OBJECTIVE: Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children\'s neurodevelopment compared with exposure to water-based alternatives?
CONCLUSIONS: Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives.
BACKGROUND: HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women\'s iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG.
METHODS: This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228).
METHODS: The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups.
RESULTS: School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant.
CONCLUSIONS: The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG.
CONCLUSIONS: This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine.
BACKGROUND: The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People\'s Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest.
BACKGROUND: NCT05168228.

UNASSIGNED: Excessive iodine intake triggers the Wolff-Chaikoff effect resulting in downregulation of thyroid hormone synthesis to prevent hyperthyroidism. Failure to escape the Wolff-Chaikoff effect can be seen especially in (premature born) infants and may result in prolonged iodine induced hypothyroidism. We describe a rare case of a preterm infant who developed severe iodinated contrast induced hypothyroidism after the use and prolonged stasis of enteral iodinated contrast media (ICM). In addition a systematic literature search was performed to evaluate all available data on this complication.
UNASSIGNED: A systematic literature search was performed in PubMed and Embase. Studies describing the effect of enteral ICM on thyroid function were considered eligible. The primary outcome was to determine the frequency of contrast induced hypothyroidism in infants after administration of enteral ICM.
UNASSIGNED: The premature infant in our center developed severe iodinated contrast induced hypothyroidism after enteral ICM. In total, only two studies met our eligibility data, reporting eight patients. Out of these eight patients, four premature infants developed a contrast induced hypothyroidism after enteral administration of ICM.
UNASSIGNED: Data on severity, length and frequency of contrast induced hypothyroidism after exposure to enteral ICM is very scarce. The herein reported case and literature search illustrate the potential severity of the complication and underline the necessity of future studies on this topic. We recommend standardized monitoring of thyroid function after exposure to enteral ICM in newborns to prevent delayed diagnosis of severe contrast induced hypothyroidism until evidence based recommendations can be made.

BACKGROUND: Two-dimensional (2D) classifications of iodinated contrast media (ICM) are insufficient to explain the observed skin test (ST) reactivity patterns in patients with drug hypersensitivity reactions (DHRs) to ICM.
OBJECTIVE: To refine the current view on allergic DHRs to ICM by analyzing ST reactivity patterns in patients with previous reactions to ICM.
METHODS: Patients with a history of DHR to ICM and positive STs, who presented at the University Hospital of Montpellier between 2004 and 2022, were included in the study. The relative difference between every two ICM products was measured by Manhattan distance and odds ratios were computed for all pairs of products in the immediate reaction (IR) and non-immediate reaction (NIR) ST groups.
RESULTS: A total of 181 patients were included in the study. Odds ratio analysis identified significant associations between classical cross-reactive ICM, such as iohexol-ioversol, iohexol-iomeprol, iomeprol-ioversol, and iohexol-iodixanol in the IR ST group and iohexol-ioversol, iopromide-iohexol, and iomeprol-ioversol in the NIR ST group. We also identified uncommon associations, such as ioxitalamate-amidotrizoate in the IR ST group and amidotrizoate-iopamidol and amidotrizoate-ioxitalamate in the NIR ST group. The results were reflected by the Manhattan distance, which suggested the existence of clusters containing the same classically associated ICM as well as uncommon associations, which we hypothesize to be related to similarities in the 3D structure of the respective ICM.
CONCLUSIONS: Current chemical (2D) classifications cannot explain all observed ST reactivity patterns. Whether the 3D structure can be integrated into the current classifications to interpret the observed ST reactivity patterns and predict tolerance to alternative ICM requires further research.

OBJECTIVE: This study aimed to evaluate the Pharmacovigilance (PV) and severity of hypersensitivity reactions induced by non-ionic Iodinated Contrast Media (ICM) in the radiology diagnosis reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS).
METHODS: We retrospectively reviewed the reports of ICM-induced hypersensitivity reactions submitted to the FAERS database between January 2015 and January 2023 and conducted a disproportionality analysis. The seven most common non-ionic ICM, including iohexol, iopamidol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, were chiefly analyzed. Our primary endpoint was the PV of non-ionic ICM-induced total hypersensitivity events. STATA 17.0 MP was used for statistical analysis.
RESULTS: In total, 35357 reports of adverse reaction events in radiology diagnosis were retrieved from the FAERS database. Among them, 6181 reports were on hypersensitivity reaction events (mean age: 57.1 ± 17.8 years). The hypersensitivity reaction-related PV signal was detected for iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, but not for iopamidol. The proportion of iomeprol-induced hypersensitivity reactions and the probability of ioversol-induced severe hypersensitivity reactions have been found to be significantly increased.
CONCLUSIONS: The probability and severity of hypersensitivity reaction events in non-ionic ICM are different. Iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol have higher risks compared to iopamidol. In addition, the constituent ratio of hypersensitivity reactions induced by iomeprol is significantly increased, and the associated probability induced by ioversol is significantly increased.

Urban rivers are exposed to an increasing load of organic micropollutants from wastewater effluent posing an ecological as well as public health hazard. One-off surveys can capture a snapshot of the pollution profile but fail to reveal the full scale of spatial and temporal heterogeneity. In the present study, 41 micropollutants (non-steroid anti-inflammatory drugs (NSAID), antihypertensives, antiepileptic, antidiabetic, antibiotics, iodinated contrast media (ICM), corrosion inhibitors, pesticides) were monitored every two weeks for one-year upstream and downstream of the Budapest metropolitan area in Danube River (336 samples total). ICMs, benzotriazoles and metamizole degradation products were detected in highest concentration regularly exceeding 100 ng/L. Median concentration of other pharmaceuticals ranged from <1 to 26 ng/L, while pesticides were typically below 10 ng/L. Variability of micropollutant concentration was primarily temporal, exhibiting two different patterns: (1) inverse correlation to river discharge, observed for corrosion inhibitors and carbamazepine (r = -0.505 to -0.665) or (2) inverse correlation to water temperature, observed primarily for ICMs, antihypertensives and antibiotics, r = -0.654 to -0.904). Temperature dependence was also significant after correcting for river discharge. Relative increase of pharmaceuticals was 2-134% after the metropolitan area, partially explained by emission estimates calculated from retail data and metabolization rates. The concentration of five ICMs (iopamidol in 100, iodixanol in 96, diatrizoate in 22, iomeprol in 21 and iohexol 13% of the samples) and two NSAIDs (ibuprofen and diclofenac (in 31.5 and 23% of the samples) exceeded the predicted no environmental effect concentration, posing a risk to algae (HQ = 1.2-6) and fish (HQ = 1.4-1.9), respectively. Results suggest that risk-based monitoring and risk management efforts should focus on ICMs, NSAIDs and industrial chemicals, taking into account that sampling in cold periods and during low flow provides the worst-case estimates.

UNASSIGNED: In collaboration with the Department of Rheumatology, Allergy and Immunology, our study aims to review the outcomes of and propose an improved workflow for the management of patients with prior hypersensitivity reactions to iodinated contrast media (ICM).
UNASSIGNED: Outpatients coming for contrast-enhanced computed tomography (CECT) were stratified into 3 categories (definite, unconfirmed and inaccurate) based on likelihood of their contrast hypersensitivity label. Patients could be offered a different ICM, receive the same ICM, or be referred to an allergist for further evaluation. There were 4 outcomes: (1) alternative ICM tolerated; (2) same ICM tolerated again; (3) patient developed a hypersensitivity reaction to either alternative or original ICM; and (4) CECT was deferred until assessment by an allergist. Comparison was made pre- and post-intervention to see if patient outcomes were improved.
UNASSIGNED: There were 132 patients who made a total of 154 visits (90.3% had documented contrast hypersensitivity). Post-intervention, the number of visits postponed for premedication decreased (81.0% to 34.7%). There was a reduction in hypersensitivity reactions (from 42.9% to 14.3%). Of the 12 patients assessed by the allergist, 6 could continue using the same or alternative ICM, 4 were advised to abstain from further contrast administration and 2 were pending testing with a third agent.
UNASSIGNED: Active intervention by the radiologist can decrease the number of postponed, converted or cancelled CECT studies as well as reduce the number of adverse allergic-like events. Direct collaboration between radiologist and allergist for specific cases may be helpful in patients who will likely need future/repeated CECTs.

The study aims at assessing the potential of graphene-based adsorbents to reduce environmental impacts of Iodinated Contrast Media Agents (ICMs). We analyze an extensive collection of ICMs. A modeling approach resting on molecular docking and Density Functional Theory simulations is employed to examine the adsorption process at the molecular level. The study also relies on a Quantitative Structure-Activity Relationship (QSAR) modeling framework to correlate molecular properties with the adsorption energy (Ead) of ICMs, thus enabling identification of the key mechanisms underpinning adsorption and of the key factors contributing to it. A collection of distinct QSAR-based models is developed upon relying on Multiple Linear Regression and a standard genetic algorithm method. Having at our disposal multiple models enables us to take into account the uncertainty associated with model formulation. Maximum Likelihood and formal model identification/discrimination criteria (such as Bayesian and/or information theoretic criteria) are then employed to complement the traditional QSAR modeling phase. This has the advantage of (a) providing a rigorous ranking of the alternative models included in the selected set and (b) quantifying the relative degree of likelihood of each of these models through a weight or posterior probability. The resulting workflow of analysis enables one to seamlessly embed DFT and QSAR studies within a theoretical framework of analysis that explicitly takes into account model and parameter uncertainty. Our results suggest that graphene-based surfaces constitute a promising adsorbent for ICMs removal, π-π stacking being the primary mechanism behind ICM adsorption. Furthermore, our findings offer valuable insights into the potential of graphene-based adsorbent materials for effectively removing ICMs from water systems. They contribute to ascertain the significance of various factors (such as, e.g., the distribution of atomic van der Waals volumes, overall molecular complexity, the presence and arrangement of Iodine atoms, and the presence of polar functional groups) on the adsorption process.

UNASSIGNED: Hypersensitivity reactions to iodinated contrast media (ICM) are frequently encountered in clinical practice. Severe manifestations, despite being infrequent, can be life-threatening and represent an issue when re-administration of ICM is required. Clear recommendations on prevention and management of relapses are still lacking.
UNASSIGNED: We present the cases of two patients presenting with acute coronary syndrome requiring urgent coronary angiography, with an anamnesis of ICM-induced drug reaction with eosinophilia and systemic symptoms syndrome. Both patients safely underwent a coronary angiography with the use of a different ICM (iobitridol) to the one linked to hypersensitivity manifestations, after premedication with corticosteroids and H1 antagonists.
UNASSIGNED: Our experience highlights that in clinical situations in which the use of ICM is urgently needed, premedication with corticosteroids and H1 antagonists together with the choice of an alternative contrast agent (when the culprit is known) represents an effective strategy to perform a potentially life-saving procedure while avoiding serious systemic allergic reactions.

The COVID-19 pandemic led to disruptions in iodinated contrast media (ICM) production and produced a global product shortage in the spring of 2022. The ACIST CVi system is an automated contrast injector system approved by the FDA for multi-patient dosing of ICM from a single container. A transition from the traditional manifold system for contrast injection to the ACIST CVi automated injector system in our cardiac angiographic labs during the COVID-19 pandemic led to reductions in contrast waste and cost while limiting patient exposure to ICM.

Risk stratification in drug allergy implies that specific risk categories (eg, low, moderate, and high) classify historical drug hypersensitivity reactions. These risk categories can be based on reaction phenotypic characteristics, the timing of the reaction and evaluation, the required reaction management, and individual characteristics. Although a multitude of frameworks have been described in the literature, particularly for penicillin allergy labels, there has yet to be a global consensus, and approaches continue to vary between allergy centers. Immune-mediated drug allergies can sometimes be confirmed using skin testing, but a negative drug challenge is required to demonstrate tolerance and remove the allergy from the electronic health record (\"delabel\" the allergy). Even for quintessential IgE-mediated drug allergy, penicillin allergy, recent data reveal that a direct oral challenge, without prior skin testing, is an appropriate diagnostic strategy in those who are considered low-risk. Drug allergy pathogenesis and clinical manifestations may vary depending on the culprit drug, and as such, the optimal approach should be based on risk stratification that considers individual patient and reaction characteristics, the likely hypersensitivity reaction phenotype, the drug class, and the patient\'s clinical needs. This article will describe low-risk drug allergy labels, focusing on β-lactam and sulfonamide antibiotics, nonsteroidal anti-inflammatory drugs, iodinated contrast media, and common chemotherapeutics. This review will also address practical management approaches using currently available risk stratification and clinical decision tools.