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1.
Microbubble Formulations: Synthesis, Stability, Modeling and Biomedical Applications.
Upadhyay, A, Dalvi, SV
Ultrasound in medicine & biology. 2019;(2):301-343
Abstract
Microbubbles are increasingly being used in biomedical applications such as ultrasonic imaging and targeted drug delivery. Microbubbles typically range from 0.1 to 10 µm in size and consist of a protective shell made of lipids or proteins. The shell encapsulates a gaseous core containing gases such as oxygen, sulfur hexafluoride or perfluorocarbons. This review is a consolidated account of information available in the literature on research related to microbubbles. Efforts have been made to present an overview of microbubble synthesis techniques; microbubble stability; microbubbles as contrast agents in ultrasonic imaging and drug delivery vehicles; and side effects related to microbubble administration in humans. Developments related to the modeling of microbubble dissolution and stability are also discussed.
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Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study).
Karakatsanis, A, Hersi, AF, Pistiolis, L, Olofsson Bagge, R, Lykoudis, PM, Eriksson, S, Wärnberg, F, ,
The British journal of surgery. 2019;(6):720-728
Abstract
BACKGROUND One-fifth of patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) have invasive breast cancer (IBC) on definitive histology. Sentinel lymph node dissection (SLND) is performed in almost half of women having surgery for DCIS in Sweden. The aim of the present study was to try to minimize unnecessary SLND by injecting superparamagnetic iron oxide (SPIO) nanoparticles at the time of primary breast surgery, enabling SLND to be performed later, if IBC is found in the primary specimen. METHODS Women with DCIS at high risk for the presence of invasion undergoing breast conservation, and patients with DCIS undergoing mastectomy were included. The primary outcome was whether this technique could reduce SLND. Secondary outcomes were number of SLNDs avoided, detection rate and procedure-related costs. RESULTS This was a preplanned interim analysis of 189 procedures. IBC was found in 47 and a secondary SLND was performed in 41 women. Thus, 78·3 per cent of patients avoided SLND (P < 0·001). At reoperation, SPIO plus blue dye outperformed isotope and blue dye in detection of the sentinel node (40 of 40 versus 26 of 40 women; P < 0·001). Costs were reduced by a mean of 24·5 per cent in women without IBC (€3990 versus 5286; P < 0·001). CONCLUSION Marking the sentinel node with SPIO in women having surgery for DCIS was effective at avoiding unnecessary SLND in this study. Registration number: ISRCTN18430240 (http://www.isrctn.com).
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Prophylactic atorvastatin prior to intra-arterial administration of iodinated contrast media for prevention of contrast-induced acute kidney injury: A meta-analysis of randomized trial data
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Sun, YY, Liu, LY, Sun, T, Wu, MY, Ma, FZ
Clinical nephrology. 2019;(3):123-130
Abstract
BACKGROUND The efficacy of high-dose atorvastatin pretreatment in reducing the incidence of contrast-induced nephropathy in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) has been examined in some randomized studies. However, the results across the trials remain controversial. OBJECTIVE This study sought to perform a meta-analysis to evaluate the effect of high-dose atorvastatin in the prevention of contrast-induced nephropathy (CIN) while undergoing CAG or PCI. MATERIALS AND METHODS Comprehensive literature searches for randomized controlled trials (RCTs) comparing high-dose atorvastatin vs. low-dose statin or placebo pretreatment for prevention of contrast-induced acute kidney injury in patients undergoing CAG were performed using PubMed, Embase, and the Cochrane library updated to June 2017. The primary outcome was the incidence of CIN. RESULTS A total of 11 RCTs were included in this analysis. The high-dose atorvastatin treatment can significantly reduce the incidence of CIN (OR 0.46, 95% CI 0.35 - 0.62, p < 0.00001). The benefit was consistent in comparison with the low-dose group (OR 0.41, 95% CI 0.25 - 0.66, p = 0.0003) and the placebo group (OR 0.50, 95% CI 0.26 - 0.98, p = 0.04). CONCLUSION Our study demonstrates that high-dose statin pretreatment shows a benefit specifically in reducing the incidence of contrast-induced acute kidney injury in patients undergoing CAG, especially compared with low-dose statin pretreatment.
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4.
Contrast Material Injection Protocol With the Dose Determined According to Lean Body Weight at Hepatic Dynamic Computed Tomography: Comparison Among Patients With Different Body Mass Indices.
Matsumoto, Y, Masuda, T, Sato, T, Arataki, K, Nakamura, Y, Tatsugami, F, Awai, K
Journal of computer assisted tomography. 2019;(5):736-740
Abstract
OBJECTIVE The objective of this study was to compare enhancement of the aorta and liver on hepatic dynamic computed tomography scans acquired with contrast material doses based on the lean body weight (LBW) or the total body weight (TBW). METHODS We randomly divided 529 patients (279 men, 250 women; median age, 66 years) scheduled for hepatic dynamic computed tomography into 2 groups. The LBW patients (n = 278) were injected with 679 mg iodine/kg (men) or 762 mg iodine/kg (women). The TBW group (n = 251) was injected with 600 mg iodine/kg TBW. Each group was subdivided into the 3 classes based on the body mass index (BMI; low, normal, high). Aortic enhancement during the hepatic arterial phase and hepatic enhancement during the portal venous phase was compared. The aortic and hepatic equivalence margins were 100 and 20 Hounsfield units, respectively. RESULTS Comparison of the median iodine dose in patients with a normal or high BMI showed that it was significantly lower under the LBW protocol than the TBW protocol (558.2 and 507.0 mg iodine/kg, P < 0.001, respectively). However, in patients with a low BMI, the LBW protocol delivered a significantly higher dose than the TBW protocol (620.7 vs 600.0 mg iodine/kg, P < 0.001). The 95% confidence interval for the difference in aortic and hepatic enhancement between the 2 protocols was within the range of the predetermined equivalence margins in all BMI subgroups. CONCLUSIONS Contrast enhancement was equivalent under both protocols. The LBW protocol can avoid iodine overdosing, especially in patients with a high BMI.
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Comparison of double-dose vs. usual dose of nicorandil for the prevention of contrast-induced nephropathy after cardiac catheterization.
Zeng, Z, Fu, X, Zhang, X, Fu, N
International urology and nephrology. 2019;(11):1999-2004
Abstract
PURPOSE Contrast-associated nephropathy (CIN), the third main reason of the acute kidney injury (AKI) in inpatients, is a potentially severe side effect of angiography and the preventive role of nicorandil on CIN is still controversal. The aim of this clinical trial was to evaluate the preventive role of different doses of nicorandil on CIN in patients experiencing cardiac catheterization compared with hydration. METHODS We recorded outcomes from 330 patients who were randomly divided to either a double-dose (30 mg/day) nicorandil group or to a usual-dose (15 mg/day) nicorandil group or a control group (hydration only). The primary endpoint of the current research was the occurrence of CIN, which is defined as a relative elevation of SCr level of 25% above the baseline or an absolute increment of SCr of more than 44.2 µmol/L (0.5 mg/dL) within 48 or 72 h after contrast medium exposure. Additional endpoints were the changes in BUN, SCr, Cys-C, eGFR, and CRP level within 48 h after contrast agent exposure and major adverse events occurring during hospitalization and 14 days of follow-up. RESULTS 6 out of 111 patients (5.4%) had contrast-induced nephropathy in the double-dose group and it occured 11 out of 107 patients (10.3%) in the usual-dose group, 16 out of 112 patients (14.3%) in the control group. There was a significant difference in the occurrence of CIN between the double-dose group and the control group at 48 h after taking the radiocontrast medium (p = 0.026) while no such significant difference observed in the usual-dose group and the control group (p = 0.367), the double-dose group and usual-dose group (p = 0.180) as well. CONCLUSIONS Daily peri-procedural usual-dose nicorandil could just relieve contrast-induced renal injury, only double-dose nicorandil was associated with a reduced incidence of CI-AKI compared with hydration.
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Meta-analysis on allopurinol preventive intervention on contrast-induced acute kidney injury with random controlled trials: PRISMA.
Ma, G, Wang, G, Xiao, D, Teng, W, Hui, X, Ma, G
Medicine. 2019;(25):e15962
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Abstract
OBJECTIVES The objective of this meta-analysis on randomized controlled trials is to evaluate whether the administration of allopurinol with or without hydration will reduce contrast-induced acute kidney injury (CI-AKI) in patients undergoing contrast exposure. BACKGROUND The efficacy of allopurinol in the prevention of CI-AKI after cardiac catheterization and percutaneous coronary intervention (PCI) is significantly related to the heterogeneous results. METHODS Two investigators independently searched MEDLINE, EMBASE, the Cochrane Controlled Trials Registry, the China Wanfang Data, the China Biological Medicine Database and the China National Knowledge Infrastructure (CNKI) databases for randomized controlled trials (RCTs) comparing allopurinol with placebo or no allopurinol for the prevention of CI-AKI in patients from their inception to July 31, 2018. The primary outcome was the incidence of CI-AKI, and the secondary outcomes were the differences of serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), and estimated glomerular filtration rate (eGFR) levels between groups after contrast media exposure. We used fixed-effects or random-effects models according to I statistics. The meta-analytic procedures were completed by Review Manager, version 5.3. ACHIEVEMENTS Eight random controlled trials with 1141 patients were included for this analysis. Compared with the control, allopurinol was associated with a reduced risk of CI-AKI (Relatives Risk (RR) 0.39, 95% confidence interval [CI] 0.20,0.74, P = .004) and only a intend for decrease a post-procedure uric acid levels compared with the controlled ones at 48 hours (standardized mean difference (SMD) -0.72, 95% CI -1.44, 0.01, P = .05). But the difference of post-procedure uric acid levels was not statistically significant in allopurinol groups compared with controlled groups. There were lower post-procedure Scr and BUN levels in allopurinol groups than those in controlled groups (SMD -0.50, 95% CI -0.79,-0.21, P = .0009; SMD -0.40, 95% CI -0.60,-0.20, P < .0001;respectively). There were higher post-procedure eGFR levels in allopurinol groups than those in controlled groups (SMD 0.65, 95% CI 0.48, 0.83, P < .0001). CONCLUSION The main findings of this meta-analysis are focus on allopurinol may cause reduces in the incidence of CI-AKI in patients undergoing interventional coronary procedures. Further researches are still required for confirmation.
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Effect of Alprostadil on the Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of 36 Randomized Controlled Trials.
Xie, J, Jiang, M, Lin, Y, Deng, H, Li, L
Angiology. 2019;(7):594-612
Abstract
Contrast-induced nephropathy (CIN) is the third leading cause of acquired acute renal injury in hospitalized patients. Alprostadil plays a role in the maintenance and redistribution of intrarenal blood flow and the excretion of electrolytes and water. However, the effectiveness of alprostadil in preventing CIN remains controversial. Thirty-six articles with a total of 5495 patients were included in this study. Both groups (experimental group and control group) received standard hydration therapy. In the experimental group, patients received different doses of alprostadil. Serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), cystatin C, creatinine clearance rate (CCr), and β2-microglobulin (β2-MG) were measured at 24, 48, and 72 hours after contrast media injection. The incidence of CIN in the experimental group was significantly lower than that in the control group (6.56% vs 16.74%). The level of SCr, cystatin C, BUN, and β2-MG in the experimental group was lower than those in the control group; CCr and eGFR in the experimental group were higher than those in the control group. This study demonstrated that alprostadil may reduce the incidence of CIN in patients undergoing coronary angiogram and/or percutaneous coronary intervention.
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Magnetic Particle Imaging-Guided Stenting.
Herz, S, Vogel, P, Kampf, T, Dietrich, P, Veldhoen, S, Rückert, MA, Kickuth, R, Behr, VC, Bley, TA
Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists. 2019;(4):512-519
Abstract
Purpose:To assess the feasibility of magnetic particle imaging (MPI) to guide stenting in a phantom model. Materials and Methods: MPI is a new tomographic imaging method based on the background-free magnetic field detection of a tracer agent composed of superparamagnetic iron oxide nanoparticles (SPIOs). All experiments were conducted on a custom-built MPI scanner (field of view: 29-mm diameter, 65-mm length; isotropic spatial resolution 1-1.5-mm). Stenosis phantoms (n=3) consisted of polyvinyl chloride (PVC) tubes (8-mm inner diameter) prepared with centrally aligned cable binders to form a ~50% stenosis. A dedicated image reconstruction algorithm allowed precise tracking of endovascular instruments at 8 frames/s with a latency time of ~115 ms. A custom-made MPI-visible lacquer was used to manually label conventional guidewires, balloon catheters, and stainless steel balloon-expandable stents. Vascular stenoses were visualized by injecting a diluted SPIO tracer (ferucarbotran, 10 mmol iron/L) into the vessel phantoms. Balloon angioplasty and stent placement were performed by inflating balloon catheters and stent delivery balloons with diluted ferucarbotran. Results: After deployment of the stent, the markers on its ends were clearly visible. The applied lacquer markers were thin enough to not relevantly alter gliding properties of the devices while withstanding friction during the experiments. Placing an optimized flexible lacquer formulation on the preexisting radiopaque stent markers provided enough stability to withstand stent expansion. Final MPA confirmed successful stenosis treatment, facilitated by the disappearance of the lacquer markers on the stent due to differences in SPIO concentration. Thus, the in-stent lumen could be visualized without interference by the signal from the markers. Conclusion: Near real-time visualization of MPI-guided stenting of stenoses in a phantom model is feasible. Optimized MPI-visible markers can withstand the expansion process of stents.
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Manganese Oxide Nanoparticles As MRI Contrast Agents In Tumor Multimodal Imaging And Therapy.
Cai, X, Zhu, Q, Zeng, Y, Zeng, Q, Chen, X, Zhan, Y
International journal of nanomedicine. 2019;:8321-8344
Abstract
Contrast agents (CAs) play a crucial role in high-quality magnetic resonance imaging (MRI) applications. At present, as a result of the Gd-based CAs which are associated with renal fibrosis as well as the inherent dark imaging characteristics of superparamagnetic iron oxide nanoparticles, Mn-based CAs which have a good biocompatibility and bright images are considered ideal for MRI. In addition, manganese oxide nanoparticles (MONs, such as MnO, MnO2, Mn3O4, and MnOx) have attracted attention as T1-weighted magnetic resonance CAs due to the short circulation time of Mn(II) ion chelate and the size-controlled circulation time of colloidal nanoparticles. In this review, recent advances in the use of MONs as MRI contrast agents for tumor detection and diagnosis are reported, as are the advances in in vivo toxicity, distribution and tumor microenvironment-responsive enhanced tumor chemotherapy and radiotherapy as well as photothermal and photodynamic therapies.
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Early Predictors of the Long-term Response to Therapy in Patients With Crohn Disease Derived From a Time-Intensity Curve Analysis After Microbubble Contrast Agent Injection.
Quaia, E, Gennari, AG, Cova, MA
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2019;(4):947-958
Abstract
OBJECTIVES The aim of this study was to identify early predictors of the long-term response to therapy in patients with Crohn disease (CD) from time-intensity curves obtained after microbubble injection. METHODS One hundred fifteen consecutive patients with a proven diagnosis of CD involving the terminal ileal loop who were scheduled to begin pharmacologic therapy with biologics (infliximab or adalimumab) were scanned after sulfur hexafluoride-filled microbubble injection before the beginning and at the end of the sixth week of treatment. The absolute value and percentage change of each semiquantitative kinetic parameter (peak enhancement, time to peak enhancement, rise time, mean transit time, wash-in and wash-out rates, area under the curve [AUC] for the whole time-intensity curve, AUC during wash-in, AUC during wash-out, and wash-in perfusion index) as measured on the terminal ileal tract and adjacent reactive mesenteric fat were calculated from time-intensity curves. Patients were followed for at least 24 months with redetermination of the Crohn Disease Activity Index and with at least 1 endoscopy within 18 weeks after the beginning of pharmacologic treatment. The absolute values and percentage changes of kinetic parameters were assessed as potential predictors of the therapeutic outcome by a logistic regression analysis. RESULTS The study group included 66 male and 49 female patients (mean age ± SD, 45.76 ± 11 years). The pretreatment values and percentage changes of the peak enhancement, AUC, AUC during wash-in, and AUC during wash-out were found to be predictors (P < .05) of the long-term therapeutic outcome. CONCLUSIONS The analysis of time-intensity curves obtained after microbubble contrast agent injection provides early predictors of the long-term therapeutic outcome in patients with CD.