Background Nephrogenic systemic fibrosis is a fibrosing disorder associated with exposure to gadolinium-based contrast agents in people with severely compromised renal function. Objective The purpose of this study was to determine the reported number of cases of nephrogenic systemic fibrosis in children using three distinct publicly available data sources. Materials and methods We conducted systematic searches of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), the International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) registry and published literature from January 1997 through September 2012. We contacted authors of individual published cases to obtain follow-up data. Data sets were cross-referenced to eliminate duplicate reporting. Results We identified 23 children with nephrogenic systemic fibrosis. Seventeen had documented exposure to gadolinium-based contrast agents. Six children had been reported in both the FAERS and the literature, four in the FAERS and the ICNSFR registry and five in all three data sources. Conclusion Nephrogenic systemic fibrosis has been rarely reported in children. Although rules related to confidentiality limit the ability to reconcile reports, active pharmaco-vigilance using RADAR (Research on Adverse Drug events And Reports) methodology helped in establishing the number of individual pediatric cases within the three major data sources.

Cite this article as: Edwards BJ, Laumann AE, Nardone B, Miller FH, Restaino J, Raisch DW, et al. Advancing pharmacovigilance through academic-legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis-a research on adverse drug events and reports (RADAR) report. Br J Radiol 2014;87:20140307. FULL PAPERAdvancing pharmacovigilance through academic-legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis-a research on adverse drug events and reports (RADAR) report Results: The FAERS encompassed the largest number (n 5 1395) of NSF reports. The ICNSFR contained the most complete (n 5 335, 100%) histopathological data. A total of 382 individual biopsy-proven, product-specific NSF cases were analysed from the legal data set. 76.2% (291/382) identified exposure to gadodiamide, of which 67.7% (197/291) were unconfounded. Additionally, 40.1% (153/382) of cases involved gadopentetate dimeglumine, of which 48.4% (74/153) were unconfounded, while gadoversetamide was identified in 7.3% (28/382) of which 28.6% (8/28) were unconfounded. Some cases involved gadobenate dimeglumine or gadoteridol, 5.8% (22/382), all of which were confounded. The mean number of exposures to gadolinium-based contrast agents (GBCAs) was gadodiamide (3), gadopentetate dimeglumine (5) and gadoversetamide (2). Of the 279 unconfounded cases, all involved a linear-structured GBCA. 205 (73.5%) were a non-ionic GBCA while 74 (26.5%) were an ionic GBCA. Conclusion: Clinical and legal databases exhibit unique characteristics that prove complementary in safety evaluations. Use of the legal data set allowed the identification of the most commonly implicated GBCA. Advances in knowledge: This article is the first to demonstrate explicitly the utility of a legal data set to pharmacovigilance research.

Rationale and Objectives The Food and Drug Administration recommends renal function estimation using laboratory testing for patients at risk for chronically reduced kidney function before the administration of gadolinium-based contrast agents (GBCAs). Point-of-care (POC) estimated glomerular filtration rate (eGFR) testing was added to the pre-magnetic resonance (MR) questionnaire at our institution in June 2008 for all patients undergoing a contrast-enhanced MR exam. This study was done to evaluate the effectiveness of a pre-MR screening questionnaire about kidney disease and to assess POC eGFR detection of additional patients at risk for nephrogenic systemic fibrosis. Materials and Methods This retrospective study was approved by our institutional review board and determined to be Health Insurance Portability and Accountability Act compliant. Medical records, laboratory data, and pre-MR questionnaires of all patients who presented for contrast-enhanced MR scans during October 2008 were reviewed. The National Kidney Disease Education Program isotope-dilution mass spectrometry-traceable Modification of Diet in Renal Disease equation was used to calculate eGFRs using the POC creatinine laboratory value, age, race, and gender. Sensitivity and specificity were calculated using 2 × 2 tables, and 95% confidence intervals were calculated with exact binomial confidence intervals. Results A total of 1167 individuals presented for contrast-enhanced MR scans. Of 13 individuals on dialysis, 2 did not report renal disease. Of 1154 individuals not on dialysis, 25 had an eGFR <30 mL/min/1.73 m2 (95% CI 1.41%–3.18%). Of these 25, 13 did and 12 did not report renal disease. The sensitivity of the questionnaire for identifying patients with an eGFR <30 mL/min/1.73 m2 was 63.2%. POC eGFR estimations identified a prevalence of 2.17% (95% CI: 1.41%–3.18%) of the total individuals not on dialysis, with an eGFR <30 mL/min/1.73 m2. Patients who denied kidney dysfunction had a 1.08% (95% CI: 0.56%–1.88%) posttest probability of having an eGFR <30 mL/min/1.73 m2. Conclusions POC eGFR testing identified a significant number of individuals with renal dysfunction not found by the pre-MR imaging questionnaire alone.

Mucinous carcinoma (also termed colloid carcinoma) of the breast accounts for 1%-6% of all breast cancer and is considered to have a good relative prognosis. The most common mammographic appearance of pure mucinous carcinoma is a high-density mass with circumscribed margins and on sonographic examination an isoechoic round mass with circumscribed margins. We report 2 cases of invasive mucinous carcinoma, in which one patient showed an intermediate recurrence risk based on Ki-67 and human epidermal growth factor receptor 2 negativity, while the other showed a low Ki-67 recurrence risk and human epidermal growth factor receptor 2 positive. We also review the literature on Ki-67 and human epidermal growth factor receptor 2 and explore the roles of these molecular markers in mucinous carcinomas.