Monitoring Pharmaceuticals and Personal Care Products in Healthcare Effluent Wastewater Samples and the Effectiveness of Drug Removal in Wastewater Treatment Plants Using the UHPLC-MS/MS Method.

A multi-residue UHPLC-MS/MS analytical method, previously developed for monitoring 52 pharmaceuticals in drinking water, was used to analyse these pharmaceuticals in wastewater originating from healthcare facilities in the Czech Republic. Furthermore, the methodology was expanded to include the evaluation of the effectiveness of drug removal in Czech wastewater treatment plants (WWTPs). Of the 18 wastewater samples analysed by the validated UHPLC-MS/MS, each sample contained at least one quantifiable analyte. This study reveals the prevalence of several different drugs; mean concentrations of 702 µg L-1 of iomeprol, 48.8 µg L-1 of iopromide, 29.9 µg L-1 of gabapentin, 42.0 µg L-1 of caffeine and 82.5 µg L-1 of paracetamol were present. An analysis of 20 samples from ten WWTPs revealed different removal efficiencies for different analytes. Paracetamol was present in the inflow samples of all ten WWTPs and its removal efficiency was 100%. Analytes such as caffeine, ketoprofen, naproxen or atenolol showed high removal efficiencies exceeding 80%. On the other hand, pharmaceuticals like furosemide, metoprolol, iomeprol, zolpidem and tramadol showed lower removal efficiencies. Four pharmaceuticals exhibited higher concentrations in WWTP effluents than in the influents, resulting in negative removal efficiencies: warfarin at -9.5%, indomethacin at -53%, trimethoprim at -54% and metronidazole at -110%. These comprehensive findings contribute valuable insights to the pharmaceutical landscape of wastewater from healthcare facilities and the varied removal efficiencies of Czech WWTPs, which together with the already published literature, gives a more complete picture of the burden on the aquatic environment.

Mutagenicity assessment of two potential impurities in preparations of 5-amino-2,4,6 triiodoisophthalic acid, a key intermediate in the synthesis of the iodinated contrast agent iopamidol.

5-Aminoisophthalic acid and 5-nitroisophthalic acid (5-NIPA) are potential impurities in preparations of 5-amino-2,4,6-triiodoisophthalic acid, which is a key intermediate in the synthesis of the iodinated contrast agent iopamidol. We have studied their mutagenicity in silico (quantitative structure-activity relationships, QSAR) and by the bacterial reverse mutation assay (Ames test). First, the compounds were screened with the tools Derek Nexus™ and Leadscope®. Both compounds were flagged as potentially mutagenic (class 3 under ICH M7). However, contrary to the in silico prediction, neither chemical was mutagenic in the Ames test (plate incorporation method) with or without S9 metabolic activation.

Balloon-Assisted Portal Vein Embolization Using n-Butyl-2-Cyanoacrylate-Lipiodol-Iopamidol Mixture in Swine: A Comparison of 2 Formulations.

PURPOSE: To compare 2 ratios of n-butyl-2-cyanoacrylate (nBCA)-ethiodized oil (Lipiodol)-iopamidol (NLI) in balloon-assisted portal vein embolization (PVE) in swine. MATERIALS AND METHODS: In an in vitro study, NLI prepared at a ratio of 2:3:1 (NLI231) or 1:4:1 (NLI141) was injected into 2.5- or 10-mL syringes filled with swine blood, and the viscosity of NLI was measured to determine an appropriate balloon occlusion time. Two portal vein branches in 8 female swine (n = 16 vein branches) were embolized with NLI231 (n = 8) or NLI141 (n = 8) under balloon occlusion. Portal venography was performed before, immediately after, and 3 days after PVE to evaluate the migration of NLI and the recanalization of embolized portal vein branches. Then, the livers were removed for histopathologic evaluation. RESULTS: The times to peak viscosity of NLI231 in the 2.5- and 10-mL syringes were 55.8 seconds (SD ± 7.0) and 85.2 seconds (SD ± 6.3), and those to peak viscosity of NLI141 were 129.2 seconds (SD ± 11.8) and 254.0 seconds (SD ± 21.8), respectively. No migration of NLI231 was observed in all 8 procedures immediately or 3 days after PVE. Migration of NLI141 was observed in 6 of 8 procedures within 3 days after PVE. The migration frequency of the embolic material was lower in the NI231 group than in the NLI141 group (0/8 vs 6/8; P = .051). Histologically, NLI231 occupied the portal veins without any thrombi, whereas NLI141 was accompanied by thrombi in the portal veins. CONCLUSIONS: NLI231 may be more suitable than NLI141 for balloon-assisted PVE in swine.

[Adsorption of Iopamidol by NaHCO3-activated Buckwheat Biochar].

NaHCO3-activated buckwheat biochar was studied, and an optimal biochar of 0.25N-BC [m(NaHCO3):m(buckwheat bark)=0.25:1]was selected. SEM, BET, XRD, Raman, FTIR, and XPS methods were applied to analyze the effects of NaHCO3 on the physicochemical properties of buckwheat biochar. The adsorption properties and mechanism of NaHCO3-activated buckwheat biochar for iopamidol(IPM), a nonionic iodol X-ray contrast agent, were also investigated. The results showed that compared with buckwheat skin biochar(BC), NaHCO3-activated biochar had higher structural defects(surface area and pore volume increased, respectively, from 480.40 m2·g-1 and 0.29 cm3·g-1 to 572.83 m2·g-1 and 0.40 cm3·g-1, with ID/IG being 1.22 times that of BC), the carbon and oxygen functional groups on the BC surface changed significantly, and the polarity increased [(N+O)/C from 0.15 to 0.24]. The maximum adsorption capacity of 0.25N-BC for IPM was 74.94 mg·g-1, which was 9.51 times that of BC(7.88 mg·g-1). The pseudo-second-order adsorption kinetics and Langmuir and Freundlich isotherm models could well fit the adsorption of 0.25N-BC for IPM. The adsorption processes were mainly chemical, monolayer, and heterogeneous multilayer adsorption. Pore filling, hydrogen bonding, π-π, and n-π interactions were the main mechanisms of 0.25N-BC adsorption for IPM. Comparing the activated buckwheat biochar by different bases [KOH, Na2CO3, NaHCO3, KHCO3, and Ca(HCO3)2], 0.25N-BC exhibited high adsorption capability and short equilibrium time and could effectively remove the IPM residue in the actual water(secondary sedimentation tank effluent and lake). The removal rate of IPM remained at 74.91% after three adsorption-desorption cycles. The results showed that NaHCO3-activated buckwheat biochar was a green, effective, and sustainable adsorbent for the removal of iodine-containing organic matter.

In Vitro Characterization of Drug-Loaded Superabsorbent Polymer Microspheres: Absorption and Release Capacity of Contrast Material, Antibiotics and Analgesics.

PURPOSE: To examine the characteristics of drug-loaded superabsorbent polymer microspheres (SAP-MS) such as drug absorption, drug release, diameter, and visibility. MATERIALS AND METHODS: SAP-MS (HepaSphere150-200 µm; Merit Medical, South Jordan, UT, USA) were suspended in drug solutions: (a) cefazolin, (b) lidocaine, (c) iopamidol and cefazolin, (d) iopamidol and lidocaine, and (e) iopamidol, cefazolin, and lidocaine. The concentrations of drugs were measured, and the amount of each drug absorbed was calculated. Filtered drug-loaded SAP-MS were mixed with saline, and the drug release rates were calculated. The diameter changes of SAP-MS during absorption were observed. Radiography of drug-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio (CNR). RESULTS: The drug concentration did not change during absorption. The release rates increased for 10 min and then came to an equilibrium. The mean amounts of drug absorbed at 180 min and mean release rates at 24 h were (a) cefazolin: 265.4 mg, 64.2%; (b) lidocaine: 19.6 mg, 75.6%; (c) iopamidol: 830.2 mg, 22.5%; cefazolin: 137.6 mg, 21.2%; (d) iopamidol: 1620.6 mg, 78.5%; lidocaine: 13.5 mg, 81.4%; and (e) iopamidol: 643.7 mg, 52.9%; cefazolin: 194.0 mg, 51.6%; lidocaine: 5.3 mg, 58.4%. The diameter of SAP-MS increased for approximately 15 min. Finally, the diameters of SAP-MS were (a) 3.9 times, (b) 5.0 times, (c) 2.2 times, (d) 5.5 times, and (e) 3.6 times larger than the original size. Drug-loaded SAP-MS containing iopamidol were visible under X-ray imaging, with CNRs of (c) 3.0, (d) 9.0, and (e) 4.5. CONCLUSION: SAP-MS can absorb and release iopamidol, cefazolin, and lidocaine.

Differences in radiopacity among CT contrast agents and concentrations: A quantitative study.

BACKGROUND AND PURPOSE: Several studies in the literature have attempted to subjectively assess the degree of visualization of different neurovascular structures using different contrast agents and concentrations. Given the recent contrast shortages, we aim to objectively compare the radiopacity achieved with four angiographic contrast agents used in clinical practice. METHODS: Isovue 370, Visipaque 320, Omnipaque 300, and Isovue 300 were each drawn up at 25%, 50%, 75%, and 100% concentrations and compared against normal saline and air syringes. CT scans were obtained, and regions of interest were analyzed for radiopacity using Hounsfield unit (HU) measurements. An aneurysm model with different contrast concentrations was also scanned and dimensions compared. Two-tailed t-tests and Cohen's d coefficients were applied to assess for differences in mean HU measurements. RESULTS: Isovue 370 and Isovue 300 had the highest and lowest mean HU, respectively (p < .001). Visipaque 320 at 25% concentration had the lowest mean HU at -.76. Statistically similar agents (p < .05) were Visipaque 320 and Omnipaque 300 at a 100% concentration (p = .30), and Omnipaque 300 and Isovue 300 at a 25% concentration (p = .73). Aneurysm dimensions among Isovue 370, Visipaque 320, and Omnipaque 300 were all similar, whereas with Isovue 300, the dimensions were significantly smaller (p < .05). CONCLUSION: Isovue 370 provides the highest HU radiopacity and the most accurate aneurysm measurements. Angiographic measurements obtained with Isovue 300 may underestimate the actual aneurysmal dimensions. Visipaque 320 and Omnipaque 300 at 100% concentration have similar mean HUs and are beneficial for patients with chronic kidney or cardiac disease.

Rostral spread of lumbosacral epidural volumes of dye and contrast medium calculated using body weight or length of the vertebral column in dog cadavers.

The objective of this study was to compare the rostral spread of lumbosacral epidural volumes of a mixture of dye and contrast medium, calculated using body weight (BW) or vertebral column length (LE), in 22 dog cadavers. The dogs weighed 4.6 to 52.0 kg. Dogs were paired within a < 10% difference for BW and LE and with the same body condition score (BCS). Pairs of dogs were injected while in sternal recumbency through an epidural catheter with a volume mixture of iopamidol and dye, calculated based on BW: 0.2 mL/kg in one of the cadavers and based on LE: 0.05 mL/cm (< 50 cm), 0.07 mL/cm (50 to < 70 cm), 0.08 mL/cm (70 to < 80 cm), and 0.11 mL/cm (≥ 80 cm) in the other cadaver. The extent of rostral spread was determined using computed tomography for iopamidol and anatomical dissection for dye. Comparisons for dye and iopamidol within each dog, and for BW and LE within matched pairs, were completed with mixed linear models (P < 0.05). The number of vertebrae reached by dye was greater than the number reached by iopamidol in both BW and LE, but the rostral spread was not significantly different between BW and LE for all pairs. In conclusion, dye tends to spread further than iopamidol and therefore, these two methods should not be considered interchangeable when used in research studies.

L'objectif de cette étude était de comparer l'étalement rostral des volumes épiduraux lombo-sacrés d'un mélange de colorant et de produit de contraste, calculé en utilisant le poids corporel (PC) ou la longueur de la colonne vertébrale (LE), chez 22 cadavres de chiens. Les chiens pesaient de 4,6 à 52,0 kg. Les chiens ont été appariés avec une différence < 10 % pour PC et LE et avec le même score d'état corporel (PCS). Des paires de chiens ont reçu une injection alors qu'ils étaient en décubitus sternal à travers un cathéter péridural avec un mélange volumique d'iopamidol et de colorant, calculé sur la base du poids corporel : 0,2 mL/kg dans l'un des cadavres et sur la base de la LE : 0,05 mL/cm (< 50 cm), 0,07 mL/cm (50 à < 70 cm), 0,08 mL/cm (70 à < 80 cm) et 0,11 mL/cm (≥ 80 cm) dans l'autre cadavre. L'étendue de la propagation rostrale a été déterminée par tomodensitométrie pour l'iopamidol et dissection anatomique pour le colorant. Les comparaisons pour le colorant et l'iopamidol au sein de chaque chien, et pour PC et LE au sein de paires appariées, ont été complétées avec des modèles linéaires mixtes (P < 0,05). Le nombre de vertèbres atteintes par le colorant était supérieur au nombre atteint par l'iopamidol dans PC et LE, mais la propagation rostrale n'était pas significativement différente entre PC et LE pour toutes les paires. En conclusion, le colorant a tendance à se propager plus loin que l'iopamidol et, par conséquent, ces deux méthodes ne doivent pas être considérées comme interchangeables lorsqu'elles sont utilisées dans des études de recherche.(Traduit par Docteur Serge Messier).

Comparison of rostral spread of lumbosacral epidural volume calculated by body weight or length of the vertebral column in small-sized anesthetized dogs.

The first objective of this prospective, randomized, crossover experimental trial was to compare the rostral spread of lumbosacral epidural volume calculated by body weight (BW) or vertebral column length (LE) in 6 small, isoflurane-anesthetized female beagle dogs (BW: 7.5 to 10.2 kg; LE measured from the occipital crest to the sacrococcygeal space: 46 to 56 cm). The second objective was to assess the response to a noxious stimulus once the dogs recovered from anesthesia and to determine the effects of the injection on cardiopulmonary variables. While in sternal position, dogs were injected through an epidural catheter with a volume mixture of bupivacaine 0.25% and iopamidol 15% based on BW: 0.2 mL/kg or LE: 0.05 mL/cm (< 50 cm) or 0.07 mL/cm (50 to < 70 cm). Rostral spread was determined by counting the number of vertebrae reached by iopamidol using computed tomography. After anesthesia, cardiopulmonary variables, motor function, and responses to nociceptive stimuli were evaluated. Comparisons were completed with mixed linear models and 2-way analysis of variance (ANOVA) (P < 0.05). The volume of injectate (3.29 ± 0.74 versus 1.81 ± 0.21 mL; mean ± SD) and the number of vertebrae (22 ± 2 versus 19 ± 2 vertebrae) reached by iopamidol were significantly greater for LE than for BW. Response to nociception, time to return of pain sensation, motor function, and cardiopulmonary variables were similar between groups. In conclusion, dosing based on LE resulted in larger rostral spread than when based on BW in dogs of small size.

Le premier objectif de cet essai expérimental croisé prospectif randomisé était de comparer la propagation rostrale du volume épidural lombo-sacré calculé en fonction du poids corporel (PC) ou de la longueur de la colonne vertébrale (LE) chez 6 petites chiennes beagle anesthésiées à l'isoflurane (PC : 7,5 à 10,2 kg; LE mesuré de la crête occipitale à l'espace sacro-coccygien : 46 à 56 cm). Le deuxième objectif était d'évaluer la réponse à un stimulus nocif une fois que les chiens se sont remis de l'anesthésie et de déterminer les effets de l'injection sur les variables cardiopulmonaires. En position sternale, les chiens ont reçu une injection via un cathéter péridural d'un mélange volumique de bupivacaïne à 0,25 % et d'iopamidol à 15 % basé sur le poids corporel : 0,2 mL/kg ou LE : 0,05 mL/cm (< 50 cm) ou 0,07 mL/cm (50 à < 70 cm). La propagation rostrale a été déterminée en comptant le nombre de vertèbres atteintes par l'iopamidol en utilisant la tomodensitométrie. Après l'anesthésie, les variables cardiopulmonaires, la fonction motrice et les réponses aux stimuli nociceptifs ont été évaluées. Les comparaisons ont été complétées avec des modèles linéaires mixtes et une analyse de variance à 2 facteurs (ANOVA) (P < 0,05). Le volume d'injectat (3,29 ± 0,74 versus 1,81 ± 0,21 mL; moyenne ± SD) et le nombre de vertèbres (22 ± 2 versus 19 ± 2 vertèbres) atteints par l'iopamidol étaient significativement plus élevés pour LE que pour BW. La réponse à la nociception, le temps de retour de la sensation de douleur, la fonction motrice et les variables cardiopulmonaires étaient similaires entre les groupes. En conclusion, le dosage basé sur LE a entraîné une plus grande propagation rostrale que lorsqu'il était basé sur BW chez les chiens de petite taille.(Traduit par Docteur Serge Messier).

Development of cationic peptide-based hydrogels loaded with iopamidol for CEST-MRI detection.

Peptide-based hydrogels have been recently investigated as materials for biomedical applications like tissue engineering and delivery of drugs and imaging agents. Among the synthetic peptide hydrogelators, the cationic hexapeptides Ac-K1 and Ac-K2 were proposed as scaffolds for bioprinting applications. Here, we report the formulation of Ac-K1 and Ac-K2 hydrogels loaded with iopamidol, an iodinated contrast agent clinically approved for X-ray computed tomography, and more recently identified as an efficient CEST-MRI probe. Iopamidol-loaded hydrogels were soft, injectable and non-toxic both in vitro (on three tumor cell lines: GL261, TS/A and 3T3-NIH) and in vivo (in Balb/c mice inoculated with TS/A breast cancer cells). The in vitro CEST-MRI study evidenced the typical features of the CEST pattern of iopamidol, with a CEST contrast higher than 50%. Due to their injectability and good ability to retain the contrast agent, the herein investigated systems can be considered as promising candidates for the development of smart MRI detectable hydrogels.

A machine learning approach that measures pH using acidoCEST MRI of iopamidol.

Tumor acidosis is an important biomarker for aggressive tumors, and extracellular pH (pHe) of the tumor microenvironment can be used to predict and evaluate tumor responses to chemotherapy and immunotherapy. AcidoCEST MRI measures tumor pHe by exploiting the pH-dependent chemical exchange saturation transfer (CEST) effect of iopamidol, an exogenous CT agent repurposed for CEST MRI. However, all pH fitting methodologies for acidoCEST MRI data have limitations. Herein we present results of the application of machine learning for extracting pH values from CEST Z-spectra of iopamidol. We acquired 36,000 experimental CEST spectra from 200 phantoms of iopamidol prepared at five concentrations, five T1 values, and eight pH values at five temperatures, acquired at six saturation powers and six saturation times. We also acquired T1 , T2 , B1 RF power, and B0 magnetic field strength supplementary MR information. These MR images were used to train and validate machine learning models for the tasks of pH classification and pH regression. Specifically, we tested the L1-penalized logistic regression classification (LRC) model and the random forest classification (RFC) model for classifying the CEST Z-spectra for thresholds at pH 6.5 and 7.0. Our results showed that both RFC and LRC were effective for pH classification, although the RFC model achieved higher predictive value, and improved the accuracy of classification accuracy with CEST Z-spectra with a more limited set of saturation frequencies. Furthermore, we used LASSO and random forest regression (RFR) models to explore pH regression, which showed that the RFR model achieved higher accuracy and precision for estimating pH across the entire pH range of 6.2-7.3, especially when using a more limited set of features. Based on these results, machine learning for analysis of acidoCEST MRI is promising for eventual in vivo determination of tumor pHe.

Improving pulmonary perfusion assessment by dynamic contrast-enhanced computed tomography in an experimental lung injury model.

Pulmonary perfusion has been poorly characterized in acute respiratory distress syndrome (ARDS). Optimizing protocols to measure pulmonary blood flow (PBF) via dynamic contrast-enhanced (DCE) computed tomography (CT) could improve understanding of how ARDS alters pulmonary perfusion. In this study, comparative evaluations of injection protocols and tracer-kinetic analysis models were performed based on DCE-CT data measured in ventilated pigs with and without lung injury. Ten Yorkshire pigs (five with lung injury, five healthy) were anesthetized, intubated, and mechanically ventilated; lung injury was induced by bronchial hydrochloric acid instillation. Each DCE-CT scan was obtained during a 30-s end-expiratory breath-hold. Reproducibility of PBF measurements was evaluated in three pigs. In eight pigs, undiluted and diluted Isovue-370 were separately injected to evaluate the effect of contrast viscosity on estimated PBF values. PBF was estimated with the peak-enhancement and the steepest-slope approach. Total-lung PBF was estimated in two healthy pigs to compare with cardiac output measured invasively by thermodilution in the pulmonary artery. Repeated measurements in the same animals yielded a good reproducibility of computed PBF maps. Injecting diluted isovue-370 resulted in smaller contrast-time curves in the pulmonary artery (P < 0.01) and vein (P < 0.01) without substantially diminishing peak signal intensity (P = 0.46 in the pulmonary artery) compared with the pure contrast agent since its viscosity is closer to that of blood. As compared with the peak-enhancement model, PBF values estimated by the steepest-slope model with diluted contrast were much closer to the cardiac output (R2 = 0.82) as compared with the peak-enhancement model. DCE-CT using the steepest-slope model and diluted contrast agent provided reliable quantitative estimates of PBF.NEW & NOTEWORTHY Dynamic contrast-enhanced CT using a lower-viscosity contrast agent in combination with tracer-kinetic analysis by the steepest-slope model improves pulmonary blood flow measurements and assessment of regional distributions of lung perfusion.

Clinical features and risk factors of iodinated contrast media (ICM)-induced anaphylaxis.

PURPOSE: To evaluate the clinical features and risk factors of iodinated contrast media (ICM)-induced anaphylaxis. METHODS: This retrospective study included all patients undergoing contrast-enhanced computed tomography (CT) with intravenous ICM administration (iopamidol, iohexol, iomeprol, iopromide, ioversol) at our hospital between April 2016 and September 2021. Medical records of patients who experienced anaphylaxis were reviewed, and the multivariable regression model using generalized estimating equations was employed to eliminate the effect of intrapatient correlation. RESULTS: Of the 76,194 ICM administrations (44,099 men [58 %] and 32,095 women; age, median, 68 years) to 27, 696 patients, anaphylaxis occurred in 45 cases in 45 different patients (0.06 % of administration and 0.16 % of patients), all with onset within 30 min after administration. Thirty-one (69 %) had no risk factors for ADRs, including 14 (31 %) who had previously used the same ICM that caused anaphylaxis. Thirty-one patients (69 %) had a history of ICM use without any ADRs. Four patients (8.9 %) received oral steroid premedication. The only factor associated with anaphylaxis was the type of ICM, with an odds ratio (OR) of 6.8 (p < 0.001) for iomeprol with iopamidol as a reference. No significant differences in OR of anaphylaxis were found for patients' age, sex, or premedication. CONCLUSION: The overall incidence of anaphylaxis due to ICM was very low. More than half of the cases had no risk factors for ADRs and had no ADRs on past ICM administration, although the ICM type was associated with a higher OR.

Disinfection byproducts of iopamidol, iohexol, diatrizoate and their distinct acute toxicity on Scenedesmus sp., Daphnia magna and Danio rerio.

The COVID-19 pandemic resulted in increasing the usage of iodinated contrast media (ICM), and thus an increase in the prevalence of ICM-contaminated wastewater. While ICM is generally safe, this has the potential to be problematic because as medical wastewater is treated and disinfected, various ICM-derived disinfection byproducts (DBPs) may be generated and released into the environment. However, little information was available about whether ICM-derived DBPs are toxic to aquatic organisms. In this study, the degradation of three typical ICM (iopamidol, iohexol, diatrizoate) at initial concentration of 10 µM and 100 µM in chlorination and peracetic acid without or with NH4+ was investigated, and the potential acute toxicity of treated disinfected water containing potential ICM-derived DBPs on Daphnia magna, Scenedesmus sp. and Danio rerio was tested. The degradation results suggested that only iopamidol was significantly degraded (level of degradation >98%) by chlorination, and the degradation rate of iohexol and diatrizoate were significantly increased in chlorination with NH4+. All three ICM were not degraded in peracetic acid. The toxicity analysis results indicate that only the disinfected water of iopamidol and iohexol by chlorination with NH4+ were toxic to at least one aquatic organism. These results highlighted that the potential ecological risk of ICM-contained medical wastewater by chlorination with NH4+ should not be neglected, and peracetic acid may be an environment-friendly alternative for the disinfection of wastewater containing ICM.

Effects of contrast medium viscosity into flushing port on artefacts during optical coherence tomography imaging.

BACKGROUND: Optical coherence tomography (OCT) is becoming the standard imaging modality for percutaneous coronary intervention (PCI) because of its high resolution. To perform appropriate OCT-guided PCI, it is necessary to avoid artefacts and obtain high-quality images. We investigated the relationship between artefacts and the viscosity of contrast media, which were used to remove air before OCT imaging catheter was inserted into guiding catheter. METHODS: We retrospectively analyzed every pullback of OCT examinations from January 2020 to September 2021. Cases were divided into two groups according to the type of contrast media used for catheter flushing: low-viscosity (Iopamidol-300, Bayer, Nordrhein-Westfalen, Germany) vs. high-viscosity (Iopamidol-370, Bayer). We evaluated the artefacts and quality of each OCT image and performed ex vivo experiments to compare differences in artefact frequencies using the two contrast media. RESULTS: A total of 140 pullbacks in the low-viscosity group and 73 pullbacks in the high-viscosity group were analyzed. The percentage of grade 2 and 3 images (with good quality) in the low-viscosity group was significantly lower (68.1 % vs. 94.5 %, p < 0.001). Rotational artefacts were significantly more common in the low-viscosity group (49.3 % vs. 8.2 %, p < 0.001). In multivariate analysis, using low-viscosity contrast media was a significant factor influencing the appearance of rotational artefacts and affecting image quality (odds ratio, 9.42; 95 % confidence interval, 3.58 to 24.8; p < 0.001). In ex vivo experiments, using low-viscosity contrast media was also a significant predictor of artefact occurrence during OCT (p < 0.01). CONCLUSIONS: The viscosity of the contrast agent used while flushing the OCT imaging catheter contributes to the appearance of OCT artefacts.

Contrast Agent Selection to Prevent Recurrent Severe Hypersensitivity Reaction to Iodinated Contrast Media Based on Nationwide Database.

OBJECTIVE: To investigate the incidence of severe iodinated contrast media (ICM)-related hypersensitivity reaction (HSR) and to find the optimal alternative ICM to reduce the risk of severe HSR recurrence. METHODS: We retrospectively reviewed 23,383,183 cases of ICM administration between January 2015 and December 2019 from the nationwide health insurance database. We classified ICMs based on generic profiles and the presence of N-(2,3-dihydroxypropyl) carbamoyl side chains. The incidence of severe and recurrent severe HSRs was calculated, and χ2 tests were performed to compare the prevalence of severe HSR according to ICM groups. In addition, logistic regression analyses were used to assess differences between ICM groups. RESULTS: The incidence of severe HSRs was 1.92% (450,067 of 23,282,183). Among 1,875,245 individuals who received ICM twice on different days, severe HSR occurred in 40,850 individuals, and severe HSR recurred in 3319 individuals (8.12%). The risk of recurrence significantly decreased when the ICM changed (9.24% vs 7.08%, P < 0.001), especially when the ICM changed to one with a different side chain (6.74%, P < 0.001). In addition, compared with the reuse of the culprit agent, using combinations of iobitridol/iohexol (odds ratio [OR], 0.696; P = 0.04), iohexol/iopamidol (OR, 0.757; P = 0.007), iopamidol/iohexol (OR, 0.447; P < 0.001), and ioversol/iohexol (OR, 0.683; P = 0.04) reduced the risk of recurrence of severe HSR. CONCLUSIONS: Changing the culprit ICM to that with a different side chain can reduce severe HSR recurrence. The optimal choice of an alternative ICM depends on the causative agent.

Investigating the biodegradability of iodinated X-ray contrast media in simultaneous nitrification and denitrification system.

The present study investigated the biodegradation of three iodinated X-ray contrast media (ICM), namely, iopamidol, iohexol, and iopromide, in simultaneous nitrification-denitrification (SND) system maintained in a sequencing batch reactor (SBR). The results showed that variable aeration patterns (anoxic-aerobic-anoxic) and micro-aerobic condition were most effective in the biotransformation of ICM while achieving organic carbon and nitrogen removal. The highest removal efficiencies of iopamidol, iohexol, and iopromide were 48.24%, 47.75%, and 57.46%, respectively, in micro-aerobic condition. Iopamidol was highly resistant to biodegradation and possessed the lowest Kbio value, followed by iohexol and iopromide, regardless of operating conditions. The removal of iopamidol and iopromide was affected by the inhibition of nitrifiers. The transformation products after hydroxylation, dehydrogenation, and deiodination of ICM were detected in the treated effluent. Due to the addition of ICM, the abundance of denitrifier genera Rhodobacter and Unclassified Comamonadaceae increased, and the abundance of class TM7-3 decreased. The presence of ICM affected the microbial dynamics, and the diversity of microbes in SND resulted in improving the biodegradability of the compounds.

Nephrotoxicity of iopamidol is associated with mitochondrial impairment in human cell and teleost models.

Iopamidol is a nonionic, low-osmolar iodinated contrast agent used for angiography. Its clinical use is associated with renal dysfunction. Patients suffering from preexisting kidney disease have an increased risk of renal failure upon iopamidol administration. Studies in animals confirmed renal toxicity, but the involved mechanisms remain unclear. Therefore, the aim of the present study was to use human embryonic kidney cells (HEK293T) as a general cell model of mitochondrial damage, as well as, zebrafish larvae, and isolated proximal tubules of killifish to investigate factors promoting renal tubular toxicity of iopamidol with a focus on mitochondrial damage. Results from in vitro HEK293T cell-based assays indicate that iopamidol affects mitochondrial function Treatment with iopamidol induces ATP depletion, reduces the mitochondrial membrane potential, and elevates mitochondrial superoxide and reactive oxygen species accumulation. Similar results were obtained with gentamicin sulfate and cadmium chloride, two well-known model compounds associated with renal tubular toxicity. Confocal microscopy confirms changes in mitochondrial morphology, such as mitochondrial fission. Importantly, these results were confirmed in proximal renal tubular epithelial cells using ex vivo and in vivo teleost models. In conclusion, this study provides evidence for iopamidol-induced mitochondrial damage in proximal renal epithelial cells. Teleost models allow studying proximal tubular toxicity with translational relevance for humans.

Computed tomographic lymphangiography following percutaneous intrahepatic injection of iopamidol in cats.

OBJECTIVE: To determine if computed tomographic lymphangiography (CTL) after ultrasound-guided percutaneous injection of intrahepatic iopamidol (Isovue 370) in healthy cats would safely and effectively lead to opacification of the hepatic lymphatics, cisterna chyli, and thoracic ducts (TDs). STUDY DESIGN: A prospective pilot study design with randomization of the sides of the liver injected. SAMPLE POPULATION: 6 purpose-bred cats. PROCEDURES: Cats were anesthetized and based on random assignment, and the left or right liver was injected with iodinated contrast material. CTL images were taken at 5, 10, and 15 minutes postinjection to determine the quality of opacification of the cisterna chyli and TDs. RESULTS: Eleven hepatic injections from 6 cats were available for review. One CT file was corrupted and unusable. Seven out of 11 hepatic contrast injections yielded a diagnostic study. Five out of 11 were graded as excellent, 0/11 were graded as good, and 2/11 were graded as fair. Opacification of the cisterna chyli and TDs was absent in 4/11 studies. Three out of 6 cats had mild to moderate increases in hepatocellular enzymes when assayed 3 months postprocedure. The hepatic lymphatics, cisterna chyli, and TDs were opacified in all studies deemed diagnostic. CLINICAL RELEVANCE: Intrahepatic contrast injection offers a novel portal for thoracic duct lymphangiography that documents the hepatic contribution to the mesenteric lymphatics, cisterna chyli, and thoracic duct. The procedure may be helpful in the preoperative diagnostic evaluation of cats with chylothorax.

Intraperitoneal Delivery of Iopamidol to Assess Extracellular pH of Orthotopic Pancreatic Tumor Model by CEST-MRI.

The extracellular pH (pHe) of solid tumors is often acidic, as a consequence of the Warburg effect, and an altered metabolic state is often associated with malignancy. It has been shown that acidosis can promote tumor progression; thus, many therapeutic strategies have been adopted against tumor metabolism; one of these involves alkalinization therapies to raise tumor pH to inhibit tumor progression, improve immune surveillance, and overcome resistance to chemotherapies. Chemical exchange saturation transfer-magnetic resonance imaging (CEST-MRI) is a noninvasive technique that can measure pH in vivo using pH-sensitive contrast agents. Iopamidol, an iodinated contrast agent, clinically used for computed tomography (CT), contains amide group protons with pH-dependent exchange rates that can reveal the pHe of the tumor microenvironment. In this study, we optimized intraperitoneal (IP) delivery of iopamidol to facilitate longitudinal assessments of orthotopic pancreatic tumor pHe by CEST-MRI. Following IV-infusion and IP-bolus injections, we compared the two protocols for assessing tumor pH. Time-resolved CT imaging was used to evaluate the uptake of iopamidol in the tumor, revealing that IP-bolus delivered a high amount of contrast agent 40 min postinjection, which was similar to the amounts reached with the IV-infusion protocol. As expected, both IP and IV injection protocols produced comparable measurements of tumor pHe, showing no statistically significant difference between groups (p=0.16). In addition, we showed the ability to conduct longitudinal monitoring of tumor pHe using CEST-MRI with the IP injection protocol, revealing a statistically significant increase in tumor pHe following bicarbonate administration (p < 0.001). In conclusion, this study shows the capability to measure pHe using an IP delivery of iopamidol into orthotopic pancreatic tumors, which is important to conduct longitudinal studies.