Adverse reactions after intravascular iodinated contrast media administration and their management.

Endovascular interventions and diagnostic examinations using iodinated contrast media (ICM) are standard of care in current vascular medicine. Although ICM use is generally considered safe, it may be associated with adverse reactions, vary from minor disturbances to rare, but severe life-threatening complications. This position paper of European Society of Vascular Medicine integrates current knowledge and summarizes the key information related to the use of intravascular ICM, serving as recommendation on prevention and management of acute, late, and very late adverse reactions. It should help the health professionals in all fields of vascular medicine to make decisions in daily practice for safe use of contrast media.

Elevated levels of iodide promote peroxidase-mediated protein iodination and inhibit protein chlorination.

At inflammatory sites, immune cells generate oxidants including H2O2. Myeloperoxidase (MPO), released by activated leukocytes employs H2O2 and halide/pseudohalides to form hypohalous acids that mediate pathogen killing. Hypochlorous acid (HOCl) is a major species formed. Excessive or misplaced HOCl formation damages host tissues with this linked to multiple inflammatory diseases. Previously (Redox Biology, 2020, 28, 101331) we reported that iodide (I⁻) modulates MPO-mediated protein damage by decreasing HOCl generation with concomitant hypoiodous acid (HOI) formation. HOI may however impact on protein structure, so in this study we examined whether and how HOI, from peroxidase/H2O2/I⁻ systems ± Cl⁻, modifies proteins. Experiments employed MPO and lactoperoxidase (LPO) and multiple proteins (serum albumins, anastellin), with both chemical (intact protein and peptide mass mapping, LC-MS) and structural (SDS-PAGE) changes assessed. LC-MS analyses revealed dose-dependent iodination of anastellin and albumins by LPO/H2O2 with increasing I⁻. Incubation of BSA with MPO/H2O2/Cl⁻ revealed modest chlorination (Tyr286, Tyr475, ∼4 %) and Met modification. Lower levels of these species, and extensive iodination at specific Tyr and His residues (>20 % modification with ≥10 µM I⁻) were detected with increasing I⁻. Anastellin dimerization was inhibited by increasing I⁻, but less marked changes were observed with albumins. These data confirm that I⁻ competes with Cl⁻ for MPO and is an efficient HOCl scavenger. These processes decrease protein chlorination and oxidation, but result in extensive iodination. This is consistent with published data on the presence of iodinated Tyr on neutrophil proteins. The biological implications of protein iodination relative to chlorination require further clarification.

Harmful effect of repetitive intravenous iodinated contrast media administration on the long-term renal function of patients with early gastric cancer.

This retrospective study investigated whether repetitive exposure to intravenous iodinated contrast media (ICM) affects long-term renal function in patients who undergo curative surgery for early gastric cancer (EGC) collected from the Korean Health Insurance and Review Assessment (HIRA) database. Patients diagnosed with gastric cancer between January 2010 and December 2013 underwent regular computed tomography (CT) scans to monitor for extragastric recurrence. Patients who already had chronic kidney disease (CKD) before cancer diagnosis or had undergone chemotherapy or repeated surgery were excluded. A nested case-control study design was chosen to analyze the effect of repetitive ICM exposure to long-term renal function by comparing patients who developed CKD 2 years after cancer diagnosis and patients who did not. Among 59,971 patients collected according to inclusion and exclusion criteria, 1021 were diagnosed with CKD 2 years after cancer diagnosis. Using 1:5 matching after adjusting for age, sex and date of cancer diagnosis, 5097 control patients were matched to 1021 CKD patients. Conditional logistic regression showed that the number of CTs taken using ICM slightly increased the odds of CKD (odds ratio, 1.080; 95% confidence interval (CI): 1.059, 1.100; P < 0.0001). Thus, the administration of ICM might contribute to chronic renal function impairment.

Multifunctionality of Iodinated Halogen-Bonded Polymer: Biodegradability, Radiopacity, Elasticity, Ductility, and Self-Healing Ability.

A polymer with high contents of ester bonds and iodine atoms was synthesized, exhibiting sufficient biodegradability and radioactivity for biomedical applications. The iodine moieties of the synthesized polyester can generate halogen bonding between molecules, which may develop additional functional properties through the bonding. In this study, poly(glycerol adipate) (PGA) was selected and synthesized as a polyester, which was then adequately conjugated with three different types of iodine compounds via the hydroxy groups of PGA. It was found that the iodine compounds could effectively work as donors of halogen bonding. The thermal analysis by differential scanning calorimetry (DSC) revealed that the glass transition temperature increased with the increase in the strength of interactions caused by π-π stacking and halogen bonding, eventually reaching 49.6 °C for PGA with triiodobenzoic groups. An elastomeric PGA with monoiodobenzoic groups was also obtained, exhibiting a high self-healing ability at room temperature because of the reconstruction of halogen bonding. Such multifaceted performance of the synthesized polyester with controllable thermal/mechanical properties was realized by halogen bonding, leading to a promising biomaterial with multifunctionality.

Skin Test-Guided Strategy to Select Alternative Iodinated Contrast Media in Patients With Immediate Hypersensitivity Reaction: A Prospective Confirmative Study.

BACKGROUND: Iodinated contrast media (ICM) are a common cause of drug-induced immediate hypersensitivity reaction (IHR). Repeated use of ICM is often necessary; therefore, a standardized protocol to prevent recurrence of IHR is required. OBJECTIVE: We aimed to propose an intradermal skin test (IDT)-guided strategy for previous reactors to prevent recurrence of IHR. METHODS: We conducted a prospective multicenter study from May 2018 to December 2020 and recruited patients who had experienced IHR to ICM. Once enrolled, the participants underwent IDT with a causative ICM. The alternatives for reexposure were selected using the following protocol: (1) if the IDT with the culprit ICM was positive, further skin tests with other available ICM were conducted to choose IDT-negative agents as alternatives, and (2) if the IDT with the culprit ICM was negative, a randomly changed ICM was used without additional skin tests. The recurrence and severity of hypersensitivity were assessed in subsequent computed tomography examinations. Premedication was administered according to the severity of the index event in all cases. RESULTS: A total of 496 participants were enrolled, and 299 were reexposed to ICM. Among 269 participants who followed the protocol, 228 (84.8%) completed computed tomography examinations without adverse reactions, and IHR recurred in 16 of 30 participants (53.3%) who did not follow the protocol (P < .001). In addition, application of the protocol reduced the severity of IHR in recurred cases (P = 0.003). CONCLUSIONS: Our IDT-guided strategy not only reduced recurrence of IHR to ICM but also mitigated the severity in recurred cases. This provides evidence for recommending an IDT to diagnose ICM allergy and find safe alternatives.

Iodine Biofortification of Dandelion Plants (Taraxacum officinale F.H. Wiggers Coll.) with the Use of Inorganic and Organic Iodine Compounds.

Iodine is a crucial microelement necessary for the proper functioning of human and animal organisms. Plant biofortification has been proposed as a method of improving the iodine status of the population. Recent studies in that field have revealed that iodine may also act as a beneficial element for higher plants. The aim of the work was to evaluate the efficiency of the uptake and accumulation of iodine in the plants of dandelion grown in a pot experiment. During cultivation, iodine was applied through fertigation in inorganic (KI, KIO3) and organic forms (5-iodosalicylic acid, 5-ISA; 3,5-diiodosalicylic acid, 3,5-diISA) at two concentrations (10 and 50 µM). The contents of total iodine and iodosalicylic acids, as well the plant biomass and antioxidant capacity of dandelion leaves and roots, were analyzed. The uptake of inorganic and organic forms by dandelion plants was confirmed with no negative effect on plant growth. The highest efficiency of improving iodine content in dandelion leaves and roots was noted for 50 µM KI. The applicability of iodosalicylates, especially 5-ISA, for plant biofortification purposes was confirmed, particularly as the increase in the iodine content after the application of 5-ISA was higher as compared to that with commonly used KIO3. The chemical analyses have revealed that iodosalicylates are endogenous compounds of dandelion plants.

Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.

BACKGROUND: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients. OBJECTIVES: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. METHODS: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. RESULTS: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. CONCLUSIONS: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.

Transcriptomic and metabolic studies on the role of inorganic and organic iodine compounds in lettuce plants.

Iodine (I) is considered a beneficial element or even micronutrient for plants. The aim of this study was to determine the molecular and physiological processes of uptake, transport, and metabolism of I applied to lettuce plants. KIO3, KIO3 + salicylic acid, 5-iodosalicylic acid and 3,5-diiodosalicylic acid were applied. RNA-sequencing was executed using 18 cDNA libraries constructed separately for leaves and roots from KIO3, SA and control plants. De novo transcriptome assembly generated 1937.76 million sequence reads resulting in 27,163 transcripts with N50 of 1638 bp. 329 differentially expressed genes (DEGs) in roots were detected after application of KIO3, out of which 252 genes were up-regulated, and 77 were down-regulated. In leaves, 9 genes revealed differential expression pattern. DEGs analysis indicated its involvement in such metabolic pathways and processes as: chloride transmembrane transport, phenylpropanoid metabolism, positive regulation of defense response and leaf abscission, and also ubiquinone and other terpenoid-quinone biosynthesis, protein processing in endoplasmic reticulum, circadian rhythm including flowering induction as well as a putative PDTHA (i.e. Plant Derived Thyroid Hormone Analogs) metabolic pathway. qRT-PCR of selected genes suggested their participation in the transport and metabolism of iodine compounds, biosynthesis of primary and secondary metabolites, PDTHA pathway and flowering induction.

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.

Shortage of iodinated contrast media: Status and possible chances - A systematic review.

PURPOSE: Covid-19 related lockdowns have resulted in a shortage of iodinated contrast media (ICM) in 2022. Health care providers have reacted with implementing conservation strategies to stay operational without compromising patient care. Although articles describing the implemented Interventions have been published, possible chances of the shortage have not yet been mentioned in the literature. METHODS: We conducted a literature search in PubMed and Google Scholar, and analysed the background, interventions, and possible benefits of low-dose ICM regimens. RESULTS: We included 22 articles dealing with "ICM shortage" for the analysis. The delivery bottlenecks in the USA and Australia led to two different countermeasures, 1. reduction of the number of contrast-enhanced image-guided examinations and 2. reduction of the (single) ICM dose. Interventions from both groups have resulted in significant reduction of ICM usage; however, group 1 has contributed more to overall ICM reduction. As benefit of the ICM reduction, we revealed an increased safety for patients at risk (e.g. hypersensitivity reactions, contrast-induced acute kidney injury, thyroid toxic effects). CONCLUSION: The ICM shortage of 2022 has forced health care providers to implement conservation strategies to stay operational. Although there were already proposals for dose reduction before the corona pandemic and the associated supply bottlenecks, this situation led to the use of a reduced amount of contrast agent on a large scale. This presents a good opportunity to reconsider protocols and the use of contrast-enhanced imaging in general for future practice as it offers chances and advantages regarding costs, environmental impact, and patient safety.

Hydrogen iodide (HI) neutral beam etching characteristics of InGaN and GaN for micro-LED fabrication.

We investigated the etching characteristics of hydrogen iodide (HI) neutral beam etching (NBE) of GaN and InGaN and compared with Cl2NBE. We showed the advantages of HI NBE versus Cl2NBE, namely: higher InGaN etch rate, better surface smoothness, and significantly reduced etching residues. Moreover, HI NBE was suppressed of yellow luminescence compared with Cl2plasma. InClxis a product of Cl2NBE. It does not evaporate and remains on the surface as a residue, resulting in a low InGaN etching rate. We found that HI NBE has a higher reactivity with In resulting in InGaN etch rates up to 6.3 nm min-1, and low activation energy for InGaN of approximately 0.015 eV, and a thinner reaction layer than Cl2NBE due to high volatility of In-I compounds. HI NBE resulted in smoother etching surface with a root mean square average (rms) of 2.9 nm of HI NBE than Cl2NBE (rms: 4.3 nm) with controlled etching residue. Moreover, the defect generation was suppressed in HI NBE compared to Cl2plasma, as indicated by lower yellow luminescence intensity increase after etching. Therefore, HI NBE is potentially useful for high throughput fabrication ofµLEDs.

CHRONIC EFFECTS OF CADMIUM CHLORIDE ON RAT EMBRYOGENESIS.

The purpose of this study was to analyze the effects of cadmium toxicity on rat embryogenesis when exposed to other heavy metal citrates. Despite the variety of scientific publications discussing the influence of cadmium on mammalian postnatal development, the effect of this metal on embryogenesis has not yet been sufficiently studied. In this experimental study, cadmium chloride was administered to experimental pregnant female Wistar rats at a daily dose of 1.0 mg/kg. Rats were allocated at random into groups receiving either cadmium chloride alone or additional zinc citrate, cerium citrate, or nanocomposite (based on iodine, sulfur, and selenium citrate). The control group received distilled water at an equivalent volume. In each group, operational intervention occurred at the 13th and 20th day of gestation to assess numbers of live fetuses, corpora lutea, pre-implantation losses, post-implantation losses, and total implantation losses. When cadmium chloride alone was administered, a pronounced embryotoxic effect was observed, manifested as a significant decrease in the number of live fetuses. Experimental groups which received cadmium chloride with zinc citrate, cerium citrate, or nanocomposite had an increased number of live fetuses and corpora lutea, as well as a decreased number of implantation losses, compared to the group which only received cadmium chloride. Each combination of cerium, zinc, and selenium nanocomposite citrates demonstrated a compensatory effect on all measures of embryogenesis impacted by cadmium embryotoxicity. Thus, administration of the citrates of cerium, zinc, and selenium nanocomposite reduces cadmium embryotoxicity and its accumulation in the body.

Clinical applications of photon counting detector CT.

The X-ray detector is a fundamental component of a CT system that determines the image quality and dose efficiency. Until the approval of the first clinical photon-counting-detector (PCD) system in 2021, all clinical CT scanners used scintillating detectors, which do not capture information about individual photons in the two-step detection process. In contrast, PCDs use a one-step process whereby X-ray energy is converted directly into an electrical signal. This preserves information about individual photons such that the numbers of X-ray in different energy ranges can be counted. Primary advantages of PCDs include the absence of electronic noise, improved radiation dose efficiency, increased iodine signal and the ability to use lower doses of iodinated contrast material, and better spatial resolution. PCDs with more than one energy threshold can sort the detected photons into two or more energy bins, making energy-resolved information available for all acquisitions. This allows for material classification or quantitation tasks to be performed in conjunction with high spatial resolution, and in the case of dual-source CT, high pitch, or high temporal resolution acquisitions. Some of the most promising applications of PCD-CT involve imaging of anatomy where exquisite spatial resolution adds clinical value. These include imaging of the inner ear, bones, small blood vessels, heart, and lung. This review describes the clinical benefits observed to date and future directions for this technical advance in CT imaging. KEY POINTS: • Beneficial characteristics of photon-counting detectors include the absence of electronic noise, increased iodine signal-to-noise ratio, improved spatial resolution, and full-time multi-energy imaging. • Promising applications of PCD-CT involve imaging of anatomy where exquisite spatial resolution adds clinical value and applications requiring multi-energy data simultaneous with high spatial and/or temporal resolution. • Future applications of PCD-CT technology may include extremely high spatial resolution tasks, such as the detection of breast micro-calcifications, and quantitative imaging of native tissue types and novel contrast agents.

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.

Exploring Guanidinium Organocatalysts for Hypoiodite-Mediated Reactions.

This account describes our recent work on developing guanidinium hypoiodite- catalysts for oxidative carbon-nitrogen and carbon-carbon bond-forming reactions. These reactions proceeded smoothly using guanidinium hypoiodite generated in situ by treating 1,3,4,6,7-hexahydro-2H-pyrimido[1,2-a]pyrimidine hydroiodide salts with an oxidant. In this approach, the ionic interaction and hydrogen bonding ability of the guanidinium cations enable bond-forming reactions that have been difficult with conventional methods. Enantioselective oxidative carbon-carbon bond-forming reaction was also achieved by using a chiral guanidinium organocatalyst.

Differences in Hypersensitivity Reactions to Iodinated Contrast Media: Analysis of the US Food and Drug Administration Adverse Event Reporting System Database.

BACKGROUND: A comparative hypersensitivity risk profile of frequently used iodinated contrast media (ICM) may be required for their safer use. OBJECTIVE: To explore the association between hypersensitivity reactions (HSRs) and specific ICM and characterize the spectrum of ICM-related HSRs. METHODS: We performed a disproportionality analysis and proportionality test to assess the safety profile of ICM-related HSRs and compare the frequency ratio of specific HSRs in diverse age, sex, and country subgroups. We used reports downloaded from the US Food and Drug Administration Adverse Event Reporting System and data on the national use of individual ICM for this analysis. RESULTS: A total of 11,343,365 adverse event reports were collected from the first quarter of 2013 to the first quarter of 2021, among which 5,432 cases were identified as ICM-induced HSRs. All of the studied ICMs were associated with overreporting frequencies of HSRs, in which iomeprol showed the highest reporting odds ratio (ROR) of 24.75 (95% CI, 19.61-31.24). Iopromide (ROR = 22.29; 95% CI, 20.18-24.62) and ioversol (ROR = 20.85; 95% CI, 18.54-23.44) were more likely to cause angioedema than other ICMs, particularly in the group aged 45 to 64 years. Iomeprol was associated with the largest disproportionality for severe cutaneous adverse reactions (ROR = 127.90; 95% CI, 103.32-159.88), whereas iodixanol exhibited maximal incidence when total use cases were considered. Regarding anaphylactic shock, iopamidol presented the highest disproportionality (ROR = 31.11; 95% CI, 27.15-35.65), especially in males or seniors aged greater than 65 years, whereas iopromide resulted in the maximum frequency in China and the United States. CONCLUSIONS: Different ICMs exhibited diverse profiles regarding HSRs, which could be further affected by age, sex, or geographic area. Prospective studies are required for patient safety.