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Minimally Invasive Postmortem Intestinal Tissue Sampling In Malnourished And Acutely Ill Children Is Feasible And Informative, Erika Feutz, Wieger Voskuijl, Peter J Finch, Ta-Chiang Liu, Robert H J Bandsma, Phillip I Tarr, Christopher Alan Moxon, Kelley Vanbuskirk, Sarah Lawrence, Grace Umutesi, Kirkby D Tickell, James A Berkley, Judd L Walson, Steve Kamiza, Donna M Denno

2020-Current year OA Pubs

BACKGROUND: Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies' utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition.

METHODS: Transabdominal needle and endoscopic forceps upper and lower intestinal sampling …

Molecular Classification Of A Complex Structural Rearrangement Of The Rb1 Locus In An Infant With Sporadic, Isolated, Intracranial, Sellar Region Retinoblastoma, Kathleen M Schieffer, Margaret Shatara, Et Al.

2020-Current year OA Pubs

Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome …

Thrombotic Microangiopathy Following Onasemnogene Abeparvovec For Spinal Muscular Atrophy: A Case Series, Deepa H Chand, Craig Zaidman, Kapil Arya, Rachel Millner, Michelle A Farrar, Fiona E Mackie, Natalie L Goedeker, Vikas R Dharnidharka, Raja Dandamudi, Sandra P Reyna

2020-Current year OA Pubs

Spinal muscular atrophy is treated with onasemnogene abeparvovec, which replaces the missing survival motor neuron 1 gene via an adeno-associated virus vector. As of July 1, 2020, we had identified 3 infants who developed thrombotic microangiopathy following onasemnogene abeparvovec. Early recognition and treatment of drug-induced thrombotic microangiopathy may lessen mortality and morbidity.

Severity Of Parkinsonism Associated With Environmental Manganese Exposure, Brad A Racette, Gill Nelson, Wendy W Dlamini, Pradeep Prathibha, Jay R Turner, Mwiza Ushe, Harvey Checkoway, Lianne Sheppard, Susan Searles Nielsen

2020-Current year OA Pubs

BACKGROUND: Exposure to occupational manganese (Mn) is associated with neurotoxic brain injury, manifesting primarily as parkinsonism. The association between environmental Mn exposure and parkinsonism is unclear. To characterize the association between environmental Mn exposure and parkinsonism, we performed population-based sampling of residents older than 40 in Meyerton, South Africa (N = 621) in residential settlements adjacent to a large Mn smelter and in a comparable non-exposed settlement in Ethembalethu, South Africa (N = 95) in 2016-2020.

METHODS: A movement disorders specialist examined all participants using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3). Participants also completed an …

Hepatotoxicity Following Administration Of Onasemnogene Abeparvovec (Avxs-101) For The Treatment Of Spinal Muscular Atrophy, Deepa Chand, Franziska Mohr, Hugh Mcmillan, Francis Fonyuy Tukov, Kyle Montgomery, Aaron Kleyn, Rui Sun, Sitra Tauscher-Wisniewski, Petra Kaufmann, Gerd Kullak-Ublick

2020-Current year OA Pubs

BACKGROUND & AIMS: Spinal muscular atrophy (SMA) is an autosomal recessive, childhood-onset motor neuron disease. Onasemnogene abeparvovec (OA) is a gene therapy designed to address SMA's root cause. In pivotal mouse toxicology studies, the liver was identified as a major site of OA toxicity. Clinical data reflect elevations in serum aminotransferase concentrations, with some reports of serious acute liver injury. Prophylactic prednisolone mitigates these effects. Herein, we aim to provide pragmatic, supportive guidance for identification, management, and risk mitigation of potential drug-induced liver injury.

METHODS: Data from 325 patients with SMA who had received OA through 31 December 2019, in …