Access to beds for interventional radiology patients: improving patient care.

This review describes the rationale in support of admitting rights for interventional radiologists and presents options for the management of interventional radiology (IR) inpatients. The manuscript also discusses wider aspects of IR involvement in inpatient treatment, such as income and funding for IR services, and the implications for IR as a clinical specialty.

Developing day-case units: imperative for optimal patient care in interventional radiology.

As interventional radiology (IR) treatments have evolved, they have become less invasive, enabling rapid recovery, which expedites ambulation and promotes same-day discharge. As a result of this, a significant proportion of IR elective work can be provided using a day-case service model. Reconfiguration of IR services to increase day-case procedures using a dedicated IR day-case unit (RDU) to facilitate the passage of patients is vital to ensure best medical practice. The aim of this review is to discuss the benefits of day-case IR procedures, the optimal structure of an RDU, and to inform radiologists how to introduce and/or improve day-case IR services in their IR practice.

Inhibition of TGF-ß signaling in genetically engineered tumor antigen-reactive T cells significantly enhances tumor treatment efficacy.

Transforming growth factor ß (TGF-ß) is a cytokine with complex biological functions that may involve tumor promotion or tumor suppression. It has been reported that multiple types of tumors secrete TGF-ß, which can inhibit tumor-specific cellular immunity and may represent a major obstacle to the success of tumor immunotherapy. In this study, we sought to enhance tumor immunotherapy using genetically modified antigen-specific T cells by interfering with TGF-ß signaling. We constructed three γ-retroviral vectors, one that expressed TGF-ß-dominant-negative receptor II (DNRII) or two that secreted soluble TGF-ß receptors: soluble TGF-ß receptor II (sRII) and the sRII fused with mouse IgG Fc domain (sRIIFc). We demonstrated that T cells genetically modified with these viral vectors were resistant to exogenous TGF-ß-induced smad-2 phosphorylation in vitro. The functionality of antigen-specific T cells engineered to resist TGF-ß signaling was further evaluated in vivo using the B16 melanoma tumor model. Antigen-specific CD8+ T cells (pmel-1) or CD4+ T cells (tyrosinase-related protein-1) expressing DNRII dramatically improved tumor treatment efficacy. There was no enhancement in the B16 tumor treatment using cells secreting soluble receptors. Our data support the potential application of the blockade of TGF-ß signaling in tumor-specific T cells for cancer immunotherapy.

Technical considerations of endovascular management of true visceral artery aneurysms.

BACKGROUND: True visceral artery aneurysms are potentially complex to treat but with advances in technology and increasing interventional radiology expertise over the past decade are now increasingly the domain of the interventional radiologist. BODY: The interventional approach is based on localization of the aneurysm and identification of the anatomical determinants to treat these lesions to prevent aneurysm rupture. Several different endovascular techniques are available and should be selected carefully, dependent on the aneurysm morphology. Standard endovascular treatment options include stent-graft placement and trans-arterial embolisation. Different strategies are divided into parent artery preservation and parent artery sacrifice techniques. Endovascular device innovations now include multilayer flow-diverting stents, double-layer micromesh stents, double-lumen balloons and microvascular plugs and are also associated with high rates of technical success. CONCLUSION: Complex techniques such as stent-assisted coiling and balloon-remodeling techniques are useful techniques and require advanced embolisation skills and are further described.

Operator-controlled imaging significantly reduces radiation exposure during EVAR.

INTRODUCTION: Adoption of endovascular aneurysm repair (EVAR) has led to significant reductions in the short-term morbidity and mortality associated with abdominal aortic aneurysm (AAA) repair. However, EVAR may expose both patient and interventionalist to potentially harmful levels of radiation, particularly as more complex procedures are undertaken. The aim of this study was to assess whether changing from radiographer-controlled imaging to a system of operator-controlled imaging (OCI) would influence radiation exposure, screening time or contrast dose during EVAR. METHOD: Retrospective analysis identified patients that had undergone elective EVAR for infra-renal AAA before or after the change to operator-controlled imaging. Data were collected for radiation dose (measured as dose area product; DAP), screening time, total delivered contrast volume and operative duration. Data were also collected for maximum aneurysm diameter, patient age, gender and body mass index. RESULTS: 122 patients underwent EVAR for infra-renal AAA at a single centre between January 2011 and December 2011. 57 of these were prior to installation of OCI and 65 after installation. Median DAP was significantly lower after installation of OCI (4.9 mGy m(2); range 1.25-13.3) than it had been before installation (6.9 mGy m(2); range 1.91-95.0) (p = 0.005). Median screening times before and after installation of OCI were 20.0 min and 16.2 min respectively (p = 0.027) and median contrast volumes before and after the change to OCI were 100 ml and 90 ml respectively (p = 0.21). CONCLUSION: Introduction of operator-controlled imaging can significantly reduce radiation exposure during EVAR, with particular reduction in the number of 'higher-dose' cases.

Reduction in SIV replication in rhesus macaques infused with autologous lymphocytes engineered with antiviral genes.

Simian immunodeficiency virus (SIV) infection of nonhuman primates is one of the most relevant animals models of HIV infection in humans. To test a potential anti-HIV gene therapy strategy in this model, CD4-enriched lymphocytes from three rhesus macaques were subjected to retrovirally mediated gene transfer with a vector expressing an antisense tat/rev gene. This group of animals and three control macaques were subsequently infected with SIVmac239. Blood and lymph nodes from all macaques were sampled for more than a year to monitor the progress of infection. Although all animals became infected, the animals that received the lymphocytes engineered with the antisense vector demonstrated a significant reduction in viral load in both peripheral blood and lymph nodes, had sustained numbers of CD4+ cells, and exhibited little disruption of lymph node architecture.

Efficient nonviral Sleeping Beauty transposon-based TCR gene transfer to peripheral blood lymphocytes confers antigen-specific antitumor reactivity.

Genetically engineered lymphocytes hold promise for the treatment of genetic disease, viral infections and cancer. However, current methods for genetic transduction of peripheral blood lymphocytes rely on viral vectors, which are hindered by production and safety-related problems. In this study, we demonstrated an efficient novel nonviral platform for gene transfer to lymphocytes. The Sleeping Beauty transposon-mediated approach allowed for long-term stable expression of transgenes at approximately 50% efficiency. Utilizing transposon constructs expressing tumor antigen-specific T-cell receptor genes targeting p53 and MART-1, we demonstrated sustained expression and functional reactivity of transposon-engineered lymphocytes on encountering target antigen presented on tumor cells. We found that transposon- and retroviral-modified lymphocytes had comparable transgene expression and phenotypic function. These results demonstrate the promise of nonviral ex vivo genetic modification of autologous lymphocytes for the treatment of cancer and immunologic disease.

T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years.

In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.

Adipose tissue dysfunction in obese horses with equine metabolic syndrome.

BACKGROUND: Obesity is a common feature of equine metabolic syndrome (EMS). In other species, obese adipose tissue shows pathological features such as adipocyte hypertrophy, fibrosis, inflammation and impaired insulin signalling all of which contribute to whole body insulin dysregulation. Such adipose tissue dysfunction has not been investigated in horses. OBJECTIVES: To determine if obese horses with EMS have adipose tissue dysfunction characterised by adipocyte hypertrophy, fibrosis, inflammation and altered insulin signalling. STUDY DESIGN: Cross-sectional post-mortem study. METHODS: Samples of peri-renal (visceral) and retroperitoneal adipose tissue were obtained at post-mortem from healthy horses (n = 9) and horses with EMS (n = 6). Samples were analysed to determine average adipocyte size, fibrotic content and expression of inflammatory and insulin signalling genes. RESULTS: Horses with metabolic syndrome showed marked adipocyte hypertrophy and increased expression of adipokines (leptin) and inflammatory cytokines (TNFα, IL1ß and CCL2) in both adipose tissue depots compared to healthy horses. There were no differences in fibrosis or expression of genes relating to insulin signalling between the groups. MAIN LIMITATIONS: Cases used in this study had advanced EMS and may represent the end stage of the condition; the design of the study is such that we were unable to relate the identified adipose tissue dysfunction to whole body insulin dysregulation. CONCLUSIONS: Horses with obesity and EMS have significant dysfunction of the peri-renal and retroperitoneal adipose tissue that may contribute to whole body insulin dysregulation.

Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition.

In human gene therapy applications, lentiviral vectors may have advantages over gamma-retroviral vectors in several areas, including the ability to transduce nondividing cells, resistance to gene silencing and a potentially safer integration site profile. However, unlike gamma-retroviral vectors it has been problematic to drive the expression of multiple genes efficiently and coordinately with approaches such as internal ribosome entry sites or dual promoters. Using different 2A peptides, lentiviral vectors expressing two-gene T-cell receptors directed against the melanoma differentiation antigens gp100 and MART-1 were constructed. We demonstrated that addition of amino-acid spacer sequences (GSG or SGSG) before the 2A sequence is a prerequisite for efficient synthesis of biologically active T-cell receptors and that addition of a furin cleavage site followed by a V5 peptide tag yielded optimal T-cell receptor gene expression. Furthermore, we determined that the furin cleavage site was recognized in lymphocytes and accounted for removal of residual 2A peptides at the post-translational level with an efficiency of 20-30%, which could not be increased by addition of multiple furin cleavage sites. The novel bicistronic lentiviral vector developed herein afforded robust anti-melanoma activities to engineered peripheral blood lymphocytes, including cytokine secretion, cell proliferation and lytic activity. Such optimal vectors may have immediate applications in cancer gene therapy.

Actinomyces species as a cause of abscesses in nine horses.

The characteristics, history, clinical signs, treatment and outcome of nine horses with abscesses caused by Actinomyces species were reviewed. dna sequencing was used to determine the species of one of the isolates. The horses were one to 11 years of age, and the abscesses were most commonly located in the submandibular and retropharyngeal regions. The bacterium was usually cultured as the sole isolate and the horses were most often affected in the autumn. Most of the abscesses were treated with antimicrobials and drainage, but some of them recurred. The horses with submandibular abscesses had residual scar tissue that in some cases did not resolve.

Correlation of undermethylation of intracisternal A-particle genes with expression in murine plasmacytomas but not in NIH/3T3 embryo fibroblasts.

We report here comparative studies of DNA methylation and expression of intracisternal A-particle (IAP) genes in murine plasmacytomas, TEPC-15 and MOPC-315, in NIH/3T3 embryo fibroblasts, and in normal liver from young adult BALB/c mice. In Southern blot analysis using methylation-sensitive restriction enzymes, we observed hypomethylation of 4.7- and 5.3-kilobase pair IAP proviruses, and partial undermethylation of other IAP DNA fragments in TEPC-15, MOPC-315, and 3T3 cells, while most of these DNA fragments were hypermethylated in liver. The extent of undermethylation at 12 different sites including the long terminal repeat sequence region and 5'-flanking sequence within one specific IAP gene was found to be similar between 3T3 cells and plasmacytomas. Little or no undermethylation of these sites was found in liver. Hypomethylation of IAP genes, however, is not correlated with their expression in 3T3 cells (as it is found for plasmacytomas), since 3T3 cells, like liver cells, have no detectable transcripts. We also observed hypomethylation of the kappa-light chain gene in 3T3 cells, suggesting that undermethylation may be a generalized phenomenon in these cells. The relationships between gene undermethylation and the control of gene expression in 3T3 cells is discussed.

Percutaneous interventions following endovascular aneurysm sac sealing: Endoleak embolization and limb-related adverse events.

The Nellix endovascular aneurysm sealing system is a novel alternative to conventional endovascular aneurysm repair for aortic aneurysm management using paired balloon-expandable endografts supported by polymer-filled endobags to achieve sealing and anatomic fixation. Part of the promise of endovascular aneurysm sealing is increased resistance to lateral and longitudinal forces and a potential for reduced rates of device-related failures, particularly endoleaks. Initial efficacy data on this device are encouraging, but our knowledge of its associated complications and their management is limited. Reported adverse events include Type I and II endoleaks, graft stenosis, and occlusion. The aim of this article was to review the early experience of endovascular aneurysm sealing, focusing on the incidence, significance, and management of device-related complications.

Secondary interventions after endovascular aneurysm sac sealing: endoleak embolization and limb-related interventions.

The Nellix endovascular aneurysm sealing system is a novel alternative to conventional endovascular aneurysm repair for aortic aneurysm management using paired balloon expandable endografts supported by polymer-filled endobags to achieve sealing and anatomic fixation. Part of the promise of endovascular aneurysm sealing is increased resistance to lateral and longitudinal forces and thus a potential for reduced rates of device-related failures, particularly endoleaks. Initial efficacy data on this device are encouraging, but our knowledge of its associated complications and their management is limited. Reported adverse events include Type 1 and 2 endoleaks, graft stenosis and occlusion. The aim of this article is to review the early experience of endovascular aneurysm sealing focusing on the incidence, significance, and management of device-related complications.

Treatment of equine metabolic syndrome: A clinical case series.

REASONS FOR PERFORMING STUDY: Treatment of equine metabolic syndrome (EMS) is essential to improve insulin sensitivity and reduce the risk of laminitis. Calorie restriction and increased exercise are the mainstays of treatment but there is potential for poor owner compliance. OBJECTIVES: To determine whether significant weight loss accompanied by improvements in measures of insulin sensitivity can be achieved in horses and ponies with EMS managed by their owners in their normal environment under veterinary guidance. STUDY DESIGN: Retrospective clinical case series. METHODS: Horses and ponies attending 2 university hospitals for investigation and treatment of suspected EMS were eligible for inclusion in the study. Animals underwent a clinical examination, basal and dynamic endocrine testing; those with pituitary pars intermedia dysfunction (PPID) were excluded. Owners were given individually tailored diet and exercise programmes to follow for between 3 and 6 months. After the treatment period, clinical examination and endocrine tests were repeated and results compared to the initial assessment. RESULTS: Nineteen animals were recruited to the study, 17 with a history of laminitis. All animals showed a reduction in body condition score (P<0.001) and 18/19 had a reduction in bodyweight (P<0.001) between assessments. There were significant (P<0.05) reductions in basal insulin, insulin at 45 min during a combined glucose insulin tolerance test (CGIT), time for blood glucose concentration to return to baseline during a CGIT and mean area under the glucose curve. CONCLUSIONS: A diet and exercise programme tailored to the needs of the individual animal and implemented by the owner results in weight loss accompanied by improvements in insulin sensitivity.

Transiliac Paraendograft Embolisation of Type 2 Endoleak: An Alternative Approach for Endoleak Management.

Selective transarterial catheterisation and translumbar sac puncture are well established techniques for the management of significant type 2 endoleaks. We report an additional technique for endovascular access to the endoleak sac through the space between the iliac endograft and artery wall.

Transcatheter Embolisation of Proximal Type 1 Endoleaks Following Endovascular Aneurysm Sealing (EVAS) Using the Nellix Device: Technique and Outcomes.

AIM: To evaluate the technical success and mid-term outcomes following transcatheter embolisation of type 1a endoleak after Nellix endovascular aneurysm sealing (EVAS). MATERIALS AND METHODS: Seven patients (5 men; mean age 83; range 79-90) underwent transcatheter embolisation between July 2013 and August 2014. The average time from EVAS to embolisation was 136 days (range 6-301) and from endoleak diagnosis to embolisation was 20 days (range 2-50). Embolisation was performed with coils and Onyx in six cases and Onyx only in one case. Technical success, imaging and clinical outcomes of embolisation were reviewed. Technical success was defined as elimination of the endoleak on completion angiography and first imaging follow-up. Clinical success was defined as unchanged or decreased aneurysm sac size on subsequent follow-up (average 8 months; range 103-471 days). RESULTS: All cases were technically successful. One patient required a second endovascular procedure following Onyx reflux into the Nellix endograft and another patient required surgical closure of a brachial puncture site. All patients are endoleak free with stable sac size on the latest available follow-up imaging. CONCLUSION: If a type 1 endoleak occurs after EVAS, embolisation using Onyx with or without coils is feasible and effective with high technical success and freedom from endoleak recurrence at mid-term follow-up.

Thoracic Endovascular Aortic Repair for the Treatment of Aortic Dissection: Post-operative Imaging, Complications and Secondary Interventions.

Thoracic endovascular aortic repair (TEVAR) has become an accepted alternative to surgery for the treatment of aortic dissection (AD). Lifelong surveillance is obligatory following TEVAR to monitor the aortic morphology and detect associated complications. This is particularly important in AD where coverage of the primary intimal tear is necessary in achieving thrombosis and regression of the false lumen. A variety of imaging techniques may be used in assessing the technical success, outcome and complications, which may necessitate re-intervention. Of these, computed tomography angiography offers a fast, accessible and sensitive imaging modality and is established as the default surveillance tool. The purpose of this article is to review the imaging modalities, post-procedural appearances including complications and re-intervention strategies following TEVAR for AD.

Embolisation of a proximal type I endoleak post-Nellix aortic aneurysm repair complicated by reflux of Onyx into the Nellix endograft limb.

We report the first case of intervention for a proximal type 1 endoleak following Nellix endovascular aneurysm sealing repair of an aortic aneurysm. This was complicated by migration of Onyx into one of the Nellix graft limbs causing significant stenosis. Subsequent placement of a covered stent to affix the Onyx between the stent and the wall of the Nellix endograft successfully restored stent patency.

Potent inhibition of human immunodeficiency virus type 1 replication by conditionally replicating human immunodeficiency virus-based lentiviral vectors expressing envelope antisense mRNA.

We describe an HIV-based lentiviral vector that expresses a 1-kb antisense mRNA directed against the HIV-1 mRNAs containing env sequences. The expression of antisense env mRNAs (envAS) does not inhibit the synthesis of p24 expressed from the HIV-1 helper plasmid used to package the vector, as this helper has a deletion in the env gene. This allows the production of high-titer VSV-G pseudotyped lentiviral particles. In challenge experiments using unselected populations of SupT1 cells transduced with this vector, a complete inhibition of HIV-1 replication was observed for long periods of in vitro culture, even at high HIV-1 infectious doses. The potent inhibition of HIV-1 replication by this vector correlated with a low occurrence of mobilization of the vector to previously untransduced cells. The infectivity of the wild-type HIV-1 that escapes inhibition was highly inhibited, suggesting that the vector is providing HIV-1 inhibition of replication not only due to its antisense effect but also by competing for encapsidation and mobilization to noninfected cells.