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.

Iohexol is an intestinal permeability marker in broilers under coccidiosis challenge.

Intestinal integrity losses have been identified as a main driver for poor performance in broilers. The oral administration of markers such as iohexol is a major asset for measuring intestinal permeability (IP) alterations. The aim of the current study was to evaluate oral iohexol administration and serum levels as a quantitative measure for IP in Ross 308 broilers and to identify possible associations with histologic measurements. A total of 40, day-old broiler chickens were randomly divided into 4 groups of 10 broilers and a coccidiosis model was used to induce IP. Three challenge groups received a mixture of different field strains and concentrations of Eimeria acervulina and Eimeria maxima at d 16, and 1 group operated as an uninfected control group. On d 20, 5 birds per group were orally administered the permeability marker iohexol at a dose of 64.7 mg/kg body weight and blood was taken 60 min after the oral gavage. On d 21 these 5 birds per group were euthanized. On d 21, 5 other birds per group were given iohexol where after blood was taken. These birds were euthanized on d 22. During necropsy, birds were scored for coccidiosis lesions and a duodenal segment was taken for histology. The Eimeria challenge had a significant impact on the villus length, crypt depth, villus-to-crypt ratio and CD3+ T-lymphocytes area percentage. Challenged birds had a significant higher concentration of serum iohexol on both sampling days, as compared to the uninfected controls. A significant correlation could be found between the serum iohexol concentration and the histologic parameters (villus length, crypt depth and villus-to-crypt ratio) on the first sampling day. This suggests that iohexol may be used as a gut permeability marker in broilers under Eimeria challenge.

A proof of principle study investigating the effects of supplemental concentrated brewer's yeast on markers of gut permeability, inflammation, and fecal metabolites in healthy non-challenged adult sled dogs.

Yeast-derived ß-glucans impact immunity, though their effects on gut permeability and inflammation are less understood. Most research has investigated other components of the yeast cell wall, such as the prebiotic mannan- and fructo-oligosaccharides. The objective of this study was to assess the effects of feeding a concentrated yeast product on markers of inflammation (serum amyloid A [SAA] and haptoglobin [Hp]) and oxidative status (malondialdehyde [MDA]), fecal products of fermentation, and gut permeability. Nineteen privately owned domestic Siberian huskies, and one Alaskan husky (9 females: 5 intact, 4 spayed; 11 males: 3 intact, 8 neutered), with an average age of 4.8 ± 2.6 yr and body weight (BW) of 25.6 ± 4.1 kg, were used in this study. Dogs were blocked and randomly allocated to one of two diet groups. Ten dogs received a dry extruded diet. The other 10 received the same diet top dressed with yeast for a daily ß-glucan dose of 7 mg/kg BW for 10 wk. Fecal collection, for evaluation of fecal metabolites, and scoring occurred weekly. Gut permeability was assessed using the chromium-labeled ethylenediamine tetra-acetic acid (Cr-EDTA) and iohexol markers prior to the initiation of dietary treatment and after 10 wk of treatment. Blood samples were collected premarker administration and 0.5, 1, 2, 3, 4, 5, and 6 h postadministration. Fasting concentrations of SAA, Hp, and MDA were measured on weeks -1, 2, 4, and 8. Incremental area under the curve (I-AUC) was calculated for serum iohexol and Cr-EDTA concentrations. All data were analyzed using PROC GLIMMIX of SAS with dog as random effect, and week as fixed effect and repeated measure. Dogs receiving treatment tended to have decreased I-AUC of Iohexol (P = 0.10) and Cr-EDTA (P = 0.06) between baseline and cessation of treatment compared to the change over time in I-AUC for control (Ctl) dogs. Treatment dogs had lower Hp concentrations (P ≤ 0.05) than Ctl. There were no differences between treatments for SAA and MDA concentrations (P > 0.05). Fecal arabinose concentrations were greater in treatment (Trt) dogs (P ≤ 0.05) compared to Ctl, though no other fecal metabolites were affected by treatment. There was no difference in the relative frequency of defecations scored at any fecal score between Trt and Ctl dogs, and mean score did not differ between groups (P > 0.10). These data suggest that concentrated brewer's yeast may have the potential to reduce gut permeability without impacting inflammatory status and markers of health in adult dogs.

This study evaluated the effects of concentrated brewer's yeast on gut health in dogs. Nineteen Siberian Huskies and one Alaskan husky were blocked and randomly allocated to one of two groups. Treatment dogs received a yeast supplement for 10 wk, while control dogs received no supplement. Dogs were administered two markers to assess intestinal permeability prior to start of treatment and following 10 wk of treatment. Blood samples were collected and analyzed for markers of inflammatory status (serum amyloid A [SAA] and Haptoglobin [Hp]) and oxidative status (serum malondialdehyde [MDA]). Fecal samples were collected weekly to assess fecal score as well as fecal metabolite concentrations. Intestinal permeability was reduced in treatment dogs following treatment, and no change was observed in the control group. Treatment dogs had lower Hp concentrations than control (Ctl), but there were no differences between treatments for SAA and MDA. Fecal arabinose concentrations were significantly greater in the treatment group when compared to control. There were no differences in the relative frequency of defecations scored at any fecal score between treatment and Ctl dogs, nor did mean score differ between the groups. This study suggests that concentrated brewer's yeast may reduce gut permeability and inflammation without detrimentally impacting markers of health in adult dogs.

Noninvasive Staging of Liver Fibrosis Using 5-Minute Delayed Dual-Energy CT: Comparison with US Elastography and Correlation with Histologic Findings.

Background Normalized iodine concentration (NIC) (ratio of iodine concentration of liver to that of aorta) of liver at delayed dual-energy CT (DECT) may reflect the amount of fibrosis based on the extent of iodine uptake. Purpose To stage liver fibrosis by using 5-minute delayed DECT and compare findings with those of transient elastography (TE), shear-wave elastography (SWE), and histologic examination. Materials and Methods This prospective study included patients with chronic liver disease who were scheduled to undergo multiphase abdominal CT and liver biopsy from January 2017 to September 2018. Fifty individuals being screened as renal donors comprised the control group. Study participants underwent TE, SWE, multiphasic DECT (including 5-minute delayed dual-energy scanning), and liver biopsy. Multiphasic DECT and SWE were performed in the control group. The NIC of the right lobe of the liver (RNIC) was compared with liver stiffness (LS) as measured with TE and SWE and with the METAVIR fibrosis stage (ranging from F0 to F4). Diagnostic performance was assessed by using areas under the receiver operating characteristic curve (AUCs). Results A total of 107 participants (mean age, 35 years ± 12 [standard deviation]; 57 men) and 50 control subjects (mean age, 47 years ± 11; 29 women) were evaluated. The RNIC showed strong correlation with METAVIR stage (Spearman ρ = 0.81, P < .001). The AUC for RNIC with each METAVIR stage ranged between 0.86 (95% CI: 0.76, 0.97) and 0.96 (95% CI: 0.92, 0.99). The cut-off value of RNIC was 0.24 (sensitivity: 85% [86 of 101 participants; 95% CI: 77%, 91%]; specificity: 83% [84 of 101 participants; 95% CI: 42%, 98%]) for stage F1 fibrosis and 0.29 (sensitivity: 84% [67 of 80 participants; 95% CI: 74%, 90%]; specificity: 81% [65 of 80 participants; 95% CI: 63%, 92%]) for stage F2 fibrosis. RNIC correlated well with LS as measured with TE and SWE (Spearman ρ = 0.60 and 0.64, respectively; P < .001). Conclusion Normalized iodine concentration of liver at 5-minute delayed dual-energy CT showed strong correlation with the histologic stages of liver fibrosis and good diagnostic performance in estimating liver fibrosis. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Chandarana and Shanbhogue in this issue.

Optimization of the isolation procedure and culturing conditions for hepatic stellate cells obtained from mouse.

Liver fibrosis (LF) mortality rate is approximately 2 million per year. Irrespective of the etiology of LF, a key element in its development is the transition of hepatic stellate cells (HSCs) from a quiescent phenotype to a myofibroblast-like cell with the production of fibrotic proteins. It is necessary to define optimal isolation and culturing conditions for good HSCs yield and proper phenotype preservation for studying the activation of HSCs in vitro. In the present study, the optimal conditions of HSC isolation and culture were examined to maintain the HSC's undifferentiated phenotype. HSCs were isolated from Balb/c mice liver using Nycodenz, 8, 9.6, and 11%. The efficiency of the isolation procedure was evaluated by cell counting and purity determination by flow cytometry. Quiescent HSCs were cultured in test media supplemented with different combinations of fetal bovine serum (FBS), glutamine (GLN), vitamin A (vitA), insulin, and glucose. The cells were assessed at days 3 and 7 of culture by evaluating the morphology, proliferation using cell counting kit-8, lipid storage using Oil Red O (ORO) staining, expression of a-smooth muscle actin, collagen I, and lecithin-retinol acyltransferase by qRT-PCR and immunocytochemistry (ICC). The results showed that Nycodenz, at 9.6%, yielded the best purity and quantity of HSCs. Maintenance of HSC undifferentiated phenotype was achieved optimizing culturing conditions (serum-free Dulbecco's Modified Eagle's Medium (DMEM) supplemented with glucose (100 mg/dl), GLN (0.5 mM), vitA (100 µM), and insulin (50 ng/ml)) with a certain degree of proliferation allowing their perpetuation in culture. In conclusion, we have defined optimal conditions for HSCs isolation and culture.

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.

Bismuth chelate as a contrast agent for X-ray computed tomography.

BACKGROUNDS: Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming. METHODS: In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. RESULTS: The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. CONCLUSIONS: This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.

Effects of a single-bolus bupivacaine injection into the coccygeal spinal canal of rabbits.

It has been reported that drugs intended for epidural administration through the lumbosacral junction are accidentally administered into the subarachnoid space frequently in rabbits. Therefore, we evaluated the epidural single-bolus injection technique for the administration of bupivacaine into the coccygeal spinal canal of rabbits. After epidural distribution was confirmed by the injection of iohexol into the coccygeal spinal canal, 0.3 ml/kg 0.5% bupivacaine or 0.3 ml/kg normal saline was injected via the same needle. After the first attempt of iohexol injection, although the contrast was found in the epidural space in all rabbits, the additional contrast was also found in blood vessel in 3 rabbits and in muscular layer in 1 rabbit. Subarachnoid distribution was not observed in any of the rabbits. The time taken to regain normal anal reflex, movement of the hind limbs during walking, conscious proprioception of the hind limbs, and pain sensation of the tail and left hind limb, following coccygeal spinal canal injection, were significantly longer in the bupivacaine group than in the normal saline group. These findings indicated that coccygeal epidural injection of bupivacaine in rabbits may provide anesthesia for the hind limbs, perineum, and tail, but inadvertent vascular entry of the epidural drug may occur.

Injectable Ovalbumin-Based Composite Implant for Photothermal Tumor Therapy.

Polymeric hydrogels with three-dimensional network structures have found tremendous applications in biomedicine. Herein, we report the synthesis of a multifunctional implant based on ovalbumin (OVA) as a carrier capable of synergistically delivering a photothermal transducing agent (polydopamine, PDA) to tumors. The formation of PDA was achieved by utilizing the basicity of OVA, whereas the formation of the hydrogel implant was achieved through the in vitro/in vivo near-infrared (NIR) laser-induced hyperthermia of PDA. The as-prepared PDA@OVA implant exhibits high photothermal conversion efficiency (38.7 %). Once implanted in vivo, the OVA-based implant shows great versatility in the treatment of malignant tumors. Furthermore, a chemotherapeutic (doxorubicin, DOX) and a contrast agent (iohexol), dispersed in the OVA solution in advance, can also be firmly entrapped in the hydrogel along with the hydrogel formation. It is anticipated that the multifunctional OVA-based implant, not showing any obvious toxicity to healthy tissue, could be a promising system for synergistic cancer treatment.

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.

Outcomes of a low-osmolar water-soluble contrast pathway in small bowel obstruction.

BACKGROUND: Adhesive small-bowel obstruction (SBO) is a common surgical condition accounting for a significant proportion of acute surgical admissions and surgeries. The implementation of a high-osmolar water-soluble contrast challenge has repeatedly been shown to reduce hospital length of stay and possibly the need for surgery in SBO patients. The effect of low-osmolar water-soluble contrast challenge however, is unclear. The aim of this study is to evaluate the outcomes of an SBO pathway including a low-osmolar water-soluble contrast challenge. METHODS: A prospective cohort of patients admitted for SBO were placed on an evidence-based SBO pathway including low-osmolar water-soluble contrast between January 2017 and October 2018 and were compared with a historical cohort of patients prior to the implementation of the pathway from September 2013 through December 2014. The primary outcome was length of stay less than 4 days with a secondary outcome of failure of nonoperative management. RESULTS: There were 140 patients enrolled in the SBO pathway during the study period and 101 historic controls. The SBO pathway was independently associated with a length of stay less than 4 days (odds ratio, 1.76; 95% confidence interval, 1.03-3.00). Median length of stay for patients that were successfully managed nonoperatively was lower in the SBO pathway cohort compared with controls (3 days vs. 4 days, p = 0.04). Rates of readmission, surgery, and bowel resection were not significantly different between the two cohorts. CONCLUSION: Implementation of an SBO pathway using a low-osmolarity contrast is associated with decreased hospital length of stay. Rates of readmission, surgery, and need for bowel resection for those undergoing surgery were unchanged. An SBO pathway utilizing low-osmolarity water-soluble contrast is safe and effective in reducing length of stay in the nonoperative management of adhesive small-bowel obstructions. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Evaluation of Renal Pathophysiological Processes Induced by an Iodinated Contrast Agent in a Diabetic Rabbit Model Using Intravoxel Incoherent Motion and Blood Oxygenation Level-Dependent Magnetic Resonance Imaging

OBJECTIVE: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model. MATERIALS AND METHODS: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were calculated. RESULTS: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels. CONCLUSION: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.

Dual-Energy CT Iodine Mapping and 40-keV Monoenergetic Applications in the Diagnosis of Acute Bowel Ischemia.

OBJECTIVE: Sensitivity of CT of the abdomen for detection of acute bowel ischemia (ABI) can be as low as 60%. In this study, we assessed the diagnostic performance of iodine-map and monoenergetic (40-keV) images in patients with suspected ABI. MATERIALS AND METHODS: This retrospective study included 60 consecutive patients with suspected ABI who underwent a standardized imaging protocol dual-source dual-energy CT (DECT) over a 26-month period. Clinical and operative outcomes were recorded as the reference standard. Two abdominal radiologists who were unaware of clinical and surgical information independently assessed conventional CT images for ABI. After a time interval designed to reduce recall, readers reassessed conventional images with supplementary iodine-map and 40-keV postprocessed images. Quantitative ROI analysis was also performed. RESULTS: ABI was observed in 11 patients. For reader A, sensitivity was 63.6% (95% CI, 30.8-89.1%) when interpreting conventional images alone. Sensitivity for detection of ABI increased to 81.8% (95% CI, 48.2-97.7%) and 100% (95% CI, 71.5-100%) when iodine-map and 40-keV images were assessed, respectively. For reader B, no change in sensitivity was seen with either technique, but the number of false-positives were reduced with supplementary iodine-map and 40-keV postprocessed images. Interobserver agreement was fair with conventional images (κ = 0.29) but improved to moderate (κ = 0.45) and substantial (κ = 0.63) with iodine-map and 40-keV images, respectively. Quantitative assessment found significant differences in iodine uptake (1.01 ± 0.55 mg/mL vs 3.04 ± 1.19 mg/mL) and mean attenuation (75.2 ± 38.4 HU vs 163.5 ± 48.9 HU) between nonischemic and ischemic segments, respectively. CONCLUSION: Iodine-map and 40-keV monoenergetic images increase conspicuity of ABI, resulting in improved diagnostic accuracy compared with review of conventional CT images alone.

Applicability of current NCCN Guidelines for pancreatic adenocarcinoma resectability: analysis and pitfalls.

PURPOSE: To test the applicability of National Comprehensive Cancer Network (NCCN v 3.2017) resectability criteria for pancreatic ductal adenocarcinoma (PDAC) in clinical practice, at a high-volume tertiary referral center. MATERIALS AND METHODS: 102 consecutive patients (53 female; mean age 66.2 years, range 34-90 years) with biopsy proven, non-metastatic PDAC were evaluated by our multidisciplinary pancreatic cancer program between July 2013 and February 2016. Retrospective review of staging pancreatic CT angiography was performed, and radiographic features were categorized as conforming to or non-conforming to existing v 3.2017 definitions. RESULTS: Among 102 patients, 10 (10%) had CTA evidence of vascular involvement that did not conform to existing NCCN Guidelines. Six new scenarios of vascular involvement were identified. The remaining 92 patients presented with resectable (n = 20 [22%]), borderline resectable (n = 42 [45.6%]), or unresectable (n = 30 [33%]) PDAC. Approximately half (n = 21 [51%]) of borderline resectable patients' tumors demonstrated isolated venous involvement, whereas 39% had both arterial and venous involvement. A minority (11%) demonstrated only major arterial involvement. Assignment to unresectable status reflected both arterial and venous involvement (11, 37%), arterial involvement only (10, 33%) patients, and unreconstructible venous involvement in 9 (30%). CONCLUSION: In our experience, current NCCN resectability guidelines for PDAC do not accurately classify vascular involvement identified in approximately 10% of patients. Revision of the current guidelines could be helpful to clinical practice.

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.

Ascorbic acid ameliorates renal injury in a murine model of contrast-induced nephropathy.

BACKGROUND: Contrast induced nephropathy (CIN) is the commonest cause of iatrogenic renal injury and its incidence has increased with the advent of complex endovascular procedures. Evidence suggests that ascorbic acid (AA) has a nephroprotective effect in percutaneous coronary interventions when contrast media are used. A variety of biomarkers (NGAL, NGAL:creatinine, mononuclear cell infiltration, apoptosis and RBP-4) in both the urine and kidney were assayed using a mouse model of CIN in order to determine whether AA can reduce the incidence and/or severity of renal injury. METHODS: Twenty-four BALB/c mice were divided into 4 groups. Three groups were exposed to high doses of contrast media (omnipaque) in a well-established model of CIN, and then treated with low or high dose AA or placebo (saline). CIN severity was determined by measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL):creatinine at specific time intervals. Histological analysis was performed to determine the level of mononuclear inflammatory infiltration as well as immunohistochemistry to determine apoptosis in the glomeruli by staining for activated caspase-3 and DNA nicking (TUNEL assays). Reverse transcriptase PCR (rtPCR) of mRNA transcripts prepared from mRNA extracted from mouse kidneys was also performed for both lipocalin-2 (Lcn2) encoding NGAL and retinol binding protein-6 (RBP4) genes. NGAL protein expression was also confirmed by ELISA analysis of kidney lysates. RESULTS: Urinary NGAL:creatinine ratio was significantly lower at 48 h with a 44% and 62% (204.3µg/mmol versus 533.6µg/mmol, p = 0.049) reduction in the low and high dose AA groups, respectively. The reduced urinary NGAL:creatinine ratio remained low throughout the time period assessed (up to 96 h) in the high dose AA group. In support of the urinary analysis ELISA analysis of NGAL in kidney lysates also showed a 57% reduction (12,576 ng/ml versus 29,393 ng/ml) reduction in the low dose AA group. Immunohistochemistry for apoptosis demonstrated decreased TUNEL and caspase-3 expression in both low and high dose AA groups. CONCLUSIONS: Ascorbic acid reduced the frequency and severity of renal injury in this murine model of CIN. Further work is required to establish whether AA can reduce the incidence of CIN in humans undergoing endovascular procedures.

Efficacy of oral supplemental hydration for the prevention of contrast-induced nephropathy in rats.

PURPOSE: To compare oral rehydration solution (ORS) with saline infusion for preventing contrast-induced nephropathy (CIN) in a rat model. MATERIALS AND METHODS: Adult male Sprague-Dawley rats (310-360 g) received intravenous indomethacin (10 mg/kg), N G-nitro-L-arginine methyl ester (10 mg/kg), and iohexol (10 mL/kg) to induce acute contrast-induced renal injury (CIN group); control rats received saline only. For hydration, rats received either continuous infusion (20 mL/kg/h) of saline or three oral doses (20 mL/kg each) of ORS. Acute renal injury was evaluated by assaying urine collected for 24 h beginning 2 h before the contrast injection, evaluating blood taken 22 h after the contrast injection, and examining the kidneys histopathologically. RESULTS: Hydration with saline prevented only the contrast-induced increase in plasma creatinine, whereas ORS prevented deleterious changes in plasma creatinine, blood urea nitrogen, and creatinine clearance as well as in urinary protein, albumin, and N-acetyl-D-glucosaminidase concentrations. Histopathologic changes noted in the CIN group were diminished in both saline and ORS groups. CONCLUSION: Both intravenous saline administration and oral hydration with ORS decreased the severity of CIN. Hydration with ORS was comparable to intravenous saline infusion in preventing CIN-associated abnormalities.

Carbon Dioxide as Contrast Medium to Guide Endovascular Aortic Aneurysm Repair.

BACKGROUND: Iodine contrast medium (ICM) is considered to be gold standard in endovascular procedures, but its nephrotoxicity and hypersensitivity limit the widespread use. Carbon dioxide (CO2) is considered as an alternative for endovascular procedures in patients with contraindication to ICM. However, no studies have compared the outcomes of endovascular aneurysm repair (EVAR) performed with ICM or CO2 among patients with no contraindication to ICM. METHODS: From May 2012 to April 2014, 36 patients with abdominal aortic aneurysms underwent EVAR in a prospective, randomized, and controlled study. Patients were randomized into 2 groups, CO2 or ICM group. RESULTS: We were able to perform the proposed procedures in all patients in this study. There were no conversions to open surgery and no CO2-related complications. Endovascular material costs, duration of surgery, and time of fluoroscopy were similar between groups, and the cost of the contrast media was smaller in the CO2 group than in the ICM group. Among CO2 group procedures, 62.5% of the patients needed ICM complementary use. CONCLUSIONS: The use of CO2 as a contrast medium for EVAR is an alternative in patients with no restriction for ICM, with similar outcomes when compared to ICM, regarding duration of surgery, duration of fluoroscopy, and endovascular material costs. Using CO2, there were no changes in creatinine clearance and no risk of hypersensitivity reactions; moreover, there was a reduction in contrast-related costs for EVAR procedures. However, in our study, additional use of ICM to visualize the internal iliac artery was needed in most procedures.

Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats.

Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals. Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI. O-linked ß-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear. Increasing evidence suggests that O-GlcNAc levels are increased in response to stress and that acute augmentation of this reaction is cytoprotective. However, the underlying mechanisms by which augmented OGlcNAc signaling provides renoprotection against contrast media insults is still unknown. Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling. We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h. The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress. Furthermore, this renoprotection was blocked by treatment with alloxan, an O-GlcNAc transferase inhibitor. Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3ß, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3. Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway. We further identified O-GlcNAcylated Akt through immunoprecipitation and western blot. We confirmed that Akt was modified by O-GlcNAcylation, and glucosamine pretreatment increased the O-GlcNAcylation of Akt. Collectively, the results demonstrate that glucosamine induces renoprotection against CI-AKI through augmented O-GlcNAc and activation of PI3K/Akt signaling, making it a promising strategy for preventing CI-AKI.