several kinematic variables is consistent with being due to either nu_{e} and nu[over ]_{e} charged-current scattering or nu_{mu} neutral-current scattering with a photon in the final state. No significant excess of events is observed in the reconstructed neutrino energy range from 475 to 1250 MeV, where 408 events are observed compared to an expectation of 385.9+/-35.7 events.

Performance and training standards for endovascular ischemic stroke treatment.

Stroke is the third leading cause of death in the USA, Canada, Europe, and Japan. According to the American Heart Association and the American Stroke Association, there are now 750,000 new strokes that occur each year, resulting in 200,000 deaths, or 1 of every 16 deaths, per year in the USA alone. Endovascular therapy for patients with acute ischemic stroke is an area of intense investigation. The American Stroke Association has given a qualified endorsement of intra-arterial thrombolysis in selected patients. Intra-arterial thrombolysis has been studied in two randomized trials and numerous case series. Although two devices have been granted FDA approval with an indication for mechanical stroke thrombectomy, none of these thrombectomy devices has demonstrated efficacy for the improvement of patient outcomes. The purpose of the present document is to define what constitutes adequate training to perform neuroendovascular procedures in patients with acute ischemic stroke and what performance standards should be adopted to assess outcomes. These guidelines have been written and approved by multiple neuroscience societies which historically have been directly involved in the medical, surgical and endovascular care of patients with acute stroke. The participating member organizations of the Neurovascular Coalition involved in the writing and endorsement of this document are the Society of NeuroInterventional Surgery, the American Academy of Neurology, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Cerebrovascular Section, and the Society of Vascular & Interventional Neurology.