Practice parameters for diagnosing and managing iodinated contrast media hypersensitivity.

Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%-3% of patients receiving nonionic ICM. The diagnosis and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re-exposition or drug provocation test should only be done with skin test-negative ICMs. The decision for performing either re-exposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.

Improved identification of DNA double strand breaks: γ-H2AX-epitope visualization by confocal microscopy and 3D reconstructed images.

Currently, in the context of radiology, irradiation-induced and other genotoxic effects are determined by visualizing DSB-induced DNA repair through γ-H2AX immunofluorescence and direct counting of the foci by epifluorescence microscopy. This procedure, however, neglects the 3D nature of the nucleus. The aim of our study was to use confocal microscopy and 3D reconstructed images to improve documentation and analysis of γ-H2AX fluorescence signals after diagnostic examinations. Confluent, non-dividing MRC-5 lung fibroblasts were irradiated in vitro with a Cs-137 source and exposed to radiation doses up to 1000 mGy before fixation and staining with an antibody recognizing the phosphorylated histone variant γ-H2AX. The 3D distribution of γ-H2AX foci was visualized using confocal laser scanning microscopy. 3D reconstruction of the optical slices and γ-H2AX foci counting were performed using Imaris Image Analysis software. In parallel, γ-H2AX foci were counted visually by epifluorescence microscopy. In addition, whole blood was exposed ex vivo to the radiation doses from 200 to 1600 mGy. White blood cells (WBCs) were isolated and stained for γ-H2AX. In fibroblasts, epifluorescence microscopy alone visualized the entirety of fluorescence signals as integral, without correct demarcation of single foci, and at 1000 mGy yielded on average 11.1 foci by manual counting of 2D images in comparison to 36.1 foci with confocal microscopy and 3D reconstruction (p < 0.001). The procedure can also be applied for studies on WBCs. In contrast to epifluorescence microscopy, confocal microscopy and 3D reconstruction enables an improved identification of DSB-induced γ-H2AX foci, allowing for an unbiased, ameliorated quantification.

Monitoring of tumor burden in vivo by optical imaging in a xenograft SCID mouse model: evaluation of two fluorescent proteins of the GFP-superfamily.

BACKGROUND: Mouse models of human-malignant-melanoma (MM) are important tools to study tumor dynamics. The enhanced green fluorescent protein (EGFP) is widely used in molecular imaging approaches, together with optical scanners, and fluorescence imaging. PURPOSE: Currently, there are no data available as to whether other fluorescent proteins are more suitable. The goal of this preclinical study was to analyze two fluorescent proteins of the GFP superfamily under real-time in vivo conditions using fluorescence reflectance imaging (FRI). MATERIAL AND METHODS: The human melanoma cell line MeWo was stable transfected with one plasmid: pEGFP-C1 or pDsRed1-N1. We investigated two severe combined immunodeficiency (SCID)-mice groups: A (solid xenografts) and B (xenografts as metastases). After three weeks, the animals were weekly imaged by FRI. Afterwards the mice were euthanized and metastases were imaged in situ: to quantify the cutis-dependent reduction of emitted light, we compared signal intensities obtained by metastases in vivo with signal intensities obtained by in situ liver parenchyma preparations. RESULTS: More than 90% of cells were stable transfected. EGFP-/DsRed-xenograft tumors had identical growth kinetics. In vivo the emitted light by DsRed tumors/metastases was much brighter than by EGFP. DsRed metastases were earlier (3 vs. 5 weeks) and much more sensitive detectable than EGFP metastases. Cutis-dependent reduction of emitted light was greater in EGFP than in DsRed mice (tenfold). Autofluorescence of DsRed was lower than of EGFP. CONCLUSION: We established an in vivo xenograft mouse model (DsRed-MeWo) that is reliable, reproducible, and superior to the EGFP model as a preclinical tool to study innovative therapies by FRI under real-time in vivo conditions.

Enhancing patient value efficiently: Medical history interviews create patient satisfaction and contribute to an improved quality of radiologic examinations.

Diagnostic radiology examinations are generally very efficient processes optimized for high throughput and for serving the needs of physicians. On the downside, streamlined examinations disrupt the personal relationship between diagnosticians and patients. The radiology associations RSNA and ACR consider low visibility of radiologists a threat to the profession. Therefore, they launched counter-acting initiatives that aim at increasing patient satisfaction by providing more personal attention and care, and by raising knowledge about the discipline. However, they did not formulate concrete instructions on how to integrate care by radiologists into the examination process while inhibiting the flow minimally. From an internal patient satisfaction survey, we have seen that patients rated satisfaction with care and attention by physicians relatively low, indicating that patients would welcome a possibility to communicate with radiologists. In a controlled experimental setting, we have then changed our process to include a short medical history interview. Thereby we could corroborate that lack of educated communication is the primary cause of diminished satisfaction and could establish that the duration of the encounter is not critical to achieving improvement. Importantly, the interview also helped to improve the quality of the examination. Thus, short medical history interviews are a very efficient way to increase value by maximizing patient satisfaction and examination quality. Our approach is easy to implement in other radiology clinics that are interested in becoming more patient-centered and in raising patient satisfaction.

Iodinated Contrast Media and the Alleged "Iodine Allergy": An Inexact Diagnosis Leading to Inferior Radiologic Management and Adverse Drug Reactions.

Purpose To test the hypothesis that the incomplete diagnosis "iodine allergy" is a possibly dangerous concept for patients under routine radiologic conditions. Materials and Methods 300 patients with a history of an "iodine allergy" were retrospectively screened and compared with two age-, sex-, and procedure-matched groups of patients either diagnosed with a nonspecific "iodine contrast medium (ICM) allergy" or an allergy to a specific ICM agent. For all groups, the clinical symptoms of the most recent past adverse drug reaction (ADR), prophylactic actions taken for subsequent imaging, and ultimate outcome were recorded and analyzed. Results The diagnosis "iodine allergy" was not otherwise specified in 84.3 % patients. For this group, in most cases, the symptoms of the previous ADRs were not documented. In contrast, the type of ADR was undocumented in only a minority of patients in the comparison groups. In the group of patients with an "iodine allergy" the percentage of unenhanced CT scans was greater than within the other two groups (36.7 % vs. 28.7 %/18.6 %). ADRs following prophylactic measures were only observed in the "iodine allergy" group (OR of 9.24 95 % CI 1.16 - 73.45; p < 0.04). Conclusion This data confirms the hypothesis that the diagnosis "iodine allergy" is potentially dangerous and results in uncertainty in clinical management and sometimes even ineffective prophylactic measures. Key points · The term "iodine allergy" is imprecise, because it designates allergies against different substance classes, such as disinfectants with complexed iodine and contrast media containing covalently bound iodine.. · There is a clear correlation between the exactness of the diagnosis - from the alleged "iodine allergy" to "contrast media allergy" to naming the exact culprit CM - and the quality of documentation of the symptoms.. · Management of patients diagnosed with "iodine allergy" was associated with uncertainty leading to unenhanced scans and sometimes unnecessary prophylactic actions.. · The term "iodine allergy" should be omitted, because it is potentially dangerous and can decrease the quality of radiology exams.. Citation Format · Böhm Ingrid, Nairz Knud, Morelli John N et al. Iodinated Contrast Media and the Alleged "Iodine Allergy": An Inexact Diagnosis Leading to Inferior Radiologic Management and Adverse Drug Reactions. Fortschr Röntgenstr 2017; 189: 326 - 332.

Myths and misconceptions concerning contrast media-induced anaphylaxis: a narrative review.

Contrast-enhanced radiological examinations are an increasingly important diagnostic tool in modern medicine. All approved and available contrast media (iodinated and gadolinium-based) are safe compounds that are well-tolerated by most patients. However, a small percentage of patients exhibit contrast medium-induced adverse drug reactions that are dose-dependent and predictable (type A) or an even smaller cohort experience so-called type B (dose-independent, non-predictable). To increase patients' safety, recommendations/guidelines have been put forth in the literature and advice passed down informally by radiologists in practice to ensure contrast media safety. Through these, both reasonable suggestions as well as misinterpretations and myths (such as the misleading terms "allergy-like" reactions, and "iodine-allergy", the wrong assumption that the initial contact to a contrast medium could not induce an allergy, the estimation that an anti-allergy premedication could suppress all possible adverse reactions, and interleukin-2 as a risk/trigger for contrast medium adverse events) have arisen. Since the latter are not only unhelpful but also potentially reduce patients' safety, such myths and misconceptions are the focus of this review.

Contrast agents and ionization with respect to safety for patients and doctors.

In hemodialysis patients, radiographic imaging with iodinated contrast medium (ICM) application plays a central role in the diagnosis and/or follow-up of disease-related conditions. Therefore, safety aspects concerning ICM administration and radiation exposure have a great impact on this group of patients. Current hardware and software improvements including the design and synthesis of modern contrast compounds allow the use of very small amounts of ICM in concert with low radiation exposure. Undesirable ICM side effects are divided into type A (predictable reactions such as heat feeling, headache, and contrast-induced acute kidney injury, for example) and type B (nonpredictable or hypersensitivity) reactions; this chapter deals with the latter. The first onset cannot be prevented. To prevent hypersensitivity upon reexposure of ICM, an allergological workup is recommended. If this is not possible and ICM is necessary, the patient should receive a premedication (H1 antihistamine with or without corticosteroids). Current imaging hardware and software improvements (e.g. such as additional filtration of the X-ray beam) allow the use of very small amount of ICM and small X-ray doses. Proper communication among the team involved in the treatment of a patient may allow to apply imaging protocols and efficient imaging strategies limiting radiation exposure to a minimum. Practical recommendations will guide the reader how to use radiation and ICM efficiently to improve both patient and staff safety.

Classification of acute and delayed contrast media-induced reactions: proposal of a three-step system.

Physicians and scientists use a broad spectrum of terms to classify contrast media (CM)-induced adverse reactions. In particular, the designation of hypersensitivity reactions is quite varied. Consequently, comparisons of different papers dealing with this subject are difficult or even impossible. Moreover, general descriptions may lead to problems in understanding reactions in patients with a history of adverse CM-reactions, and in efficiently managing these patients. Therefore, the goal of this paper is to suggest an easy system to clearly classify these reactions. The proposed three-step systems (3SS) is built up as follows: step 1 exactly describes the clinical features, including their severity; step 2 categorizes the time point of the onset (immediate or nonimmediate); and step 3 generally classifies the reaction (hypersensitivity or nonhypersensitivity reaction). The 3SS may facilitate better understanding of the clinical manifestations of adverse CM reactions and may support the prevention of these reactions on the basis of personalized medicine approaches.

Biological applications of magnetic nanoparticles.

In this review an overview about biological applications of magnetic colloidal nanoparticles will be given, which comprises their synthesis, characterization, and in vitro and in vivo applications. The potential future role of magnetic nanoparticles compared to other functional nanoparticles will be discussed by highlighting the possibility of integration with other nanostructures and with existing biotechnology as well as by pointing out the specific properties of magnetic colloids. Current limitations in the fabrication process and issues related with the outcome of the particles in the body will be also pointed out in order to address the remaining challenges for an extended application of magnetic nanoparticles in medicine.