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.

Comparative long-term efficacy and safety of two paclitaxel-coated balloons with different coating strategies for the treatment of drug-eluting coronary stent restenosis.

BACKGROUND: We previously showed non-inferiority of a low-dose paclitaxel-coated balloon (PCB) with citrate excipient (Agent PCB) as compared to normal-dose iopromide excipient (SeQuent Please PCB) in terms of angiographic and clinical endpoints at 12 months. The long-term clinical efficacy and safety of Agent PCB is not defined. METHODS: 262 patients (323 DES-ISR lesions) were enrolled in this study and treated with either Agent PCB (125 patients, 151 lesions) in the ISAR-DESIRE 3a trial or with SeQuent Please PCB (137 patients, 172 lesions) in the setting of the randomized ISAR-DESIRE 3 trial with similar in- and exclusion criteria serving as historical control arm. The follow-up period was extended to 7 years. The efficacy and safety endpoints of this analysis were target-lesion revascularization (TLR), death, myocardial infarction (MI) and target lesion thrombosis (TLT) at 7 years. RESULTS: At 7 years, 206 patients (78.6%) were alive. The risks of TLR (hazard ratio [HR]: 1.29, 95% confidence interval [CI]: 0.87-1.90; p = 0.205), death (HR: 1.38, 95% CI: 0.82-2.35; p = 0.227), MI (HR: 1.10, 95% CI: 0.39-3.15; p = 0.852) and TLT (HR: 2.18, 95% CI: 0.20-24.10; p = 0.523) were comparable between Agent PCB and SeQuent PCB. Multivariate analysis showed comparable risks of TLR, death and MI between both PCB devices. CONCLUSIONS: In patients treated for DES-ISR by angioplasty with Agent PCB and SeQuent Please PCB, there was no statistically significant difference in TLR at 7 years. Randomized trials with standardized lesion preparation and long-term follow-up are warranted to further evaluate comparative efficacy of both devices. (ClinicalTrials. gov Identifier: NCT02367495).

Safety of non-ionic contrast media in CT examinations for out-patients: retrospective multicenter analysis of 473,482 patients.

OBJECTIVES: This study aimed to explore the incidence of and potential risk factors for adverse drug reactions (ADRs) after non-ionic iodinated contrast media (NICM) administration for CT exams in out-patient settings in China. MATERIALS AND METHODS: A total of 473,482 out-patients who underwent intravenous NICM between January 1st, 2017, and Dec 31st, 2021, were retrospectively enrolled from three institutions. The occurrence of ADRs and clinical information were recorded. Chi-square test, Poisson regression, and logistic regression analyses were used to evaluate potential ADR risk factors and correlation with demographics, season, and NICM type. RESULTS: Among the 473,482 patients (mean age 55.22 ± 14.85; 253,499 male) who received intravenous NICM, the overall ADR incidence was 0.110% (522 of 473,482), with 0.099% acute-related drug reactions (469 of 473,482) and 0.0004% serious ADRs (two of 473,482). Iopromide was associated with a higher risk of acute ADRs. Late ADRs were more frequently observed with iodixanol 320. Multi-level logistic regression of patients with acute ADRs and a control group (matched 1:1 for age, gender, NICM, prescriber department, and institution) showed that summer (adjusted OR = 1.579; p = 0.035) and autumn (adjusted OR = 1.925; p < 0.001) were risk factors of acute ADRs. However, underlying disease and scanned body area were not related to a higher ADR incidence. CONCLUSION: The use of NICM for out-patients is in general safe with a low ADR incidence. The type of contrast medium (iopromide) and the seasons (summer and autumn) were associated with a higher risk of acute ADRs. Late ADRs were more often observed with iodixanol. CLINICAL RELEVANCE STATEMENT: In comparison to in-patients, out-patients may be exposed to higher risk due to a lack of extensive risk screening, less nursing care, and higher throughput pressure. Safety data about NICM from a large population may complement guidelines and avoid ambiguity. KEY POINTS: • The incidence and risk factors for adverse events after using non-ionic iodinated contrast media are complex in out-patients. • Non-ionic iodinated contrast media are safe for out-patients and the overall incidence of adverse drug reactions was 0.110%. • There is a higher risk of acute adverse drug reactions in summer and autumn.

Discovery of a stilbenoid-flavanone hybrid as an antitumor Wnt/ß-catenin signaling pathway inhibitor.

A series of designed stilbenoid-flavanone hybrids featuring sp3-hybridized C2 and C3 atoms of C-ring was evaluated against colorectal cancers presented compounds 4, 17, and 20 as the most potential compounds among explored compounds. Evaluation of the anticancer activity spectrum of compounds 4, 17, and 20 against diverse solid tumors presented compounds 17 and 20 with interesting anticancer spectrum. The potencies of compounds 17 and 20 were assessed in comparison with FDA-approved anticancer drugs. Compound 17 was the, in general, the most potent showing low micromolar GI50 values that were more potent than the standard FDA-approved drugs against several solid tumors including colon, brain, skin, renal, prostate and breast tumors. Compound 17 was subjected for evaluation against normal cell lines and was subjected to a mechanism study in HCT116 colon cancer cells which presented it as an inhibitor of Wnt signaling pathway triggering G2/M cell cycle arrest though activation of p53-p21 pathway as well as intrinsic and extrinsic apoptotic death of colon cancer cells. Compound 17 might be a candidate for further development against diverse solid tumors including colon cancer.

Induction of breast cancer cell apoptosis by novel thiouracil-fused heterocyclic compounds through boosting of Bax/Bcl-2 ratio and DFT study.

Breast cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel pyrido[2,3-d]pyrimidine derivatives 3,4,(6a-c),(8a,b),9-20 were synthesized and characterized using a variety of spectrum analyses. The geometric and thermal parameters of the novel thiouracil derivatives 3,4,6a,(8a,b),11,12,17,18, 19 were measured using density functional theory (DFT) via DFT/B3LYP/6-31 + G(d,p) basis set. All synthesized compounds were evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) method using MCF-7 and MDA-MB-231 breast cancerous cells, compound 17 had the maximum anticancer activity against both breast cancerous cells, recording the lowest half-maximal inhibitory concentration (IC50) values (56.712 µg/mL for MCF-7 cells and 48.743 µg/mL for MDA-MB-231 cells). The results were confirmed in terms of the intrinsic mechanism of apoptosis, where compound 17 had the highest percentage in the case of both cancer cells and recorded Bax (Bcl-2 associated X)/Bcl-2 (B-cell lymphoma 2) ratio 17.5 and 96.667 for MCF-7 and MDA-MB-231 cells, while compound 19 came after 17 in the ability for induction of apoptosis, where the Bax/Bcl-2 ratio was 15.789 and 44.273 for both cancerous cells, respectively. Also, compound 11 recorded a high Bax/Bcl-2 ratio for both cells. The safety of the synthesized compounds was applied on normal WI-38 cells, showing minimum cytotoxic effect with undetectable IC50. Compounds 17, 11, and 19 recorded a significant increase of p53 upregulated modulator of apoptosis (PUMA) expression levels in the cancerous cells. The DFT method was also used to establish a connection between the experimentally determined values of the present investigated compounds and their predicted quantum chemical parameters. It was concluded that Compounds 17, 11, and 19 had anti-breast cancer potential through the induction of apoptotic Bax/Bcl-2 and PUMA expression levels.

Double low-dose computed tomography (CT) angiography of craniocervical arteries using a test bolus of diluted contrast medium and a personalized contrast protocol.

AIM: To prospectively assess the value of a test bolus of diluted contrast medium (CM) combined with a personalized contrast protocol in craniocervical computed tomography angiography (cc-CTA) with low radiation and CM doses. MATERIALS AND METHODS: Eighty-six consecutive subjects were divided into two groups at random (43 in each one): group A: 100/Sn140 kVp, filtered back-projection reconstruction, iopromide (370 mgI/ml) 50 ml; group B: 80/Sn140 kVp, iterative reconstruction, iodixanol (270 mgI/ml). In group B, the test bolus contained 27 ml of diluted CM, a personalized protocol with low-concentration CM was used for angiography, and the test bolus injection duration in angiography remained the same. Artery values over 200 Hounsfield units were considered significant. RESULTS: Image quality for all cases was found to be diagnostic. No significant differences were found in the arterial densities of the ascending aorta or basilar artery between the groups. The values of the common carotid artery, internal carotid artery, and middle cerebral artery in group B were significantly lower. The effective dose and average iodine uptake were significantly lower in group B. CONCLUSION: With double-low-dose cc-CTA, test bolus scanning based on diluted CM combined with a personalized contrast protocol can yield diagnostic-quality images and significantly reduce the radiation and CM doses.

Additional use of extrinsic warmer for intravenous CT contrast media and its impact on incidence of contrast extravasations and allergic like reactions: a prospective observational case control study.

AIMS: To prospectively determine whether extrinsic warming of the low-osmolality CT contrast media (Iohexol 350, Iodixanol 320, Iopromide 300, and Iopamidol 300) to 37°C prior to intravenous administration affects extravasation and allergic-like reaction rates. MATERIALS AND METHODS: This large scale prospective case control study of adverse events included all the patients between the age group of 15-80 years undergoing routine contrast-enhanced computed tomographic (CECT) examinations from April 2018 to March 2020 at our institute. Ex vivo experiments were also performed to demonstrate change in contrast viscosity and fluid dynamics in relation to temperature. RESULTS: A total of 24,379 CECTs were conducted during the study period. Extrinsic warming showed a significant decrease in extravasation rates for Iohexol 350 at flow rates <3.5 mL/sec (P=0.037). No significant difference was observed with Iopromide 300 (P=0.432). Overall, a significant decrease in allergic reactions and overall contrast-related reactions (excluding physiologic reactions) was noted (P<0.001), with Iohexol 350. However, no significant difference was found with Iopromide 300. The most common physiological reaction was a sense of warmth, more prevalent in the warmed group, aligning with ex-vivo experiments demonstrating decreased viscosity with contrast warming. CONCLUSIONS: Extrinsic warming of contrast helps reduce the incidence of allergic-like reactions and extravasations for Iohexol 350, but no significant difference was noted with Iopromide 300 even at low injection rates (<3.5 mL/sec).

Design, synthesis, and structure-activity relationship of novel RIPK2 inhibitors.

The NOD1/2 (nucleotide-binding oligomerization domain-containing protein 1/2) signaling pathways are involved in innate immune control and host defense. NOD dysfunction can result in a variety of autoimmune disorders. NOD-induced generation of inflammatory cytokines is mediated by receptor-interacting protein kinase 2 (RIPK2), which has been considered as a promising therapeutic target. Herein, we disclose the design, synthesis, and SAR study of a series of RIPK2 inhibitors. The lead compound 17 displayed a high affinity for RIPK2 (Kd = 5.9 nM) and was capable of inhibiting RIPK2 kinase function in an ADP-Glo assay. In vitro DMPK studies showed that compound 17 had good metabolic stability and no CYP inhibition. Compound 17 effectively suppressed inflammatory cytokine production in both cells and animal model.

Dynamic Perfusion Computed Tomography and Apparent Diffusion Coefficient as Potential Markers for Poorly Differentiated Pancreatic Adenocarcinoma.

INTRODUCTION: Tumor grade, one of the most important risk factors for survival, is routinely determined after examining the biopsy material or a surgically removed specimen. The aim of the study was to analyze computed tomography (CT) perfusion parameters and diffusion-weighted imaging apparent diffusion coefficient (ADC) values in pancreatic ductal adenocarcinoma (PDAC) and to establish the diagnostic value of these modalities determining the tumor grade. MATERIALS AND METHODS: A prospective clinical study included 56 subjects with PDAC. All the patients had a local perfusion assessment and ADC measurement of the tumor. For the prediction of poor tumor differentiation sensitivity, specificity, positive, and negative predictive values for each perfusion CT and ADC parameters based on cutoff values from ROC analysis were calculated. RESULTS: Mean transit time (MTT) and ADC values were found to be independent prognosticators for the presence of G3 PDAC. MTT and ADC at the cutoff of 17.37 s and 1.15 × 10-3 mm2/s, respectively, appeared to be significant parameters discriminating against the differentiation grade of PDAC. If both values exceeded the defined cutoff point, the estimated probability for the presence of G3 PDAC was 89.29%. CONCLUSION: The MTT parameter, calculated with the deconvolution method, and the ADC value may serve as effective independent prognosticators identifying poorly differentiated PDAC.

Transcatheter arterial embolization in abdominal blunt trauma with active mesenteric bleeding: case series and review of literature.

PURPOSE: To evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) in treating traumatic mesenteric injuries with active bleeding, to report the outcome in a case series, and to compare the results with the existing data. METHODS: All consecutive patients with active mesenteric bleeding due to blunt abdominal trauma referred to a level-one Trauma Center and treated by TAE were included; the related demographic and medical data were retrospectively reported. A literature review was conducted; all reported cases were collected and analysed together with our case series. A univariate analysis of risk factors for TAE failure, bowel necrosis, complication and length of stay was performed. RESULTS: Four consecutive patients were included. Technical success was 100%. One patient developed colon ischemia after the procedure and underwent surgical treatment; another presented transient mild renal failure and late respiratory failure. No 30-day mortality was reported. These results are consistent with those reported in literature. The analysis of our cases together with case collected from literature resulted in a case series of 25 patients. Univariate analysis showed colon as site of bleeding as a significant risk factor for bowel necrosis and older age as a significant risk factor for longer length of stay. TAE failure was not significantly associated neither with a higher complication rate nor with a higher length of stay. CONCLUSION: TAE is a safe and effective procedure to control mesenteric bleeding, thus should be considered, in selected cases and in appropriate setting, as an alternative to emergency surgery.

Combined rare anatomic variants: persistent primitive olfactory artery and azygos pericallosal artery.

The persisting primitive olfactory artery (PPOA) is a rare anatomic variation of the anterior cerebral artery (ACA), being encountered in less than 1% of cases. Different morphological types were reported previously. In type 3, only once reported previously, the PPOA gives off two branches, a nasal one which courses in the olfactory sulcus to supply the territory of the anterior ethmoidal artery, and the callosomarginal artery. It is reported here a combination of rare anatomic variants found in a 71-year-old male patient investigated by computed tomography angiography. A left PPOA left the A1 segment of the ACA and was classified as subtype 3b, as its branches were the nasal one and a frontal trunk, not the callosomarginal artery. That PPOA had a characteristic hairpin turn applied on the anterior fossa floor. The ACA continued as azygos pericallosal artery, which is also a rare finding. As the nasal branch of the PPOA and its hairpin turn is closely related to the anterior fossa floor, such variant should be carefully documented when combined approaches of the skull base are planned by rhinologists and neurosurgeons.

Anatomic variations of the superficial temporal artery.

The superficial temporal artery (STA) is a terminal branch of the external carotid artery. It is commonly described as coursing posterior to the mandibular condyle and over the posterior zygomatic root (PZR) and then dividing terminally into parietal and frontal branches. However, possible variations of the main trunk of the STA have seemingly been overlooked. This study retrospectively examined the archived head tomography angiograms of 43 patients to determine the morphology and topography of the STA prior to its terminal bifurcation. In 79% of patients, the STA topography related to the mandibular condyle was bilaterally symmetrical, either retrocondylar (65.1%) or laterocondylar (13.6%). The parietal branch was sometimes absent unilaterally (16.3%) or bilaterally (9.3%). In 2/43 cases, the frontal branch of the STA was unilaterally absent. When both terminal branches were present, the bifurcation was retrocondylar or immediately above the PZR when on the PZR, or the terminal division of the STA was high above the PZR. In 88.4% of the STAs, different patterns of kinking and coiling were documented, including retrocondylar kinks (27.9%), laterocondylar kinks (20.9%), kinks placed on the PZR (81.4%) and variably oriented suprazygomatic kinks (32.6%). Five of the 86 STAs were coiled, one retrocondylar, one laterocondylar, and three other placed on the PZR. Two cases showed unilateral pseudoaneurysms of the STA, one above the PZR and the other on the temporomandibular joint. The STA is surgically important; therefore, the number of anatomical studies of the STA should increase.

[Iopromide-Induced Encephalopathy: A Case Report and Literature Review].

A 42-year-old male was admitted for paroxysmal syncope for 10 + months, chest tightness for 20 + days and chest pain for 10 + days. The patient was diagnosed with hypertrophic cardiomyopathy. The patient did not have a history of hypertension or diabetes. Coronary angiography and left ventricular cardiac catheterization were done in order to examine the coronary artery and the pressure gradient of the left ventricular outflow tract. The cardiac catheterization was performed via a right radial artery approach and a total of 200 mL of 370 mg I/mL iopromide was injected. The patient developed contrast-induced encephalopathy following the cardiac catheterization procedure, displaying severe headache, cortical blindness and neuropsychiatric symptom as the main clinical manifestations. The patient was then given symptomatic and supportive treatment, including decreasing intracranial pressure, analgesics and sedatives, and the patient recovered.

Renal insufficiency following contrast media administration trial III: Urine flow rate-guided versus left-ventricular end-diastolic pressure-guided hydration in high-risk patients for contrast-induced acute kidney injury. Rationale and design.

BACKGROUND: Urine flow rate (UFR)-guided and left-ventricular end-diastolic pressure (LVEDP)-guided hydration regimens have been proposed to prevent contrast-induced acute kidney injury (CIAKI). The REnal Insufficiency Following Contrast MEDIA Administration triaL III (REMEDIAL III) is a randomized, multicenter, investigator-sponsored trial aiming to compare these two hydration strategies. METHODS: Patients at high risk for CIAKI (that is, those with estimated glomerular filtration rate ≤ 45 mL/min/1.73 m2 and/or with Mehran's score ≥11 and/or Gurm's score >7) will be enrolled. Patients will be randomly assigned to (a) LVEDP-guided hydration with normal saline (LVEDP-guided group) and (b) UFR-guided hydration carried out by the RenalGuard system (RenalGuard group). Seven-hundred patients (350 in each arm) will be enrolled. In the LVEDP-guided group the fluid infusion rate will be adjusted according to the LVEDP as follows: 5 mL kg-1 hr-1 for LVEDP ≤12 mmHg, 3 mL kg-1 hr-1 for LVEDP 13-18 mmHg, and 1.5 mL kg-1 hr-1 for LVEDP >18 mmHg. In the RenalGuard group hydration with normal saline plus low-dose of furosemide is controlled by the RenalGuard system, in order to reach and maintain a high (>300 mL/hr) UFR. In all cases, iobitridol (a low-osmolar, nonionic contrast agent) will be administered. RESULTS: The primary endpoint is the composite of CIAKI (i.e., serum creatinine increase ≥25% and/or ≥0.5 mg/dL from the baseline to 48 hr after contrast media exposure) and/or acute pulmonary edema. CONCLUSION: The REMEDIAL III will test the hypothesis that the UFR-guided hydration is superior to the LVEDP-guided hydration to prevent the composite of CIAKI and/or acute pulmonary edema.

Quantitative Analysis of Multiphase Contrast-Enhanced CT Images: A Pilot Study of Preoperative Prediction of Fat-Poor Angiomyolipoma and Renal Cell Carcinoma.

OBJECTIVE. The objective of our study was to preoperatively predict fat-poor angiomyolipoma (fp-AML) and renal cell carcinoma (RCC) by conducting quantitative analysis of contrast-enhanced CT images. MATERIALS AND METHODS. One hundred fifteen patients with a pathologic diagnosis of fp-AML or RCC from a single institution were randomly allocated into a train set (tumor size: mean ± SD, 4.50 ± 2.62 cm) and test set (tumor size: 4.32 ± 2.73 cm) after data augmentation. High-dimensional histogram-based features, texture-based features, and Laws features were first extracted from CT images and were then combined as different combinations sets to construct a logistic prediction model based on the least absolute shrinkage and selection operator procedure for the prediction of fp-AML and RCC. Prediction performances were assessed by classification accuracy, area under the ROC curve (AUC), positive predictive value, negative predictive value, true-positive rate, and false-positive rate (FPR). In addition, we also investigated the effects of different gray-scales of quantitative features on prediction performances. RESULTS. The following combination sets of features achieved satisfying performances in the test set: histogram-based features (mean AUC = 0.8492, mean classification accuracy = 91.01%); histogram-based features and texture-based features (mean AUC = 0.9244, mean classification accuracy = 91.81%); histogram-based features and Laws features (mean AUC = 0.8546, mean classification accuracy = 88.76%); and histogram-based features, texture-based features, and Laws features (mean AUC = 0.8925, mean classification accuracy = 90.36%). The different quantitative gray-scales did not have an obvious effect on prediction performances. CONCLUSION. The integration of histogram-based features with texture-based features and Laws features provided a potential biomarker for the preoperative diagnosis of fp-AML and RCC. The accurate diagnosis of benign or malignant renal masses would help to make the clinical decision for radical surgery or close follow-up.

Comparison of multimodal CT scan protocols used for decision-making on mechanical thrombectomy in acute ischemic stroke.

PURPOSE: Different CT-based protocols are being used in acute ischemic stroke. We aimed to assess the added value of delayed-phase CT angiography (CTA) and CT perfusion (CTP) to a basic protocol using non-contrast computerized tomography (NCCT) with arterial-phase CTA in patient selection for mechanical thrombectomy. METHODS: We retrospectively included consecutive acute ischemic stroke patients with a symptomatic intracranial arterial occlusion between January 2015 and November 2016 who underwent NCCT, arterial and delayed-phase CTA, and CTP. These imaging studies were grouped into five protocols: (1) NCCT and arterial-phase CTA; (2) NCCT, arterial-phase CTA, and CTP; (3) NCCT, arterial- and delayed-phase CTA; (4) NCCT, arterial- and delayed-phase CTA, and CTP; and (5) NCCT and delayed-phase CTA. Two interventional neuro-radiologists independently decided on mechanical thrombectomy for each patient based on the protocols. They reached consensus for discrepant decisions. We assessed the raters' confidence level, inter-rater agreement, and compared treatment decisions for the different protocols. RESULTS: We included 73 patients (44% male, mean age 74). The inter-rater agreement was substantial for protocols with three or more modalities (Ò¡ = 0.613-0.704) and moderate for two-modality protocols (Ò¡ = 0.506-0.529). The highest agreement and confidence level was achieved for the combination of NCCT, arterial-phase CTA, and CTP. Adding CTP to NCCT and arterial-phase CTA resulted in a 10% increase of recommendations for mechanical thrombectomy and adding delayed-phase CTA resulted in a 4% increase. These management changes did not reach statistical significance (p = 0.07; p = 0.25, respectively). CONCLUSION: Adding CTP and/or a delayed-phase CTA to NCCT with arterial-phase CTA improves the decision-maker's confidence level and creates a trend towards a lower threshold for mechanical thrombectomy.

MG53 protects against contrast-induced acute kidney injury by reducing cell membrane damage and apoptosis.

Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. This study was designed to investigate the effect of MG53 on CI-AKI and the underlying mechanism. A rat model of CI-AKI was established, and CI-AKI induced the translocation of MG53 from serum to injury sites on the renal proximal tubular (RPT) epithelia, as illustrated by immunoblot analysis and immunohistochemical staining. Moreover, pretreatment of rats with recombinant human MG53 protein (rhMG53, 2 mg/mL) alleviated iopromide-induced injury in the kidney, which was determined by measuring serum creatinine, blood urea nitrogen and renal histological changes. In vitro studies demonstrated that exposure of RPT cells to iopromide (20, 40, and 80 mg/mL) caused cell membrane injury and cell death, which were attenuated by rhMG53 (10 and 50 µg/mL). Mechanistically, MG53 translocated to the injury site on RPT cells and bound to phosphatidylserine to protect RPT cells from iopromide-induced injury. In conclusion, MG53 protects against CI-AKI through cell membrane repair and reducing cell apoptosis; therefore, rhMG53 might be a potential effective means to treat or prevent CI-AKI.

AdipoRon, an adiponectin receptor agonist, protects contrast-induced nephropathy by suppressing oxidative stress and inflammation via activation of the AMPK pathway.

BACKGROUND: Contrast-induced nephropathy (CIN), a complication caused by using contrast medium during diagnostic and interventional procedures, occurs frequently and lacks effective treatment. AdipoRon, the agonist of adiponectin receptors, has been shown to benefit many organs including the kidney. This study aimed to investigate the role of AdipoRon in treating CIN. METHODS: CIN model was established via infusing iopromide (1.8 g/kg) in Sprague-Dawley (SD) rats; NRK52E cells were treated with iopromide (5-50 µM). Renal function, renal histopathology, levels of lactate dehydrogenase (LDH) release, cell vitality, oxidative stress and inflammatory markers were measured to evaluate the protective effects of AdipoRon. The level of pAMPK/AMPK was determined by western blot. RESULTS: AdipoRon (50 mg/kg) significantly reversed serum creatinine, blood urea nitrogen, creatinine clearance and urinary kidney injury molecule-1 levels induced by iopromide in SD rats. Besides, it decreased the renal injury score and apoptosis of renal cells. AdipoRon also reversed the changes of antioxidant markers, pro-oxidant and inflammatory markers induced by iopromide. Moreover, the in vitro studies showed that AdipoRon decreased LDH release and increased cell vitality in NRK52E cells treated with iopromide. Then, we demonstrated that the protection of AdipoRon was accompanied by augmented AMPK phosphorylation. Both in vivo and in vitro studies demonstrated that compound c, an AMPK inhibitor, reversed the AdipoRon-mediated improvement in the CIN model. CONCLUSION: Our data indicate that AdipoRon protects against the CIN by suppressing oxidative stress and inflammation via activating the AMPK pathway, showing that AdipoRon might be a potential candidate for the prevention and therapy of CIN.

Evaluation of diagnostic accuracy of intracranial aneurysm detection using medical-grade versus commercial consumer-grade displays and different image reconstructions against the background of process optimization for telemedicine.

BACKGROUND: Process optimization in computed tomography (CT) and telemedicine. PURPOSE: To compare image quality and objective diagnostic accuracy of medical-grade and consumer-grade digital displays/computer terminals for detection of intracranial aneurysms. MATERIAL AND METHODS: Four radiologists with different levels of experience retrospectively read a total of 60 patients including 30 cases of proven therapy-naïve intracranial aneurysm detectable on a medical-grade grayscale calibrated display. They had 5 min per case reading the first 20 datasets using only axial slices, the next 20 patients using axial slices and multiplanar reconstructions (MPRs), and the last 20 patients using axial slices, MPRs, and maximum intensity projections (MIPs). Three months after the first reading session on a medical-grade display, they read all datasets again under the same standardized conditions but on a consumer-grade display. Diagnostic performance, subjective diagnostic confidence, and reading speed were analyzed and compared. Readers rated image quality on a five-point Likert scale. RESULTS: Diagnostic accuracy did not differ significantly with areas under the curve of 0.717-0.809 for all readers on both display devices. Sensitivity and specificity did not increase significantly when adding MPRs and/or MIPs. Reading speed was similar with both devices. There were no significant differences in subjective image quality scores, and overall inter-reader variability of all subjective parameters correlated positively between the two devices (P <0.001-0.011). CONCLUSION: Diagnostic accuracy and readers' diagnostic confidence in detecting and ruling out intracranial aneurysm were similar on commercial-grade and medical-grade displays. Additional reconstructions did not increase sensitivity/specificity or reduce the time needed for diagnosis.

Flat-panel CT arthrography for cartilage defect detection in the ankle joint: first results in vivo.

OBJECTIVES: The purpose of this study was to compare the diagnostic performance of flat-panel computed tomography (FPCT) arthrography for cartilage defect detection in the ankle joint to direct magnetic resonance (MR) arthrography using multidetector computed tomography (MDCT) arthrography as the reference standard. METHODS: Twenty-seven patients with specific suspicion of articular cartilage lesion underwent ankle arthrography with injection of a mixture of diluted gadolinium and iobitridol and were examined consecutively with the use of FPCT, MDCT, and 1.5 T MR imaging. FPCT, MDCT, and MR arthrography examinations were blinded and randomly evaluated by two musculoskeletal radiologists in consensus. In each ankle, eight articular cartilage areas were assessed separately: medial talar surface, medial talar trochlea, lateral talar trochlea, lateral talar surface, tibial malleolus, medial tibial plafond, lateral tibial plafond, and fibular malleolus. Findings at FPCT and MR were compared with MDCT assessments in 216 cartilage areas. RESULTS: For the detection of cartilage defects, FPCT demonstrated a sensitivity of 97%, specificity of 95%, and accuracy of 96%; and MR arthrography showed a sensitivity of 69%, specificity of 94%, and accuracy of 87%. FPCT and MR arthrography presented almost perfect agreement (κ = 0.87) and moderate agreement (κ = 0.60), respectively, with MDCT arthrography. Mean diagnostic confidence was higher for FPCT (2.9/3) than for MR (2.3/3) and MDCT (2.7/3) arthrography. CONCLUSIONS: FPCT demonstrated better accuracy than did 1.5 T MR arthrography for cartilage defect detection in the ankle joint. Therefore, FPCT should be considered in patients scheduled for dedicated imaging of ankle articular cartilage.