Browsing by Subject "case report"

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    Life-Threatening Docetaxel Toxicity in a Patient With Reduced-Function CYP3A Variants: A Case Report.
    (Frontiers, 2021) Powell, Nicholas R.; Shugg, Tyler; Ly, Reynold C.; Albany, Costantine; Radovich, Milan; Schneider, Bryan P.; Skaar, Todd C.
    Docetaxel therapy occasionally causes severe and life-threatening toxicities. Some docetaxel toxicities are related to exposure, and inter-individual variability in exposure has been described based on genetic variation and drug-drug interactions that impact docetaxel clearance. Cytochrome P450 3A4 (CYP3A4) and CYP3A5 metabolize docetaxel into inactive metabolites, and this is the primary mode of docetaxel clearance. Supporting their role in these toxicities, increased docetaxel toxicities have been found in patients with reduced- or loss-of-function variants in CYP3A4 and CYP3A5. However, since these variants in CYP3A4 are rare, little is known about the safety of docetaxel in patients who are homozygous for the reduced-function CYP3A4 variants. Here we present a case of life-threatening (grade 4) pneumonitis, dyspnea, and neutropenia resulting from a single dose of docetaxel. This patient was (1) homozygous for CYP3A4*22, which causes reduced expression and is associated with increased docetaxel-related adverse events, (2) heterozygous for CYP3A4*3, a rare reduced-function missense variant, and (3) homozygous for CYP3A5*3, a common loss of function splicing defect that has been associated with increased docetaxel exposure and adverse events. The patient also carried functional variants in other genes involved in docetaxel pharmacokinetics that may have increased his risk of toxicity. We identified one additional CYP3A4*22 homozygote that received docetaxel in our research cohort, and present this case of severe hematological toxicity. Furthermore, the one other CYP3A4*22 homozygous patient we identified from the literature died from docetaxel toxicity. This case report provides further evidence for the need to better understand the impact of germline CYP3A variants in severe docetaxel toxicity and supports using caution when treating patients with docetaxel who have genetic variants resulting in CYP3A poor metabolizer phenotypes.
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    Medical decision making about long-term artificial nutrition after severe stroke: a case report
    (PubMed, 2021-07) Comer, Amber R.; Williams, Linda S.; Bartlett, Stephanie L.; D'Cruz, Lynn E.; Torke, Alexia M.; Health Sciences, School of Health and Human Sciences
    Choosing to use a percutaneous endoscopic gastrostomy (PEG tube) for long term artificial nutrition in the setting of inadequate oral intake after stroke is complex because the decision must be made in a relatively short amount of time and prognosis is often uncertain. This case study utilized interviews with attending and resident neurologists, and surrogate medical decision makers in order to examine how neurologists and surrogate medical decision makers approached the decision to either receive a PEG tube or pursue comfort measures after severe stroke in two patients. Although these two patients presented with similar clinical characteristics and faced similar medical decisions, different decisions regarding PEG tube placement were made. Major challenges included physicians who did not agree on prognosis and surrogates who did not agree on whether to place a PEG tube. These cases demonstrate the importance of the role of the surrogate medical decision maker and the necessity of physicians and surrogate medical decision makers approaching the complex decision of PEG tube placement after stroke together. Additionally, these cases highlight the differing views on what defines a good quality of life and show the vital importance of high-quality goals of care conversations about prognosis and quality of life when deciding whether to place a PEG tube after severe stroke.
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    Remarkable Response to Erdafitinib in Metastatic Lung Adenocarcinoma With FGFR Fusion
    (ASCO, 2020) Urrutia Argueta, Samuel A.; Hanna, Nasser H.; Medicine, School of Medicine