Tens of millions of contrast-enhanced magnetic resonance imaging (MRI) exams are performed annually around the world. The contrast agents, which improve diagnostic accuracy, are almost exclusively small, hydrophilic gadolinium(III) based chelates. In recent years concerns have arisen surrounding the long-term safety of these compounds, and this has spurred research into alternatives. There has also been a push to develop new molecularly targeted contrast agents or agents that can sense pathological changes in the local environment. This comprehensive review describes the state of the art of clinically approved contrast agents, their mechanism of action, and factors influencing their safety. From there we describe different mechanisms of generating MR image contrast such as relaxation, chemical exchange saturation transfer, and direct detection and the types of molecules that are effective for these purposes. Next we describe efforts to make safer contrast agents either by increasing relaxivity, increasing resistance to metal ion release, or by moving to gadolinium(III)-free alternatives. Finally we survey approaches to make contrast agents more specific for pathology either by direct biochemical targeting or by the design of responsive or activatable contrast agents.

Chemistry of MRI Contrast Agents: Current Challenges and New Frontiers

In vivo imaging, which enables us to peer deeply within living subjects, is producing tremendous opportunities both for clinical diagnostics and as a research tool. Contrast material is often required to clearly visualize the functional architecture of physiological structures. Recent advances in nanomaterials are becoming pivotal to generate the high-resolution, high-contrast images needed for accurate, precision diagnostics. Nanomaterials are playing major roles in imaging by delivering large imaging payloads, yielding improved sensitivity, multiplexing capacity, and modularity of design. Indeed, for several imaging modalities, nanomaterials are now not simply ancillary contrast entities, but are instead the original and sole source of image signal that make possible the modality’s existence. We address the physicochemical makeup/design of nanomaterials through the lens of the physical properties that produce contrast signal for the cognate imaging modality—we stratify nanomaterials on the basis of thei...

Nanomaterials for In Vivo Imaging

Anaphylaxis

This pharmacoepidemiology study uses national Canadian electronic medical record data to describe treatment indications for antidepressants and temporal trends in antidepressant prescribing for depression in Quebec, Canada, from 2006 through 2015.

https://jamanetwork.com/journals/jama/articlepdf/2524175/jld160010.pdf

Treatment Indications for Antidepressants Prescribed in Primary Care in Quebec, Canada, 2006-2015

Anemia is a complication that affects a majority of individuals with advanced CKD. Although relative deficiency of erythropoietin production is the major driver of anemia in CKD, iron deficiency stands out among the mechanisms contributing to the impaired erythropoiesis in the setting of reduced kidney function. Iron deficiency plays a significant role in anemia in CKD. This may be due to a true paucity of iron stores (absolute iron deficiency) or a relative (functional) deficiency which prevents the use of available iron stores. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood losses, impaired iron absorption, and chronic inflammation. The traditional biomarkers used for the diagnosis of iron-deficiency anemia (IDA) in patients with CKD have limitations, leading to persistent challenges in the detection and monitoring of IDA in these patients. Here, we review the pathophysiology and available diagnostic tests for IDA in CKD, we discuss the literature that has informed the current practice guidelines for the treatment of IDA in CKD, and we summarize the available oral and intravenous (IV) iron formulations for the treatment of IDA in CKD. Two important issues are addressed, including the potential risks of a more liberal approach to iron supplementation as well as the potential risks and benefits of IV versus oral iron supplementation in patients with CKD.

Iron Deficiency in Chronic Kidney Disease: Updates on Pathophysiology, Diagnosis, and Treatment.

Importance All intravenous (IV) iron products are associated with anaphylaxis, but the comparative safety of each product has not been well established. Objective To compare the risk of anaphylaxis among marketed IV iron products. Design, Setting, and Participants Retrospective new user cohort study of IV iron recipients (n = 688 183) enrolled in the US fee-for-service Medicare program from January 2003 to December 2013. Analyses involving ferumoxytol were limited to the period January 2010 to December 2013. Exposures Administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol as reported in outpatient Medicare claims data. Main Outcomes and Measures Anaphylaxis was identified using a prespecified and validated algorithm defined with standard diagnosis and procedure codes and applied to both inpatient and outpatient Medicare claims. The absolute and relative risks of anaphylaxis were estimated, adjusting for imbalances among treatment groups. Results A total of 274 anaphylaxis cases were identified at first exposure, with an additional 170 incident anaphylaxis cases identified during subsequent IV iron administrations. The risk for anaphylaxis at first exposure was 68 per 100 000 persons for iron dextran (95% CI, 57.8-78.7 per 100 000) and 24 per 100 000 persons for all nondextran IV iron products combined (iron sucrose, gluconate, and ferumoxytol) (95% CI, 20.0-29.5 per 100 000) , with an adjusted odds ratio (OR) of 2.6 (95% CI, 2.0-3.3; P Conclusions and Relevance Among patients in the US Medicare nondialysis population with first exposure to IV iron, the risk of anaphylaxis was highest for iron dextran and lowest for iron sucrose.

/pdf/comparative-risk-of-anaphylactic-reactions-associated-with-8930ydpml4.pdf

Diqiong Xie

Papers

Comparative Risk of Anaphylactic Reactions Associated With Intravenous Iron Products