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Significant evidence suggests that misfolded alpha‐synuclein (aSyn), a major component of Lewy bodies, propagates in a prion‐like manner contributing to disease progression in Parkinson's disease (PD) and other synucleinopathies. In fact, timed inoculation of M83 hemizygous mice with recombinant human aSyn preformed fibrils (PFF) has shown symptomatic deficits after substantial spreading of pathogenic alpha‐synuclein, as detected by markers for the phosphorylation of S129 of aSyn. However, whether accumulated toxicity impact human‐relevant cognitive and structural neuroanatomical measures is not fully understood. Here we performed a single unilateral striatal PFF injection in M83 hemizygous mice, and using two assays with translational potential, ex vivo magnetic resonance imaging (MRI) and touchscreen testing, we examined the combined neuroanatomical and behavioral impact of aSyn propagation. In PFF‐injected mice, we observed widespread atrophy in bilateral regions that project to or receive input from the injection site using MRI. We also identified early deficits in reversal learning prior to the emergence of motor symptoms. Our findings highlight a network of regions with related cellular correlates of pathology that follow the progression of aSyn spreading, and that affect brain areas relevant for reversal learning. Our experiments suggest that M83 hemizygous mice injected with human PFF provides a model to understand how misfolded aSyn affects human‐relevant pre‐clinical measures and suggest that these pre‐clinical biomarkers could be used to detect early toxicity of aSyn and provide better translational measures between mice and human disease. [ABSTRACT FROM AUTHOR]

An editorial is presented on proper allergy documentation into an electronic health record (EHR) playing a key role in patient safety. Topics include utilizing codified allergy information within clinical decision support allowing for safety alerts notifying clinicians to the potential for harm with the administration of certain medications; and large integrated health system fortifying the EHR due to the lack of native functionality.

BACKGROUND: Asparaginase agents are vital in the treatment of acute lymphoblastic leukemia (ALL) and can be delivered via an intravenous (IV) or intramuscular (IM) injection. Hypersensitivity reaction (HSR) rates with these agents are common, multifactorial, and treatment-altering. The specific route of asparaginase administration may lead to disparate rates of HSRs and other adverse events in pediatric patients with ALL. OBJECTIVE: To analyze the role of administration route in the incidence and severity of adverse events in pediatric patients receiving asparaginase therapy. METHODS: This single-center, retrospective analysis evaluated patients receiving pegaspargase or Erwinia asparaginase from January 1, 2008, through September 30, 2015. The primary outcome measured the incidence of HSRs with IV or IM pegaspargase and IV or IM Erwinia asparaginase. Secondary outcomes included the potential role of administration route on the timing and rate of adverse drug events. RESULTS: A total of 368 patients received pegaspargase during the study period. Of this group, 199 received only IV pegaspargase, 138 received only IM pegaspargase, and 31 received both IV and IM pegaspargase. Overall, HSRs occurred in 18.6% of patients who received IV administration and 13.8% who received IM administration (P = .241). Among patients who received both routes during ALL treatment, 9.7% had an HSR. A total of 43 (76.8%) patients had an HSR during the consolidation phase of therapy. A total of 517 Erwinia asparaginase doses were administered, and only 1 patient had an HSR. We found increased antiemetic use in 28 (36.4%) of 77 IV Erwinia asparaginase doses compared with only 28 (6.4%) of 440 IM doses (P <.001). CONCLUSION: Our findings showed no significant difference in HSR rates between patients receiving IV pegaspargase and those receiving IM pegaspargase. Hypersensitivity resulting from Erwinia asparaginase were infrequent, and IV Erwinia asparaginase administration displayed more emetogenicity than the traditional IM route. [ABSTRACT FROM AUTHOR]