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

On October 20, 2017, Zoster Vaccine Recombinant, Adjuvanted (Shingrix, GlaxoSmithKline, [GSK] Research Triangle Park, North Carolina), a 2-dose, subunit vaccine containing recombinant glycoprotein E in combination with a novel adjuvant (AS01B), was approved by the Food and Drug Administration for the prevention of herpes zoster in adults aged ≥50 years. The vaccine consists of 2 doses (0.5 mL each), administered intramuscularly, 2-6 months apart (1). On October 25, 2017, the Advisory Committee on Immunization Practices (ACIP) recommended the recombinant zoster vaccine (RZV) for use in immunocompetent adults aged ≥50 years.

/pdf/recommendations-of-the-advisory-committee-on-immunization-2giwxi28x0.pdf

Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines

https://usiena-air.unisi.it/bitstream/11365/1064413/2/Vaccination%20in%20the%20elderly.pdf

Vaccination in the elderly: The challenge of immune changes with aging.

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

Comparative Risk of Anaphylactic Reactions Associated With Intravenous Iron Products

Background Tens of millions of seniors are at risk of herpes zoster (HZ) and its complications. Live attenuated herpes zoster vaccine (HZV) reduces that risk, although questions regarding effectiveness and durability of protection in routine clinical practice remain. We used Medicare data to investigate HZV effectiveness (VE) and its durability. Methods This retrospective cohort study included beneficiaries ages ≥65 years during January 2007 through July 2014. Multiple adjustments to account for potential bias were made. HZV-vaccinated beneficiaries were matched to unvaccinated beneficiaries (primary analysis) and to HZV-unvaccinated beneficiaries who had received pneumococcal vaccination (secondary analysis). HZ outcomes in community and hospital settings were analyzed, including ophthalmic zoster (OZ) and postherpetic neuralgia (PHN). Results Among eligible beneficiaries (average age 77 years), the primary analysis found VE for community HZ of 33% (95% CI: 32%-35%) and 19% (95% CI: 17%-22%), for the first 3, and subsequent 4+ years postvaccination, respectively. In the secondary analysis, VE was, respectively, 37% (95% CI: 36%-39%) and 22% (95% CI: 20%-25%). In the primary analysis, VE for PHN was 57% (95% CI: 52%-61%) and 45% (95% CI: 36%-53%) in the first 3 and subsequent 4+ years, respectively; VE for hospitalized HZ was, respectively, 74% (95% CI: 67%-79%) and 55% (95% CI: 39%-67%). Differences in VE by age group were not significant. Conclusions In both the primary and secondary analyses, HZV provided protection against HZ across all ages, but effectiveness declined over time. VE was higher and better preserved over time for PHN and HZ-associated hospitalizations than for community HZ.

Effectiveness and Duration of Protection Provided by the Live-attenuated Herpes Zoster Vaccine in the Medicare Population Ages 65 Years and Older

Author Contributions: Dr Tamblyn and Ms Wong had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Wong, Motulsky, Tamblyn. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Wong. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Wong, Abrahamowicz. Obtained funding: Wong, Tamblyn. Administrative, technical, or material support: Tamblyn. Study supervision: Tamblyn.

Sarah Wong

Papers

Comparative Risk of Anaphylactic Reactions Associated With Intravenous Iron Products

Effectiveness and Duration of Protection Provided by the Live-attenuated Herpes Zoster Vaccine in the Medicare Population Ages 65 Years and Older

Risk of Anaphylaxis With Intravenous Iron Products.