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The current COVID-19 climate has caused an unforeseen supply shortage of iodinated contrast media (ICM) worldwide, disrupting global distribution.1 In addition, the scarcity has resulted in a ripple effect in healthcare facilities such as radiology departments where ICM is required to perform contrast-enhanced examinations. ICM plays a significant part in contrast-enhanced CT, angiography and fluoroscopic procedures within the radiology department, holding a primary role in the differentiation and diagnosis of pathologies which range from pulmonary emboli to tumours.1 Its use extends beyond radiology, where ICM is heavily relied on in cardiology, urology and gastrointestinal studies, further highlighting the heavy dependence on the critical agent.2 With the global increase in the number of CT examinations requested, where approximately 60% of studies require ICM, optimal usage of ICM must be considered to meet heightened demand.3 The shortage has represented an opportunity for imaging providers to re-examine current imaging protocols and identify whether non-contrast imaging, alternative contrast agents and other imaging modalities could be viable options moving forward.1,2 Additionally, current literature has discussed volume-reduction strategies and dual-energy use in newer-generation CT scanners to conserve ICM.1,4 This review will explore currently proposed solutions that can be implemented in the radiology department to maximise ICM supply with minimal impact on patient care.
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Case report Trometamol (tromethamine, tris(hydroxymethyl)aminomethane (TRIS)) is an excipient frequently used as buffer in fluids and semisolid agents, including many drugs such as antibiotics, iodinated contrast agents and the COVID-19 vaccine mRNA-1273. Here, we report the first case of a delayed-type hypersensitivity after oral intake of trometamol. A 64-year- old female patient presented to our emergency department with generalized erythematous rash, pruritus and swelling of the face five hours after the intake of one tablet of fosfomycin trometamol for a urinary tract infection. Further medical history revealed a previous erythematous rash five to six hours after administration of the iodinated contrast agent iopromide. We performed skin prick and intradermal tests with trometamol, fosfomycin trometamol and various iodinated contrast agents, including iopromide, iomeprol, iobitridol, iopamidol and iodixanol. These tests showed no reactions initially. However, 48 hours after intradermal testing, macular erythematous lesions developed at the sites tested with trometamol 0.1%, trometamol 0.01% and all sites tested with iodinated contrast agents. Furthermore, when we performed a lymphocyte transformation test with trometamol, fosfomycin trometamol and iopromide, we recorded a positive reaction with cytokine release after stimulating T cells with trometamol and iopromide. In contrast, basophil activation testing showed a negative result for these agents. Based on these results and our patient's history, we diagnosed a clinically relevant type IV sensitization to trometamol. There are only a few case reports about immediate-type allergic reactions to gadolinium contrast agents caused by the excipient trometamol. There are some published cases which report contact dermatitis after topical administration of trometamol-containing agents. To our knowledge, ours is the first case to report a delayed hypersensitivity reaction to oral administration of trometamol. Excipients are indispensable for drugs, vaccines and other products since they stabilize and preserve the active agents. Nevertheless, excipients should always be considered during an allergy workup, especially if the patient reports prior drug reactions that cannot be explained by a chemical cross-reaction. In our case, we diagnosed delayed-type hypersensitivity to the excipient trometamol. This is a consequential diagnosis for the patient, because trometamol is contained in many drugs and in the COVID-19 vaccine mRNA-1273.
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Introduction (contexte de la recherche): IgE-mediated reactions to systemic corticosteroids (CSs) are rare. Hydrocortisone and methylprednisolone succinate ester are the most frequent elicitors. Excipients of depot corticosteroids (like carmellose or macrogol) may also be involved. The involvement of the dipropionate form of betamethasone (present in the depot Diprostene) has not been studied. Objectif: To describe the case of a 40-year-old woman, who presented an anaphylactic shock reaction upon intra-articular administration of Diprostene (Betamethasone sodium phosphate and betamethasone dipropionate), associated with an iodinated radiocontrast media (ICM, Xenetix). Methodes: An allergy work-up was performed, according to recommendations for severe immediate reactions. Nine months after the reaction [hypotension (7/5 mmHg), erythema and desaturation at 94%, treated with adrenalin, methylprednisolone hemisuccinate, dexchlorpheniramine] the patient underwent skin prick tests (SPT) and intradermal tests (IDT) with ICM, bethamethasone and Diprostene (commercial molecules). Latex and chlorexidine were also studied. Resultats: The tests resulted negative for ICM, latex and chlorexidine (including serum specific IgE ImmunoCAP ThermoFisher Scientific), bethametasone phosphate (IDT 0.4 mg/mL) and carmellose (IDT 0.5 mg/mL). SPT elicited a positive reaction towards Diprostene in immediate reading, (for 5, 0.5, 0.05 mg/mL) with an erythema (10, 8, 5 mm respectively) and a wheal (of at least 3 mm for each SPT). We performed an oral drug challenge to bethametasone phosphate for a total of 8 mg and it was well tolerated. The basal tryptase was 5.5 microg/mL. Tryptasemia 30 minutes after the reaction was 26.8 microg/mL. Conclusion(s): We describe an anaphylactic reaction to Diprostene, proven by positive ST. The hypothesis of allergy to betamethasone dipropionate is under investigation. The hypothesis of allergy to macrogol, the other excipient of (which was not tested separately) is less likely, since the patient received Commirnaty SARS-CoV-2 vaccine 3 months after the reaction. The allergy work-up is ongoing (tests are programmed for betamethasone dipropionate alone).Copyright © 2023
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Case report The first approved COVID-19 vaccines include BNT162B2 Pfizer-BioNTech and mRNA-1273 Moderna mRNA vaccines. Some severe allergic reactions to these vaccines have been report, and even though there is a lack of robust evidence, IgE-mediated hypersensitivity to excipients may be the cause of several. The excipient polyethylene glycol (PEG) is present in both, whilst Moderna further contains trometamol (or tromethamine), a buffer additive present in drug formulations and contrast media. We report the case of a 40 year-old woman, with controlled allergic rhinitis and asthma, who was referred to our Immunoallergology Department due to an anaphylactic reaction to Moderna COVID-19 vaccine. She described an episode of cervical and facial pruritus 5 minutes after receiving the first dose of vaccine, which rapidly evolved to generalized urticaria. She was promptly given intravenous (IV) clemastine with improvement of symptoms. However, 1h later she developed respiratory symptoms (dry cough, shortness of breath and wheezing). IV hydrocortisone was also given, and the patient was kept under medical supervision for 6h, after which she was discharged home. The following day, she had urticaria that resolved with oral deflazacort (60 mg). She denies exercise practice, alcohol consumption or outset of new drugs prior to vaccination. During investigation, the patient described two similar reactions in the past, 5 minutes after the administration of trometamol-containing contrast media (10 years before with an iodinated contrast and 2 years ago with a gadolinium contrast, both with trometamol). A week after the reaction all laboratory evaluation were within normal limits, including tryptase level. Skin tests were performed, 2 months after, with contrast media that contain trometamol (iopromide, iomeprol, iodixanol, ioversol, gadobutrol) and that do not (ioxitalamate, amidotrizoate, gadoterate meglumine), in accordance with the EAACI/ENDA guidelines. Iopromide and iodixanol were positive on intradermal testing (1:10 dilution), suggesting trometamol as the culprit excipient. She was advised not to receive the 2nd dose of Moderna vaccine. She received Pfizer-BioNTech vaccine at the hospital, without any reactions. This case demonstrates that an IgE-mediated reaction to trometamol may be an underlying mechanism for immediate hypersensitivity to mRNA Moderna vaccine. The risk of an allergic reaction to it increases when a previous history of hypersensitivity to contrast media exists.
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Introduction: The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a novel enveloped RNA beta-coronavirus responsible for the Coronavirus disease-19 (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. The SARS-CoV-2 pandemic has spread rapidly worldwide. Few cases and case series have been published reporting COVID-19 related subacute thyroiditis. We report a case of COVID-19 related thyroiditis. Case Description: 73-year-old female presented to the hospital with complaint of shortness of breath, fever and weakness. She was diagnosed with COVID-19 pneumonia and treated with dexamethasone and convalescent plasma. Patient was discharged home after 10 days. Two days after discharge, she presented with complaint of generalized weakness. She was noted to have thyrotoxicosis. Patient was not taking lithium or amiodarone and she did not receive iodinated contrast. She had no sign or symptoms of thyrotoxicosis. She denied neck pain or difficulty swallowing. On laboratory evaluation, SARS Coronavirus 2 RNA was positive. RSV, Influenza A and Influenza B by PCR were negative. TSH was low at 0.182 uIU/mL (0.450-5.330 uIU/mL), free T4 elevated at 3.00 ng/dL (0.58-1.64 ng/dL), free T3 elevated at 5.24 pg/mL (2.20-4.10 pg/mL). Her TSH 3 weeks ago was normal at 0.723 uIU/mL. Thyroid stimulating immunoglobulin negative < 0.10 (< =0.54 IU/L). Thyroid ultrasound showed normal sized gland, few sub centimeter nodules bilaterally. NM thyroid uptake and scan showed low uptake and no focal hot or cold nodule. Her workup was consistent with thyroiditis. Correlating with the diagnosis of COVID-19, this could be most likely COVID-19 related thyroiditis. Repeat labs in a week showed normal TSH 1.138 uIU/mL, normal free T4 1.28 ng/dL and low free T3 1.93 pg/mL. The patient likely had thyroiditis during early course of COVID-19 infection and was caught during the late phase and hence, improvement of thyroid function within a week of biochemical diagnosis. Discussion: Subacute thyroiditis is a self-limited inflammatory disorder, characterized by neck pain, general symptoms and thyroid dysfunction. It has been linked to viral infection like mumps virus, coxsackievirus, adenovirus, Epstein-Barr virus, rubella and cytomegalovirus. In our patient, SARS-CoV-2 was the likely cause of thyroiditis. A single center retrospective study done in 287 patients hospitalized with COVID-19 in Milan, Italy reported 20% of patients with thyrotoxicosis, 5% with hypothyroidism and 74% with normal thyroid function test. We report this case to alert clinicians that thyroiditis and resultant thyrotoxicosis should always be considered as a differential diagnosis in patients with COVID-19.
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The efficient regioselective bromination and iodination of the nonsteroidal anti-inflammatory drug (NSAID) carprofen were achieved by using bromine and iodine monochloride in glacial acetic acid. The novel halogenated carprofen derivatives were functionalized at the carboxylic group by esterification. The regioselectivity of the halogenation reaction was evidenced by NMR spectroscopy and confirmed by X-ray analysis. The compounds were screened for their in vitro antibacterial activity against planktonic cells and also for their anti-biofilm effect, using Gram-positive bacteria (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). The cytotoxic activity of the novel compounds was tested against HeLa cells. The pharmacokinetic and pharmacodynamic profiles of carprofen derivatives, as well as their toxicity, were established by in silico analyses.
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Background: Large vessel occlusion (LVO) is the most common stroke subtype for those patient's presenting with COVID-19. Clot perviousness, or a clot's permeability to iodinated contrast, provides insight to an individual's responsiveness of hyperacute revascularization, clot origin and functional post-stroke outcomes. We aimed to calculate LVO perviousness for those with and without COVID-19 and its association with revascularization and outcomes. Methods: This is a retrospective case-control study for individuals presenting with middle cerebral artery (MCA) LVO with and without COVID-19 positivity. Clot perviousness was calculated by a blinded experienced neuroradiologist. Perviousness scores were compared with demographic and comorbidity information as well as revascularization and functional outcomes. Results: 18 individuals with a MCA LVO (9 COVID-19 infected) were included. Those with COVID-19 were significantly more likely to have diabetes mellitus [67% (6/9) versus 11% (1/9), p = 0.05] and hypertension [89% (8/9) versus 22% (2/9), p = 0.02]. Clot perviousness trended lower in the COVID-19 group [11.0 (8.2 - 26.4) versus 31.7 (30.4 - 39.2), p = 0.10]. Those with COVID-19 infection tended to have a lower clot pervious score, [22% (2/9) versus 78% (7/9), p =0.057]. The majority of those presenting with COVID-19 died during the hospitalization. Conclusions: Our data suggests for those with COVID-19 and MCA LVO, clots tended to be more impermeable to iodinated contrast. This finding may be due to the underlying coagulopathy of COVID-19, namely alternations in fibrin homeostasis. (Figure Presented).
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Introduction: Double-positive vasculitis with anti-polynuclear cytoplasm (ANCA) and anti-glomerular basement membrane (GBM) antibodies is a rare entity of systemic vasculitis defined by the presence of ANCA and anti-GBM antibodies. Methods: We report a rare case of pulmonary-renal syndrome with atypical clinical presentation. Results: A 52 year-old smoking man with a history of exposure to hydrocarbons and uretheral lithiasis, presented in April 2021 epigastralgia and vomiting. the investigations concluded to H.pylori gastritis and ulcer and he received a quadruple therapy. The kidney function was correct in April 2021. The evolution was marked by the persistence of symptoms and urine output had decreased for a few days. He was found to have renal dysfunction (serum creatinine: 2000 µmol/L). Abdominal CT scan without iodinated contrast injection showed severe hydronephrosis of the right pelvicalyceal system with cortical thinning and dilatation of the right ureter. The two kidneys had regular outlines seat multiple bilateral renal cysts with exophytic development. He had a nephrosomy with secondarily a right double-J stent with slight improvement of renal function. The patient presented then with acute respiratory distress.Testing for COVID-19: PCR and serology were negatives. Chest CT scan showed alveolar syndromeevoking pulmonary overload. No pneumopathy covid was shown. The evolution was marked by the non improvement by depletion and he developed hemoptic sputum and low-abundance epistaxis. The attitude was non-invasive ventilation and broad-spectrum antibiotics therapy. Control chest CT showed emphysematous lung with signs of fibrosis with bilateral subpleural nodules. A rereading of the scanner showed intraalveolar hemorrhage which has regressed on the imaging of the control. Based on these data, pneumo renal syndrome was suspected and a bronchoscopy was performed showing alveolar hemorrhage with 70% siderophageswith Gold score superior to 100. Anti-GBM and p-ANCA and antibodies were positive at a high titer. Electroneuromyogram was without anomaly. Kidney biopsy was not done because of the presence of multiple cysts. The patient received pulse methylprednisone for three days followed by oral prednisone and underwent eleven sessions of plasmapheresis. Intraveinous Cyclophosphamide has been started. He showed remarkable recovery as his lung fields cleared with negativity of GBM antibodies. Kidney function didn't improved and he remained dependent on dialysis. Conclusions: Our observation is exceptional since the clinical and radiological presentation of the patient was not that of a pulmonary-renal syndrome. The elements of this syndrome have in fact been masked by the obstacle on the urinary tract on one hand and the hypothesis of a covid19 pneumonia on the other hand in the face of the epidemiological context. Atypical feature of pulmonary renal syndrome should be kept in mind to avoid diagnostic and treatment delays. No conflict of interest