Microvascular changes following exposure to iodinated contrast media in vitro. A qualitative comparison to serum creatinine concentrations in post-cardiac catheterization patients.

INTRODUCTION: Contrast-associated acute kidney injury (CA-AKI) is characterized as a loss of renal function following radiological contrast media administration. While all contrast media induce variable changes in microvascular endothelial cells in vitro, only few studies report clinical significance of their findings. A comprehensive assessment of the effect of iodinated contrast media on the renal function in vitro and in vivo is essential. The aim of our study was to morphometrically quantify the effect of two different contrast media (Iobitridol and Iodixanol) on vascular endothelial capillaries in vitro and to analyze their effect on the renal function of patients who underwent cardiac catheterization including the intra-arterial administration of contrast media, by measuring serum creatinine concentration (SCr), a byproduct of muscle metabolism, primarily excreted by the kidneys. Our hypothesis suggests that conducting a qualitative comparison of both outcomes will enable identification of differences and similarities between in vitro and in vivo exposure. MATERIAL AND METHODS: In vitro, co-cultures of human dermal fibroblasts and human dermal microvascular endothelial cells forming capillary beds were exposed to a mixture of phosphate buffered saline and either Iobitridol, Iodixanol, or one of their supplements EDTA or Trometamol for 1.5 or 5 min. Negative control co-cultures were exposed exclusively to phosphate buffered saline. Co-cultures were either directly fixed or underwent a regeneration time of 1, 3 or 7 days. An artificial intelligence software was trained for detection of labeled endothelial capillaries (CD31) on light microscope images and measurements of morphometric parameters. In vivo, we retrospectively analyzed data from patients who underwent intra-arterial administration of contrast media and for whom SCr values were available pre- and post-contrast exposition (1, 3, and 7 days following procedure). Temporal development of SCr and incidence of CA-AKI were assessed. Both exposure types were qualitatively compared. RESULTS: In vitro, Iobitridol, Iodixanol and EDTA induced a strong decrease of two morphometric parameters after 3 days of regeneration. In vivo, a significant increase of SCr and incidence of CA-AKI was observed 3 days following procedure in the post-contrast media patients. No difference was observed between groups. DISCUSSION: Two of the morphometric parameters were inversely proportional to the SCr of the patients. If the endothelial damages observed in vitro occur in vivo, it may result in renal hypoxia, inducing a loss of kidney function clinically translated into an increase of SCr. Further development of our in vitro model could allow closer replication of the internal structure of a kidney and bridge the gap between in vitro studies and their clinical findings.

A randomized comparison of a novel iopromide-based paclitaxel-coated balloon Shenqi versus SeQuent Please for the treatment of in-stent restenosis.

BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging in contemporary clinical applications. Drug-coated balloon (DCB) angioplasty offers an effective treatment for ISR. Shenqi is a novel iopromide-based paclitaxel-coated balloon and its clinical safety, effectiveness and angiographic efficacy in patients with ISR have not been investigated. METHODS: A total of 216 subjects with the first occurrence of ISR at 11 investigational sites in China were randomly allocated in a 1:1 fashion to treatment with DCB SeQuent Please or Shenqi. Clinical follow-up was planned at 1, 6, 9 and 12 months, and angiographic follow-up was planned at 9 months. The study was powered for the primary endpoint of 9-month in-segment late loss. RESULTS: At 9-month follow-up, the in-segment late loss was 0.29 ± 0.43 mm with Shenqi versus 0.30 ± 0.46 mm with SeQuent Please, and the one-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of Shenqi compared with SeQuent Please (P = 0.002). In total, 12 patients developed target lesion failure (TLF) in the Shenqi group compared with 16 patients in the SeQuent Please group (10.91% versus 15.09%; P = 0.42) within 1 year. TLF was mainly driven by target lesion revascularization (9.09%) followed by target vessel-related myocardial infarction (1.82%) and cardiovascular death (0.91%) in the Shenqi group. CONCLUSIONS: Shenqi DCB was noninferior to SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. Shenqi DCB may become an attractive alternative treatment for patients with coronary ISR, withholding the need for additional stent implantation.

Synthesis of Bi2WO6-x nanodots with oxygen vacancies as an all-in-one nanoagent for simultaneous CT/IR imaging and photothermal/photodynamic therapy of tumors.

All-in-one nanoagents with a single-component and all-required functions have attracted increasing attention for the imaging-guided therapy of tumors, but the design and preparation of such nanoagents remain a challenge. Herein, we report the introduction of oxygen vacancies to traditional semiconductors with heavy-metal elements for tuning photoabsorption in the near infrared (NIR) region, by using Bi2WO6 (band-gap: ∼2.7 eV) as a model. Bi2WO6-x nanodots with sizes of ∼3 or ∼8 nm have been prepared by a facile coprecipitation-solvothermal method assisted by citric acid (CA, 0.1-1.5 g) as the reduction agent. CA confers the removal of O atoms from the [Bi2O2]2+ layer during the solvothermal process, resulting in the formation of plenty of oxygen vacancies in the Bi2WO6-x crystal. As a result, NIR photoabsorption of Bi2WO6-x nanodots can be remarkably enhanced with the increase of the CA amount from 0 to 1.0 g. Under irradiation of a single-wavelength (808 nm, 1.0 W cm-2) NIR laser, black Bi2WO6-x-CA1.0 nanodots can not only efficiently produce a sufficient amount of heat with a photothermal conversion efficiency of 45.1% for photothermal therapy, but also generate singlet oxygen (1O2) for photodynamic therapy. Furthermore, due to the presence of heavy-metal (Bi and W) elements, Bi2WO6-x-CA1.0 nanodots have high X-ray attenuation ability for CT imaging. After the Bi2WO6-x-CA1.0 nanodot dispersion is injected into the tumor-bearing mice, the tumor can be imaged by using CT and an IR thermal camera. After irradiation with a single-wavelength (808 nm, 1.0 W cm-2, 10 min) NIR laser, the tumor can be completely suppressed by the synergic photothermal and photodynamic effects of Bi2WO6-x-CA1.0 nanodots, without recurrence and treatment-induced toxicity. Therefore, Bi2WO6-x nanodots have great potential as a novel all-in-one nanoagent for the imaging and phototherapy of tumors.

Iodixanol versus Iopromide at Coronary CT Angiography: Lumen Opacification and Effect on Heart Rhythm-the Randomized IsoCOR Trial.

Purpose To show that equal coronary lumen opacification can be achieved with iso- and low-osmolar contrast media when it is injected at the same iodine delivery rate with contemporary cardiac computed tomographic (CT) protocols and to investigate the cardiovascular effect of iso-osmolar contrast media and the image quality achieved. Materials and Methods Institutional review board approval and written informed consent were obtained for the Effect of Iso-osmolar Contrast Medium on Coronary Opacification and Heart Rhythm in Coronary CT Angiography, or IsoCOR, trial. Between November 2015 and August 2016, 306 patients (167 [55%] women) at least 18 years old (weight range, 50-125 kg), were prospectively randomized to receive iso-osmolar iodixanol 270 or low-osmolar iopromide 300 contrast media. All coronary segments were assessed for intraluminal opacification and image quality and were compared by using the Student t test. Heart rate, arrhythmia, patient discomfort, and adverse events also were monitored. Results Mean measured coronary attenuation values ± standard deviation were comparable between the iodixanol 270 and iopromide 300 contrast media groups (469 HU ± 167 vs 447 HU ± 166, respectively [P = .241]; 95% confidence interval: -15.1, 60.0), including those from subanalyses. Adjusted for the lower iodine concentration, the mean iodixanol 270 bolus was larger compared with that of iopromide 300 (76.8 mL ± 11.6 vs 69.7 mL ± 10.8, respectively; P < .001). The higher injection rate was associated with higher pressure (777 kPa ± 308 vs 630 kPa ± 252, respectively; P < .001). Although in the iodixanol 270 group patients experienced less heat discomfort (72% vs 86%, respectively; P < .001), no differences in heart rate or rhythm were observed. Conclusion If injected at comparable iodine delivery rates, the iso-osmolar contrast medium iodixanol 270 is not inferior to low-osmolar contrast medium iopromide 300 for assessment of coronary opacification. Iodixanol 270 was associated with less heat discomfort, but did not affect heart rate differently compared with iopromide 300. © RSNA, 2017 Online supplemental material is available for this article.

Increased image quality and reduced radiation dose and contrast media volume: a holistic approach to intracranial CTA.

AIM: To investigate the dose-length product (DLP) during intracranial computed tomography angiography (CTA) using a patient-specific contrast formula. MATERIALS AND METHODS: Intracranial CTA was performed on 120 patients using 64-channel CT. Patients were subjected in equal numbers to one of two acquisitions/contrast medium protocols. Protocol A, consisted of 80 ml contrast medium and protocol B, involved a novel contrast medium formula. In each protocol, contrast medium and saline were injected at a flow rate of 4.5 ml/s. The DLP and contrast volume (CV) were measured between each protocol and the data obtained were compared using two-tailed independent t-test. RESULTS: Mean arterial vessel attenuation was up to 56% (p<0.01) higher using protocol B compared with A. In the venous system, the mean vessel attenuation was significantly lower in protocol B than A with a maximum reduction of 93% (p<0.001). The mean CV was significantly lower in protocol B (53±10 ml) compared to A (80±1 ml, p<0.001). The scan time was equal in each protocol (B, 4.22±1.2 seconds; A, 4.01±1.3 seconds). A significant reduction in mean DLP was demonstrated in protocol B (3.99±0.22 mSv) compared to A (4.74±0.22 mSv; p=0.02). CONCLUSION: A significant reduction in CV and DLP during intracranial CTA can be achieved when employing a patient-specific contrast medium formula.

Incidental physiological sliding hiatal hernia: a single center comparison study between CT with water enema and CT colonography.

PURPOSE: Hiatal hernia is a well-known factor impacting on most mechanisms underlying gastroesophageal reflux, related with the risk of developing complications such as erosive esophagitis, Barrett's esophagus and ultimately, esophageal adenocarcinoma. It is our firm opinion that an erroneous reporting of hiatal hernia in CT exams performed with colonic distention may trigger a consecutive diagnostic process that is not only unnecessary, inducing a unmotivated anxiety in the patient, but also expensive and time-consuming for both the patient and the healthcare system. The purposes of our study were to determine whether colonic distention at CT with water enema and CT colonography can induce small sliding hiatal hernias and to detect whether hiatal hernias size modifications could be considered significant for both water and gas distention techniques. METHODS: We retrospectively evaluated 400 consecutive patients, 200 undergoing CT-WE and 200 undergoing CTC, including 59 subjects who also underwent a routine abdominal CT evaluation on a different time, used as internal control, while a separate group of 200 consecutive patients who underwent abdominal CT evaluation was used as external control. Two abdominal radiologists assessed the CT exams for the presence of a sliding hiatal hernia, grading the size as small, moderate, or large; the internal control groups were directly compared with the corresponding CT-WE or CTC study looking for a change in hernia size. We used the Student's t test applying a size-specific correction factor, in order to account for the effect of colonic distention: these "corrected" values were then individually compared with the external control group. RESULTS: A sliding hiatal hernia was present in 51 % (102/200) of the CT-WE patients and in 48.5 % (97/200) of the CTC patients. Internal control CT of the 31 patients with a hernia at CT-WE showed resolution of the hernia in 58.1 % (18/31) of patients, including 76.5 % (13/17) and 45.5 % (5/11) of small and moderate hernias. Comparison CT of the 28 patients with a hiatal hernia at CTC showed the absence of the hernia in 57.1 % (16/28) patients, including 68.8 % (11/16) and 50 % (5/10) of small and moderate hernias. The prevalence of sliding hiatal hernias in the external control group was 22 % (44/200), significantly lower than the CT-WE and CTC cohorts' prevalence of 51 % (p < 0.0001) and 48.5 % (p < 0.0001). After applying the correction factors for the CT-WE and the CTC groups, the estimated residual prevalences (16 and 18.5 %, respectively) were much closer to that of the external control patients (p = 0.160 for CT-WE and p = 0.455 for CTC). CONCLUSIONS: We believe that incidental findings at CT-WE and CTC should be considered according to the clinical background, and that small sliding hiatal hernias should not be reported in patients with symptoms not related to reflux disease undergoing CT-WE or CTC: When encountering these findings, accurate anamnesis and review of medical history looking for GERD-related symptoms are essential, in order to address these patients to a correct diagnostic iter, taking advantage from more appropriate techniques such as endoscopy or functional techniques.

Local delivery of paclitaxel in the treatment of peripheral arterial disease.

BACKGROUND: Despite advancements from balloon angioplasty to drug-eluting stents, primary patency rates after endovascular revascularization of peripheral artery disease have remained inferior compared to surgery. Endovascular revascularization has been limited by restenosis and mechanical stent failure. Thus, there is increased research into other nonstent-based local drug delivery modalities, which can provide an active drug to inhibit restenosis focally and avoid the risk of systemic adverse effects. METHODS: This review will summarize the unique properties of paclitaxel and studies on paclitaxel local delivery for the treatment of peripheral artery disease. A MEDLINE search for relevant peer-reviewed scientific literature published in English was conducted. Search terms included but were not limited to paclitaxel pharmacodynamics, paclitaxel local drug delivery, and drug eluting balloons, with a focus on the use of paclitaxel in the context of coronary and peripheral vascular disease. RESULTS: The primary search produced 182 results of which 51 papers were relevant. Of the 51 relevant papers, 27 were original research papers and 24 were either review papers, commentary or opinion papers. CONCLUSIONS: Paclitaxel has several chemical properties, which make it ideal for local drug delivery including its hydrophobicity, ability to concentrate into the arterial intima layer and prolonged effect on cells even after brief exposure periods. Local delivery of paclitaxel via injection catheters, balloon catheters and coated balloons has shown encouraging results in terms of efficacy and safety in small-scale animal and clinical studies. Additional preclinical and clinical studies are needed to determine the long-term efficacy and safety of these treatments in humans.

Significant perturbation in renal functional magnetic resonance imaging parameters and contrast retention for iodixanol compared with iopromide: an experimental study using blood-oxygen-level-dependent/diffusion-weighted magnetic resonance imaging and computed tomography in rats.

OBJECTIVES: The objective of this study was to investigate the renal changes after intravenous administration of a high dose of either iodixanol or iopromide using functional magnetic resonance imaging (MRI) and computed tomography (CT). MATERIALS AND METHODS: The study was approved by the institutional committee on animal research. Seventy-two male Sprague-Dawley rats were divided into 5 cohorts, comprising normal saline (NS), iopromide, iopromide + NS, iodixanol, and iodixanol + NS. Intravenous contrast was administrated at 8 g iodine/kg of body weight. Renal CT, quantitative functional MRI of blood-oxygen-level-dependent (BOLD) imaging and diffusion-weighted imaging (DWI), and histologic examinations were performed for 18 days after contrast administration. Statistical analysis was performed by using 1-way analysis of variance, Mann-Whitney test, and regression analysis. RESULTS: In the renal cortex, BOLD showed persistent elevation of R2* and DWI showed persistent suppression of apparent diffusion coefficient after iodixanol administration for 18 days. Compared with iopromide, adjusted ΔR2* (ΔR2*adj) was significantly higher in the iodixanol group from 1 hour to 18 days (P < 0.04) after contrast; adjusted ΔADC (ΔADCadj) was significantly more pronounced at day 6 (P = 0.01) after contrast. The iodixanol cohort also exhibited persistently higher attenuation in the renal cortex on CT and more severe microscopic renal cortical vacuolization up to 18 days. Intravenous hydration decreased the magnetic resonance changes in both groups but more markedly with iodixanol. CONCLUSIONS: At high doses, iodixanol induced greater changes in renal functional MRI (BOLD and DWI) relative to iopromide. Combined with longer contrast retention within the kidney, this suggests that iodixanol may produce more severe and longer-lasting contrast-induced renal damage.

Accuracy of water-enema multidetector computed tomography (WE-MDCT) in colon cancer staging: a prospective study.

PURPOSE: To assess the accuracy of water-enema multidetector computed tomography (WE-MDCT) in extra-rectal colon cancer staging. MATERIALS AND METHODS: Fifty-three patients (mean age 70 years) with extra-rectal colon cancer proven by colonoscopy and biopsy were prospectively evaluated by preoperative WE-MDCT. CT scans were both intraluminal (water enema or WE) and intravenous (iodinated) contrast enhanced (CE). All patients underwent surgery. Tumors were classified with the TNM staging system. Noted CT features were: tumor size and location; tumor form and edges; spread to the pericolic fat or neighboring organs; thickening of retroperitoneal fascia; number, size, and enhancement of the peritumoral lymph nodes. Tumors were classified on CT into 3 T-stage groups: T1/T2, T3, and T4. Lymph nodes were classified by their density after injection [positive over 100 Hounsfield units (HU)]. RESULTS: Tumor localization to the specific colon segment was correct in all the cases. The agreement between WE-MDCT staging and histopathology staging was good (k = 0.64). An irregular and bowl-shaped aspect of the external edges of tumor provided excellent sensitivity for T3/T4 inclusion (Se 97.7%, NPV 85.7%). Thickening of a fascia or the abdominal wall provided good specificity for T4 stage (Sp 88.1%, NPV 94.9%). Enhancement over 100 HU of at least one peritumoral lymph node was the best criterion of N+ staging (Sp 67.7%, NPV 87.5%). CONCLUSION: WE-MDCT permits good staging of colon cancer based on objective features.

Refining the assessment of contrast-induced acute kidney injury: the load-to-damage relationship.

AIMS: Comparing the nephrotoxicity of individual contrast agents is challenging, as contrast-induced acute kidney injury (CI-AKI), a widely used trial endpoint, is unable to discriminate between contrast-related and contrast-unrelated causes of renal damage. We established a quantitative method to selectively evaluate the dose-dependent nephrotoxic effect of different contrast agents. METHODS: We randomized 113 patients undergoing coronary procedures to either iodixanol 320 mg/ml or iobitridol 350 mg/ml. We calculated baseline creatinine clearance (CrCl) and postprocedural change in serum creatinine. We then calculated the regression of the individual iodine load against the creatinine maximum change [load-to-damage relationship (LDR)]. We assumed that its R estimates the predictive accuracy of contrast dose-dependent effects on renal function changes, and that the slope of the LDR characterizes the intrinsic nephrotoxicity of the contrast. We also performed a semi-quantitative evaluation of procedural complexity to assess its complementary role in postprocedural AKI. RESULTS: We found significant correlations between contrast load and creatinine changes for both iobitridol (R: 0.29; P <0.0001) and iodixanol (R: 0.15; P = 0.00028). The LDR slope was, however, significantly steeper for iobitridol compared with iodixanol (19.03 ±â€Š4.02 vs. 14.50 ±â€Š4.63 Cr*CrCl/I; P <0.001) and in diabetic compared with nondiabetic patients (24.35 ±â€Š4.96 vs. 4.59 ±â€Š3.25 Cr*CrCl/I; P <0.001). Adding the procedural complexity score to the contrast load significantly increased the predictive ability of the regression model for postprocedural renal function changes (P < 0.02 for the R increase in overall population), suggesting a role for procedural complexity in postprocedural renal function damage. CONCLUSION: The LDR slope is a promising method to evaluate the specific contrast-related fraction of postprocedural AKI.

Intraarticular local anesthesia: can it reduce pain related to MR or CT arthrography of the shoulder?

OBJECTIVE: The objective of this study was to prospectively evaluate whether intraarticular anesthesia can reduce pain after MR or CT arthrography of the shoulder. SUBJECTS AND METHODS: This study included 120 patients who underwent CT or MR arthrography of the shoulder. The patients were randomized into two groups: the study group (n = 60), each administered an intraarticular injection of the contrast agent mixed with a local anesthetic (2% mepivacaine); and the control group (n = 60), each injected with the contrast agent only. Each patient's pain level was assessed at five phases-baseline and immediately, 2 hours, 1 day, and 2 days after injection-by using a visual analog scale or a verbal rating scale. The net pain score at each phase was also calculated. The pain course and net pain score were compared between study and control groups by repeated-measures analysis of variance. After the patients were divided into subgroups according to patient- or procedure-related factors, the efficacy of the intraarticular local anesthetic in each subgroup was evaluated. RESULTS: The pain course showed a quadratic trend and was not significantly different between study and control groups. The net pain score also was not significantly different between the two groups. No subgroup showed a significantly different efficacy of the intraarticular local anesthetic between the two groups. CONCLUSION: Intraarticular local anesthesia did not reduce arthrography-related pain.

Incompatibility of contrast medium and trisodium citrate.

PURPOSE: To test the compatibility of trisodium citrate, a catheter lock solution, with iodinated contrast medium. METHODS: Iohexol, iobitridol, iodixanol, ioxaglate, ioxithalamate, iomeprol, and iopromide were tested. In all tests, 2 ml of contrast medium were mixed with 2 ml of trisodium citrate solution. RESULTS: Iodixanol and ioxaglate provoked a highly viscous gluelike precipitation when mixed with trisodium citrate. A brief transient precipitate was observed with iohexol, iomeprol, and ioxithalamate. Permanent precipitation occurred with iobitridol and iopromide. CONCLUSION: One must be aware of the potential for precipitation when contrast medium is mixed with trisodium citrate solution. Before trisodium citrate solution is injected, the catheter should be thoroughly flushed with saline if a contrast medium has previously been injected through it.

Cost-effectiveness of iso- versus low-osmolality contrast media in outpatients with high risk of contrast medium-induced nephropathy.

INTRODUCTION: Contrast media can cause acute renal failure by direct toxic effects on the tubular cells and kidney ischemia. Diabetics and hospitalized patients have a greater risk of developing contrast-induced nephropathy than the general population. OBJECTIVE: The cost effectiveness of iso and low-osmolality contrast media was assessed in high risk outpatients. MATERIALS AND METHODS: The analysis was based on a systematic literature review comparing the nephrotoxic effects of iso- to low-osmolality contrast media. Only direct costs were considered; these were obtained from the official tariff manual. Incremental cost-effectiveness ratios, efficiency curves and acceptability curves were calculated. Univariate sensitivity analyses were performed for costs and effects, as well as probabilistic analyses. Zero and 3% discounts were applied to results. The cost-effectiveness threshold was equal to the per capita GDP per life-year gained. RESULTS: Alternatives with Iopamidol and Iodixanol are preferable to the others, because both reduce risk of contrast-induced nephropathy and are less costly. The incremental cost-effectiveness of the Iodixanol alternative compared to the Iopamidol alternative is US$ 14,660 per additional life year gained; this is more than twice the threshold. CONCLUSION: The low-osmolality contrast medium, Iopamidol, appears to be cost-effective when compared with Iohexol or other low-osmolality contrast media (Iopromide, Iobitridol, Iomeprol, Iopentol and Ioxilan) in contrast-induced nephropathy, high-risk outpatients. The choice of the iso-osmolality contrast medium, Iodixanol, depends on its cost per vial and on the willingness to pay.

Radiofrequency ablation for viable hepatocellular carcinoma around retained iodized oil after transcatheter arterial chemoembolization: usefulness of biplane fluoroscopy plus ultrasound guidance.

OBJECTIVE: To assess the technical feasibility and local efficacy of biplane fluoroscopy plus US-guided percutaneous radiofrequency ablation (RFA) for viable hepatocellular carcinoma (HCC) around retained iodized oil after transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Our prospective study was approved by our institutional review board and informed consent was obtained from all participating patients. For patients with viable HCC around retained iodized oil after TACE, biplane fluoroscopy plus US-guided RFA was performed. We evaluated the rate of technical success and major complications on a post-RFA CT examination and local tumor progression with a follow-up CT. RESULTS: Among 40 consecutive patients, 19 were excluded due to one of the following reasons: poorly visible HCC on fluoroscopy (n = 13), high risk location (n = 2), RFA performed under monoplane fluoroscopy and US guidance (n = 2), and poorly identifiable new HCCs on US (n = 2). The remaining 21 patients with 21 viable HCCs were included. The size of total tumors ranged from 1.4 to 5.0 cm (mean: 3.2 cm) in the longest diameter. Technical success was achieved for all 21 HCCs, and major complications were observed in none of the patients. During the follow-up period (mean, 20.3 months; range, 6.5-29.9 months), local tumor progression was found in two patients (2/21, 9.5%). Distant intrahepatic metastasis developed in 76.2% (16/21) of patients. CONCLUSION: When retained iodized oil around the tumor after TACE hampers the targeting of the viable tumor for RFA, biplane fluoroscopy plus US-guided RFA may be performed owing to its technical feasibility and effective treatment for viable HCCs.

Cost-effectiveness of iso- versus low-osmolality contrast media in outpatients with high risk of contrast medium-induced nephropathy / Costo-efectividad de medios de contraste isoosmolales e hiposmolales en pacientes con alto riesgo de nefropatía inducida por medio de contraste

Introduction. Contrast media can cause acute renal failure by direct toxic effects on the tubular cells and kidney ischemia. Diabetics and hospitalized patients have a greater risk of developing contrast-induced nephropathy than the general population. Objective. The cost effectiveness of iso and low-osmolality contrast media was assessed in high risk outpatients. Materials and methods. The analysis was based on a systematic literature review comparing the nephrotoxic effects of iso- to low-osmolality contrast media. Only direct costs were considered; these were obtained from the official tariff manual. Incremental cost-effectiveness ratios, efficiency curves and acceptability curves were calculated. Univariate sensitivity analyses were performed for costs and effects, as well as probabilistic analyses. Zero and 3% discounts were applied to results. The cost-effectiveness threshold was equal to the per capita GDP per life-year gained. Results. Alternatives with Iopamidol and Iodixanol are preferable to the others, because both reduce risk of contrast-induced nephropathy and are less costly. The incremental cost-effectiveness of the Iodixanol alternative compared to the Iopamidol alternative is US$ 14,660 per additional life year gained; this is more than twice the threshold. Conclusion. The low-osmolality contrast medium, Iopamidol, appears to be cost-effective when compared with Iohexol or other low-osmolality contrast media (Iopromide, Iobitridol, Iomeprol, Iopentol and Ioxilan) in contrast-induced nephropathy, high-risk outpatients. The choice of the iso-osmolality contrast medium, Iodixanol, depends on its cost per vial and on the willingness to pay.

Introducción. Los medios de contraste pueden provocar falla renal aguda por toxicidad directa sobre las células tubulares e isquemia medular renal. Los pacientes diabéticos y los hospitalizados presentan mayor riesgo de desarrollar nefropatía inducida por medios de contraste que la población general. Objetivo. Establecer el costo-efectividad de los medios de contraste isosmolales e hiposmolales en pacientes con alto riesgo. Materiales and métodos. El análisis se basó en una revisión sistemática de la literatura científica, comparando los efectos nefrotóxicos de los medios isosmolales e hipoosmolales. Se consideraron sólo los costos directos, obtenidos del manual tarifario. Se calcularon las tasas del incremento del costo-efectividad, las curvas de eficiencia y de aceptabilidad. Se hicieron análisis univariados de sensibilidad para costos y efectos, así como probabilísticos. Se aplicaron tasas de descuento de 0 y 3 % a los resultados. Se usó como umbral de costo-efectividad por año de vida ganado, el producto interno bruto per cápita. Resultados. Las alternativas con Iopamidol y Iodixanol dominan a las demás porque reducen el riesgo de nefropatía inducida por contraste a un menor costo. La razón del incremento del costo-efectividad del iodixanol comparado con el iopamidol es de US$ 14.660 por año de vida ganado que más que duplica el umbral. Conclusión. El medio de baja osmolalidad, iopamidol, parece ser costo-efectivo comparado con iohexol u otros medios hiposmolares (iopromide, iobitridol, iomeprol, iopentol y ioxilan), en pacientes con alto riesgo de nefropatía inducida por contraste. La elección del medio hiposmolar, depende de la disponibilidad a pagar o del costo por ampolleta.

Impact of short-duration administration of N-acetylcysteine, probucol and ascorbic acid on contrast-induced cytotoxicity.

BACKGROUND: The best pharmaceutical prevention of contrast-medium-induced nephropathy for emergency procedures remains unknown. The aim of this study was to examine the impact of short-duration antioxidant pretreatment on contrast-medium-induced cytotoxicity. METHODS: Human embryonic kidney cells were treated with three different contrast media: ionic ioxitalamate, non-ionic low-osmolar iopromide, and iso-osmolar iodixanol. The doses and durations of pretreatment with antioxidants were 2 mM/L N-acetylcysteine for 15 minutes, 40 µM/L probucol for 30 minutes, and 30 µM/L ascorbic acid for 30 minutes. A supplementary dose of 2 mM/L N-acetylcysteine was administered 12 hours after contrast medium treatment. Cell viability was determined by tetrazolium MTT assay. RESULTS: All three contrast media caused significant reduction of cell viability at 24 hours (p<0.001). In the groups receiving iopromide or iodixanol, N-acetylcysteine pretreatment significantly improved cell viability compared with no N-acetylcysteine pretreatment (p<0.001). In the group receiving ioxitalamate, N-acetylcysteine pretreatment followed by a supplementary dose of N-acetylcysteine at 12 hours rather than N-acetylcysteine pretreatment alone significantly improved cell viability compared with no N-acetylcysteine pretreatment (p=0.038). Probucol or ascorbic acid pretreatment was unable to reduce cell death caused by the three contrast media. CONCLUSIONS: Short-duration pretreatment with N-acetylcysteine significantly reduced contrast-medium-induced cytotoxicity. These findings provide new insight into the prevention of contrast-medium-induced nephropathy in clinical emergency scenarios.

Dynamic contrast-enhanced computed tomography imaging biomarkers correlated with immunohistochemistry for monitoring the effects of sorafenib on experimental prostate carcinomas.

OBJECTIVES: To investigate dynamic contrast-enhanced computed tomography (DCE-CT) for monitoring the effects of sorafenib on experimental prostate carcinomas in rats by quantitative assessments of tumor microcirculation parameters with immunohistochemical validation. MATERIAL AND METHODS: Prostate carcinoma allografts (MLLB-2) implanted subcutaneously in male Copenhagen rats (n=16) were imaged at baseline and after a 1-week treatment course of sorafenib using DCE-CT with iopromide (Ultravist 370, Bayer Pharma, Berlin, Germany) on a dual-source 128-slice CT (Somatom Definition FLASH, Siemens Healthcare, Forchheim, Germany). Scan parameters were as follows: detector width, 38.4 mm; contrast agent volume, 2 mL/kg bodyweight; injection rate, 0.5 mL/s; scan duration, 90 seconds; and temporal resolution, 0.5 seconds. The treatment group (n=8) received daily applications of sorafenib (10 mg/kg bodyweight) via gavage. Quantitative parameters of tumor microcirculation (plasma flow, mL/100 mL/min), endothelial permeability-surface area product (PS, mL/100 mL/min), and tumor vascularity (plasma volume, %) were calculated using a 2-compartment uptake model. DCE-CT parameters were correlated with immunohistochemical assessments of tumor vascularity (RECA-1), cell proliferation (Ki-67), and apoptosis (TUNEL). RESULTS: Sorafenib significantly (P < 0.05) suppressed tumor perfusion (25.1 ± 9.8 to 9.5 ± 6.0 mL/100 mL/min), tumor vascularity (15.6% ± 11.4% to 5.4% ± 2.1%), and PS (8.7 ± 4.5 to 2.7 ± 2.5 mL/100 mL/min) in prostate carcinomas during the treatment course. Immunohistochemistry revealed significantly lower tumor vascularity in the therapy group than in the control group (RECA-1; 181 ± 24 vs. 314 ± 47; P < 0.05). In sorafenib-treated tumors, significantly more apoptotic cells (TUNEL; 7132 ± 3141 vs. 3722 ± 1445; P < 0.05) and significantly less proliferating cells (Ki-67; 9628 ± 1.298 vs. 17,557 ± 1446; P < 0.05) were observed than those in the control group. DCE-CT tumor perfusion correlated significantly (P < 0.05) with tumor cell proliferation (Ki-67; r=0.55). DCE-CT tumor vascularity correlated significantly (P < 0.05) with immunohistochemical tumor cell apoptosis (TUNEL; r=-0.59) and tumor cell proliferation (Ki-67; r=0.68). DCE-CT endothelial PS correlated significantly (P < 0.05) with immunohistochemical tumor cell apoptosis (TUNEL; r=-0.6) and tumor vascularity (RECA-1; r=0.53). While performing corrections for multiple comparisons, we observed a significant correlation only between DCE-CT tumor vascularity (RECA-1) and tumor cell proliferation (Ki-67). CONCLUSION: Sorafenib significantly suppressed tumor perfusion, tumor vascularity, and PS quantified by DCE-CT in experimental prostate carcinomas in rats. These functional CT surrogate markers showed moderate correlations with antiangiogenic, antiproliferative, and proapoptotic effects observed by immunohistochemistry. DCE-CT may be applicable for the quantification of noninvasive imaging biomarkers of therapy response to antiangiogenic therapy.

Radiofrequency Ablation for Viable Hepatocellular Carcinoma around Retained Iodized Oil after Transcatheter Arterial Chemoembolization: Usefulness of Biplane Fluoroscopy Plus Ultrasound Guidance

OBJECTIVE: To assess the technical feasibility and local efficacy of biplane fluoroscopy plus US-guided percutaneous radiofrequency ablation (RFA) for viable hepatocellular carcinoma (HCC) around retained iodized oil after transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Our prospective study was approved by our institutional review board and informed consent was obtained from all participating patients. For patients with viable HCC around retained iodized oil after TACE, biplane fluoroscopy plus US-guided RFA was performed. We evaluated the rate of technical success and major complications on a post-RFA CT examination and local tumor progression with a follow-up CT. RESULTS: Among 40 consecutive patients, 19 were excluded due to one of the following reasons: poorly visible HCC on fluoroscopy (n = 13), high risk location (n = 2), RFA performed under monoplane fluoroscopy and US guidance (n = 2), and poorly identifiable new HCCs on US (n = 2). The remaining 21 patients with 21 viable HCCs were included. The size of total tumors ranged from 1.4 to 5.0 cm (mean: 3.2 cm) in the longest diameter. Technical success was achieved for all 21 HCCs, and major complications were observed in none of the patients. During the follow-up period (mean, 20.3 months; range, 6.5-29.9 months), local tumor progression was found in two patients (2/21, 9.5%). Distant intrahepatic metastasis developed in 76.2% (16/21) of patients. CONCLUSION: When retained iodized oil around the tumor after TACE hampers the targeting of the viable tumor for RFA, biplane fluoroscopy plus US-guided RFA may be performed owing to its technical feasibility and effective treatment for viable HCCs.

Vascular effects of paclitaxel following drug-eluting balloon angioplasty in a porcine coronary model: the importance of excipients.

AIMS: The vascular effects of drug- eluting balloon (DEB) deployment in the absence of coronary stents have not been characterised. This study evaluated potential vascular effects of paclitaxel-coated angioplasty balloons using different excipients in the absence of additional stents. METHODS AND RESULTS: A total 45 porcine arteries were treated with paclitaxel-coated DEBs using four different excipients (all 3.0 µg/mm2): A) iopromide (n=9), B) ATEC excipient (n=8), C) BTHC excipient (n=10), D) lecithine excipient (n=10). Uncoated bare angioplasty balloons served as controls (n=8). Histology, histomorphometry, and quantitative angiography analysis were performed 28 days following intervention. Tissue concentrations of paclitaxel were measured in selected animals using BTHC excipient (n=39 arteries) and reached maximum concentrations of 165 ng/mg 30 min after delivery in coronary target tissue. There were no differences in efficacy endpoints using histomorphology or quantitative angiography between groups. In contrast, however, treatment with DEBs using BTHC excipient or iopromide was associated with increased fibrin deposition and inflammation indicating delayed vascular healing. DEBs using lecithin excipient or uncoated angioplasty balloons did not induce any comparable vascular effects. CONCLUSIONS: Effective excipients are necessary to accomplish successful balloon facilitated paclitaxel delivery, which is associated with delayed vascular healing as a sign of successful drug transfer. The potential of DEBs to diminish restenosis following angioplasty may be insufficient in the absence of additional stents.

Evaluation of early imaging response after chemoembolization of hepatocellular carcinoma by phosphorus-31 magnetic resonance spectroscopy-initial experience.

PURPOSE: To evaluate the value of phosphorus-31 ((31)P) magnetic resonance (MR) spectroscopy in early monitoring and predicting the response of hepatocellular carcinoma (HCC) after chemoembolization. MATERIALS AND METHODS: The authors evaluated 17 HCC target tumors with (31)P MR spectroscopy before and after chemoembolization. Alterations of phosphorus metabolism were analyzed by the MR spectroscopy analysis package (SAGE 7.0; GE Medical Systems, Milwaukee, Wisconsin). Ratios of the peak areas of phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Pi) to the peak area of nucleoside triphosphates (NTP) or the total phosphorus content (TPC) were measured. The changes in these ratios after chemoembolization were calculated from baseline (before chemoembolization). The therapy effect was assessed by computed tomography (CT) or MR imaging 4 weeks after chemoembolization. The ability of phosphorus metabolism in monitoring therapy effect was evaluated by using receiver operating characteristic analysis. RESULTS: Decreases in the PDE/NTP ratio (Wilcoxon signed rank test, P = .024) and the PDE/TPC ratio (Wilcoxon signed rank test, P = .011) that occurred after treatment were the most remarkable changes secondary to chemoembolization. Of the 17 lesions evaluated quantitatively, at the follow-up examination done 4 weeks after chemoembolization, 12 lesions were responsive to chemoembolization, whereas 5 were not. In the responsive group, the PDE/TPC ratio (median 24.15% vs 13.15%; P = .008) was significantly decreased after chemoembolization, whereas the NTP/TPC ratio (median 37.35% vs 49.9%; P = .024) was significantly increased. In the nonresponsive group, phosphorus metabolism had no significant changes after treatment. Results from the receiver operating curve analysis showed that the threshold percentage change of the PDE/NTP (%PDE/NTP) value was -1.25% with 91.7% sensitivity and 100% specificity for identifying tumor response to chemoembolization, and the threshold percentage change of the NTP/TPC (%NTP/NTP) value was 15.3% with 75% sensitivity and 100% specificity. CONCLUSIONS: Phosphorus-31 MR spectroscopy is a promising technique for the noninvasive assessment of HCC response to chemoembolization. Future studies are necessary to confirm these preliminary results.