Use of cardiac radiation therapy as bridging therapy to CAR-T for relapsed pediatric B-cell acute lymphoblastic leukemia.

The use of radiotherapy as bridging therapy to chimeric antigen receptor T-cell therapy (CAR-T) in pre-B acute lymphoblastic leukemia (B-ALL) has been minimally explored. Here, we present a boy with B-ALL who relapsed after allogeneic bone marrow transplant with disseminated disease, including significant symptomatic cardiovascular and gastrointestinal (GI) involvement. The cardiac and GI leukemic infiltrates were successfully treated with bridging radiation therapy (BRT) prior to CAR-T infusion. Using this approach, he successfully tolerated CAR-T with no evidence of disease or sequelae on 3-month follow-up. This is the first reported case of safe and effective delivery of cardiac BRT in B-ALL.

Effect of Radiation on the Expression of CVD-related miRNAs, Inflammation and Endothelial Dysfunction of HUVECs.

BACKGROUND/AIM: Radiotherapy (RT) can lead to cardiovascular disease (CVD). Evidence suggests that radiation modulates miRNA levels. Our purpose was to assess the acute response to radiation-induced modulation of the expression of miRNA-146a, miRNA-155, miRNA-221, and miRNA-222, inflammatory response and endothelial dysfunction on endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to 2 Gy RT, and intracellular levels of selected miRNAs were measured by real-time polymerase chain reaction at 2 and 24 h. Cytokine and adhesion molecule release were also assessed. RESULTS: Results showed that 2 Gy significantly increased the expression of miRNA-221 and miRNA-222, and reduced the level of miRNA-155 after 2 h; whereas miRNA-146a and miRNA-155 were significantly overexpressed and miRNA-222 was significantly down-regulated at 24 h. Interleukin-8 and soluble vascular cell adhesion molecule 1 levels were not affected by the studied RT. CONCLUSION: RT at 2 Gy modulated expression of selected miRNAs by endothelial cells after 2 and 24 h, which might be related to CVD development in patients who receive RT.

Radiotherapeutic implications of the updated ICRP thresholds for tissue reactions related to cataracts and circulatory diseases.

Radiation therapy of cancer patients involves a trade-off between a sufficient tumour dose for a high probability of local control and dose to organs at risk that is low enough to lead to a clinically acceptable probability of toxicity. The International Commission on Radiological Protection (ICRP) reviewed epidemiological evidence and provided updated estimates of 'practical' threshold doses for tissue injury, as defined at the level of 1% incidence, in ICRP Publication 118. Particular attention was paid to cataracts and circulatory diseases. ICRP recommended nominal absorbed dose threshold for these outcomes as low as 0.5 Gy. Threshold doses for tissue reactions can be reached in some patients during radiation therapy. Modern treatment planning systems do not account for such low doses accurately, and doses to therapy patients from associated imaging procedures are not generally accounted for. While local control is paramount, the observations of ICRP Publication 118 suggest that radiation therapy plans and processes should be examined with particular care. The research needs are discussed in this paper.

Measures to reduce radiation in a modern cardiac catheterization laboratory.

BACKGROUND: X-ray use in the catheterization laboratory is guided by the principle of as low as reasonably achievable. In accordance with this principle, we reduced the default fluoroscopic frame rate from 10 to 7.5 frames/s and increased the emphasis on the use of low-dose acquisition starting January 1, 2013. We aimed to study the impact of these measures on the total air kerma during diagnostic catheterization (DC) and percutaneous interventions (PCI). METHODS AND RESULTS: Propensity matching based on age, sex, body surface area, total fluoroscopy time, and total acquisition time was used to select matched patients for 2012 and 2013, further stratified by DC or PCI. The total air kerma was subsequently compared between 2012 and 2013, separately for DC and PCI. Median total air kerma during DC in 2013 was 625 mGy, which was significantly lower than the corresponding values in 2012 (median, 798 mGy; P<0.001). Similarly, median total air kerma during PCI in 2013 was 1675 mGy, which was significantly less than corresponding values in 2012 (median 2463 mGy, P<0.001). On comparison of air kerma rates between corresponding projections in 2 years, we observed a significant reduction in fluoroscopy- and acquisition-based air kerma rates in 2013, after institution of radiation reduction measures in all projections. CONCLUSIONS: With reduction in the default fluoroscopic frame rate and a greater use of low-dose acquisition, there has been a marked reduction in the total air kerma and air kerma rates for DC and PCI.

Boron tracedrug design for neutron dynamic therapeutics for LDL.

We describe our solution for removal of the low-density lipoprotein (LDL) depot contained in proteins and lipids as a 'druggable' target for atherosclerotic cardiovascular diseases by neutron dynamic therapy (NDT), which we developed using boron tracedrugs for NDT against bovine serum albumin as a model protein. Thus, we examined, among our developed boron tracedrugs, a boron-containing curcuminoid derivative UTX-51, to destroy freshly isolated human LDL dynamically under irradiated thermal neutron to obtain a decreased intensity of band of LDL treated with UTX-51 and thermal neutron irradiation in their SDS-PAGE and electrophoresis analysis. These results suggest that UTX-51 might be a novel candidate of 'beyond chemical' therapeutic agents for atherosclerotic cardiovascular disease.

Cumulative radiation dose from medical imaging in chronic adult patients.

Chronic patients require ongoing care that results in repeated imaging and exposure to ionizing radiation for both diagnostic and therapeutic purposes. This is of concern due to the long-term effects of radiation exposure, namely the association between radiation and increased cancer risk. In this study, the scientific literature on cumulated dose of radiation accrued from medical imaging by 4 cohorts of chronic patients (cardiac disease, end-stage kidney disease, inflammatory bowel disease, and patients undergoing endovascular aortic repair) was systematically reviewed. We found that the cumulative effective dose is moderate in cardiac and inflammatory bowel disease patients, high in end-stage kidney disease patients, and very high in endovascular aortic repair patients. We concluded that radiation burden of medical imaging is high in selected cohorts of chronic patients. Efforts should be implemented to reduce this cumulative dose and its potential attendant risks.

Trends of increasing medical radiation exposure in a population hospitalized for cardiovascular disease (1970-2009).

BACKGROUND: High radiation doses employed in cardiac imaging may increase cancer frequency in exposed patients after decades. The aim of this study was to evaluate the relative trends in medical radiation exposure in a population hospitalized for cardiovascular disease. METHODS AND RESULTS: An observational single-center study was conducted to examine 16,431 consecutive patients with heart disease admitted to the Italian National Research Council Institute of Clinical Physiology between January 1970 and December 2009. In all patients, the cumulative estimated effective dose was obtained from data mining of electronic records of hospital admissions, adopting the effective dose typical values of the American Heart Association 2009 statement and Mettler's 2008 catalog of doses. Cumulative estimated effective dose per patient in the last 5 years was 22 (12-42) mSv (median, 25(th)-75(th) percentiles), with higher values in ischemic heart disease (IHD), 37 (20-59) vs non-IHD, 13 (8-22) mSv, p<0.001. Trends in radiation exposure showed a steady increase in IHD and a flat trend in non-IHD patients, with variation from 1970-74 to 2005-2009 of +155% for IHD (p<0.001) and -1% in non-IHD (NS). The relative contribution of different imaging techniques was remodeled over time, with nuclear cardiology dominating in 1970s (23% of individual exposure) and invasive fluoroscopy in the last decade (90% of individual exposure). CONCLUSION: A progressive increase in cumulative estimated effective dose is observed in hospitalized IHD patients. The growing medical radiation exposure may encourage a more careful justification policy regarding ionizing imaging in cardiology patients applying the two main principles of radiation protection: appropriate justification for ordering and performing each procedure, and careful optimization of the radiation dose used during each procedure.

Measurement of insulin resistance in chronic kidney disease.

PURPOSE OF REVIEW: Insulin resistance is a known complication of end-stage renal disease that also appears to be present in earlier stages of chronic kidney disease (CKD). It is a risk factor for cardiovascular disease and an important potential therapeutic target in this population. Measurement of insulin resistance is reviewed in the context of known pathophysiologic abnormalities in CKD. RECENT FINDINGS: Insulin resistance in CKD is due to a high prevalence of known risk factors (e.g. obesity) and to unique metabolic abnormalities. The site of insulin resistance in CKD is localized to skeletal muscle. Estimates based on fasting insulin concentration may not adequately capture insulin resistance in CKD because they largely reflect hepatic defects and because CKD impairs insulin catabolism. A variety of dynamic tests are available to directly measure insulin-mediated glucose uptake. SUMMARY: Insulin resistance may be an important therapeutic target in CKD. Complementary methods are available to assess insulin resistance, and each method has unique advantages, disadvantages, and levels of complexity. These characteristics, and the likelihood that CKD alters the performance of some insulin resistance measurements, must be considered when designing and interpreting clinical studies.

Extracorporeal shock wave therapy as a new and non-invasive angiogenic strategy.

Ischemic heart disease is the leading cause of death and the number of refractory severe patients is increasing. Therefore, it is crucial to develop new therapeutic strategies for severe ischemic heart disease. We found that a low-energy shock wave (SW) (about 10% of energy density that used for urolithiasis) effectively increases the expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. Based on this in vitro study, we have started in vivo studies and have demonstrated that extracorporeal cardiac shock wave therapy with a low-energy SW upregulates the expression of VEGF, induces neovascularization, and improves myocardial ischemia in a porcine model of chronic myocardial ischemia without any adverse effects in vivo. On the basis of the promising results in animal studies, we have subsequently developed a new, non-invasive angiogenic therapy with low-energy SW for ischemic heart disease. Our extracorporeal cardiac SW therapy improved symptoms and myocardial perfusion evaluated with stress-scintigraphy in patients with severe coronary artery disease without indication of percutaneous coronary intervention or coronary bypass surgery. Importantly, no procedural complications or adverse effects were noted. The SW therapy was also effective to ameliorate LV remodeling after acute myocardial infarction in pigs and to enhance angiogenesis in hindlimb ischemia in rabbits. Based on these animal studies, we are also conducting clinical studies in patients with acute myocardial infarction and those with peripheral artery disease. Thus, our extracorporeal cardiac SW therapy is an effective, safe, and non-invasive angiogenic strategy in cardiovascular medicine and its indication is now rapidly expanding.

Cardiovascular studies and the radiation dose.

In a previous editorial, I commented on ionizing radiation associated with multislice computed tomographic angiography and x-ray coronary angiography performed in the catheterization laboratory. I mentioned that just by living, all of us are exposed to a background radiation dose, probably in the neighborhood of 3.6 millisieverts per year.

Severity of cardiovascular disease and health-related quality of life in men with prostate cancer: a longitudinal analysis from CaPSURE.

OBJECTIVE: To evaluate the influence of comorbid cardiovascular disease severity on health-related quality of life (HRQL) in men treated with radical prostatectomy (RP) or radiotherapy (RT) for early stage prostate cancer. METHODS: Subjects (n=830) with non-metastatic disease who had been diagnosed in 2000-2002 were drawn from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). We evaluated the influence of cardiovascular disease (CVD) severity on generic and disease-specific HRQL before and 6, 12, 18, and 24 months after treatment with RP or RT. HRQL was measured with the SF-36 and the UCLA Prostate Cancer Index. RESULTS: Men with moderate (n=193) or severe (n=51) cardiovascular disease had worse pre-treatment HRQL than did men without CVD (n=293) (P<0.01); HRQL scores were worse in men referred for RT. During 24 months of follow-up, men with moderate or severe CVD had worse SF-36 physical and mental component summaries and worse bowel function at all time points (P<0.05). Men with severe CVD also experienced a slower recovery in physical function (P=0.03) and sexual functioning (P=0.02) than did men without CVD. CONCLUSIONS: Prostate cancer patients with moderate to severe CVD have worse HRQL during follow-up. Those with severe CVD recover their physical and sexual functioning more slowly after treatment.

Interventional radiology procedures: addressing the needs of the cardiovascular patient.

Interventional radiologists perform a wide range of procedures on virtually every organ system in the body. Technological advances continue to expand the repertoire of procedures in this field, challenging the frontiers of medical science and individual expertise. With cardiovascular disease being the number 1 cause of death in the United States and an aging population before us, physicians who perform minimally invasive procedures must be knowledgeable regarding unique aspects of cardiovascular management as it pertains to the catheterization laboratory. Specific areas addressed in this review include anesthesia, hypertension, and chronic kidney disease.

Interventional cardiovascular procedures in Belgium: effective dose and conversion factors.

Effective dose (E), representing the risk of late radiation-induced effects, can be estimated by the use of conversion factors (CF), converting direct measurable quantities such as dose-area-product into E. Eight Belgian hospitals participated in the study with a total number of 318 procedures. E-values, calculated with PCXMC, were compared for the different hospitals for diagnostic and therapeutic procedures separately. E-values varied significantly depending on the hospital where the procedure was performed (P < 0.001), on filtration insertion (P < 0.001), on whether a centre is a training centre or not, the dose conscious action of the cardiologists and the complexity of the procedure (P < 0.001). Hospital-specific CF were calculated. An average CF of 0.185 mSv Gycm(-2) was obtained with a satisfactory correlation (r = 0.966, P < 0.001). The differences in CF between hospitals were due to, a large extent, the availability of additional filtration in cinegraphy mode (P < 0.001) and not to the differences in irradiation geometries in the clinical protocol of the interventional procedures.