Review of skin dose calculation software in interventional cardiology

PurposeIn interventional cardiology, patients may be exposed to high doses to the skin resulting in skin burns following single or multiple procedures. Reviewing and analysing available software (online or offline) may help medical physicists assessing the maximum skin dose to the patient together with the dose distribution during (or after) these procedures.Method and resultsCapabilities and accuracy of available software were analysed through an extensive bibliography search and contacts with both vendor and authors. Their markedly differed among developers.In total, 22 software were identified and reviewed according to their algorithms and their capabilities. Special attention was dedicated to their main features and limitations of interest for the intended clinical use.While the accuracy of the 12 software products validated with measurements on phantoms was acceptable (within ± 25%), the agreement was poor for the two products validated on patients (within ± 43% and ± 76%, respectively). In addition, no software has been validated on angiographic units from all manufacturers, though several software developers claimed vendor-independent transportability. Only one software allows for multiple procedures dose calculation.ConclusionLarge differences among vendors made it clear that work remains to be done before an accurate and reliable skin dose mapping is available for all patients.     

Cellular therapy in cardiology

Cardiac cell therapy has been initially designed to regenerate the infarcted myocardium through its repopulation by new cells able to restore function of scar areas. Six years after the first human application of this novel approach, it is timely appropriate to review the results of the first randomised trials in the three major indications, i.e., acute myocardial infarction, heart failure, and refractory angina. It should be recognized that the results are mixed, with benefits ranging from absent to transient and, at most, marginal. However, lessons drawn from this first wave of clinical series and the experimental data that have been concomitantly collected are multiple and highly informative. They indicate that adult stem cells, whether muscular or bone marrow-derived, fail to generate new cardiomyocytes. They suggest that the potential benefits of cardiac cell therapy are thus mediated by alternate mechanisms such as limitation of left ventricular remodelling or paracrine activation of signalling pathways involved in angiogenesis. They highlight the fact that the therapeutic benefits of grafted cells will not be fully exploited until issues of cell transfer and postengraftment survival have not been adequately addressed. These observations thus allow us to better fine-tune upcoming research, which should specifically concentrate on the development of cells featuring a true regeneration potential. In this setting, the greatest promises are currently held by embryonic stem cells.     

Establishing the European diagnostic reference levels for interventional cardiology

Interventional cardiac procedures may be associated with high patient doses and therefore require special attention to protect the patients from radiation injuries such as skin erythema, cardiovascular tissue reactions or radiation-induced cancer. In this study, patient exposure data is collected from 13 countries (37 clinics and nearly 50 interventional rooms) and for 10 different procedures. Dose data was collected from a total of 14,922 interventional cardiology procedures. Based on these data European diagnostic reference levels (DRL) for air kerma-area product are suggested for coronary angiography (CA, DRL = 35 Gy cm²), percutaneous coronary intervention (PCI, 85 Gy cm²), transcatheter aortic valve implantation (TAVI, 130 Gy cm²), electrophysiological procedures (12 Gy cm²) and pacemaker implantations. Pacemaker implantations were further divided into single-chamber (2.5 Gy cm²) and dual chamber (3.5 Gy cm²) procedures and implantations of cardiac resynchronization therapy pacemaker (18 Gy cm²). Results show that relatively new techniques such as TAVI and treatment of chronic total occlusion (CTO) often produce relatively high doses, and thus emphasises the need for use of an optimization tool such as DRL to assist in reducing patient exposure. The generic DRL presented here facilitate comparison of patient exposure in interventional cardiology.     

Assessment of eye doses to staff involved in interventional cardiology procedures in Kuwait

In this study, which is the first of its kind in the gulf region, eye doses of interventional cardiologists and nurses were measured using active dosimeters for left and right eyes, in 60 percutaneous coronary interventions in three main hospitals in Kuwait. The dose given in terms of H_p(0.07) per procedure when ceiling suspended screens were used by main operators ranged from 18.5 to 30.3 µSv for the left eye and from 12.6 to 23.6 µSv for the right eye. Taking into account typical staff workload, the results show that the dose limit of 20 mSv/year to the eyes can be exceeded for interventional cardiologists in some situations, which demonstrates the need of using additional effective radiation protection tools, e.g. protective eye spectacles, in addition to the regular and proper use of ceiling suspended screens. With indications of increase in workload, the need for availability of a dedicated active dosimeter for the regular monitoring of eye doses is emphasized.

     

Updating national diagnostic reference levels for interventional cardiology and methodological aspects

The aim of this study is to propose national diagnostic reference levels (DRL) for updating in the field of interventional cardiology and to include technical details to help plan optimization.Medical physics experts and interventional cardiologists from 14 hospitals provided patient dose indicators from coronary angiography and percutaneous coronary interventions. Information about X-ray system dose settings and image quality was also provided.The dose values from 30,024 procedures and 26 interventional laboratories were recorded. The national DRLs proposed for coronary angiography and percutaneous coronary interventions were respectively 39 and 78 Gy·cm² for air kerma area product (P_KA), 530 and 1300 mGy for air kerma at reference point (K_a,r), 6.7 and 15 min of fluoroscopy time and 760 and 1300 cine images. 36% of the KAP meters required correction factors from 10 to 35%. The dose management systems should allow these corrections to be included automatically. The dose per image in cine in reference conditions differed in a factor of 5.5.Including X-ray system dose settings in the methodology provides an insight into the differences between hospitals. The DRLs proposed for Spain in this work were similar to those proposed in the last European survey. The poor correlation between X-ray systems dose settings and patient dose indicators highlights that other factors such as operation protocols and complexity may have more impact in patient dose indicators, which allows a wide margin for optimization. Dose reduction technology together with appropriate training programs will be determinant in the future reduction of patient dose indicators.     

The future direction of cholesterol-lowering therapy

PURPOSE OF REVIEW: Observational studies suggest a continuous positive relationship between vascular risk and cholesterol without any lower threshold level. We review recent and future clinical trials addressing the question of optimal treatment goals for cholesterol reduction and how these relate to present guidelines. With increasing focus on greater cholesterol reduction, new approaches to lipid-lowering therapy are being developed; we discuss some of these agents including the new statin, rosuvastatin and novel cholesterol transport inhibitors such as ezetimibe. RECENT FINDINGS: The Heart Protection Study demonstrated that LDL cholesterol reduction to levels as low as 1.7 mmol/l was associated with significant clinical benefit in a wide range of high-risk individuals, irrespective of baseline cholesterol levels, with no apparent threshold level for LDL cholesterol with respect to cardiovascular risk. The Heart Protection Study also demonstrated that the benefits of LDL cholesterol reduction extend into peripheral vascular disease and cerebrovascular disease prevention and suggest that the most recent National Cholesterol Education Program Adult Treatment Panel III guidelines, with LDL cholesterol targets of 2.6 mmol/l, may result in undertreatment of a large number of patients. Various large end-point trials, including Treating to New Targets and Study of Effectiveness of Additional Reductions in Cholesterol and Homocysteine will attempt to further address the issue of optimal LDL cholesterol reduction. New therapies are being developed to meet the challenge of more intensive cholesterol lowering. Rosuvastatin is a potent, hydrophilic enantiomeric statin producing reductions in LDL cholesterol of 40-69% over its dose range of 5-80 mg. Ezetimibe is a selective cholesterol absorption inhibitor, with a site of action at the intestinal epithelium. Optimum reductions in LDL cholesterol of up to 25 and 60% reduction in chylomicron cholesterol content are seen with a 10-mg dose. SUMMARY: Evidence is accumulating supporting the safety and benefits of aggressive cholesterol reduction, with no apparent threshold for LDL cholesterol. New therapies will aid in achieving lower cholesterol levels and the use of combination therapies targeting different aspects of cholesterol metabolism may produce additional benefits. Outcome studies are awaited to further address these issues.     

The future of human gene therapy

Human gene therapy (HGT) is defined as the transfer of nucleic acids (DNA) to somatic cells of a patient which results in a therapeutic effect, by either correcting genetic defects or by overexpressing proteins that are therapeutically useful. In the past, both the professional and the lay community had high (sometimes unreasonably high) expectations from HGT because of the early promise of treating or preventing diseases effectively and safely by this new technology. Although the theoretical advantages of HGT are undisputable, so far HGT has not delivered the promised results: convincing clinical efficacy could not be demonstrated yet in most of the trials conducted so far, while safety concerns were raised recently as the consequence of the "Gelsinger Case" in Philadelphia. This situation resulted from the by now well-recognized disparity between theory and practice. In other words, the existing technologies could not meet the practical needs of clinically successful HGT so far. However, over the past years, significant progress was made in various enabling technologies, in the molecular understanding of diseases and the manufacturing of vectors. HGT is a complex process, involving multiple steps in the human body (delivery to organs, tissue targeting, cellular trafficking, regulation of gene expression level and duration, biological activity of therapeutic protein, safety of the vector and gene product, to name just a few) most of which are not completely understood. The prerequisite of successful HGT include therapeutically suitable genes (with a proven role in pathophysiology of the disease), appropriate gene delivery systems (e.g., viral and non-viral vectors), proof of principle of efficacy and safety in appropriate preclinical models and suitable manufacturing and analytical processes to provide well-defined HGT products for clinical investigations. The most promising areas for gene therapy today are hemophilias, for monogenic diseases, and cardiovascular diseases (more specifically, therapeutic angiogenesis for myocardial ischemia and peripheral vascular disease, restenosis, stent stenosis and bypass graft failure) among multigenic diseases. This is based on the relative ease of access of blood vessels for HGT, and also because existing gene delivery technologies may be sufficient to achieve effective and safe therapeutic benefits for some of these indications (transient gene expression in some but not all affected cells is required to achieve a therapeutic effect at relatively low [safe] dose of vectors). For other diseases (including cancer) further developments in gene delivery vectors and gene expression systems will be required. It is important to note, that there will not be a "universal vector" and each clinical indication may require a specific set of technical hurdles to overcome. These will include modification of viral vectors (to reduce immunogenicity, change tropism and increase cloning capacity), engineering of non-viral vectors by mimicking the beneficial properties of viruses, cell-based gene delivery technologies, and development of innovative gene expression regulation systems. The technical advances together with the ever increasing knowledge and experience in the field will undoubtedly lead to the realization of the full potential of HGT in the future.     

The future of gene therapy in the UK

Gene therapy encompasses a spectrum of therapeutic strategies, ranging from the compelling concept of using wild type copies of genes to correct the root cause of recessive genetic disorders through to using genes to mediate powerful and selective toxicity to cancer cells. Inspirational for the general public as well as the bioscience community, gene therapy has been grabbing the headlines--for good and bad reasons--regularly for the past 15 years. In this personal appraisal, Professor Len Seymour assesses the progress of gene therapy in the UK and what it might deliver in the foreseeable future.