Background-This study evaluates the relationship between cytochrome P450 (CYP) 3A5 genotype and vincristine-induced peripheral neuropathy in children with precursor B cell acute lymphoblastic leukemia (preB ALL). We have shown in vitro that vincristine is metabolized significantly more efficiently by CYP3A5 than by CYP3A4. We also found that vincristine neurotoxicity is less common in African-Americans (70% express CYP3A5) than in Caucasians. We test the hypothesis that CYP3A5 expressers experience less vincristine neuropathy than do CYP3A5 non-expressers.
The data support the hypothesis pharmacogenetic polymorphisms in CYP3A5 expression contribute to variability in vincristine metabolism and neurotoxicity.
Acute gastrointestinal bleeding (GIB) can lead to significant morbidity and mortality without appropriate treatment. There are numerous causes of acute GIB including but not limited to infection, vascular anomalies, inflammatory diseases, trauma, and malignancy. The diagnostic and therapeutic approach of GIB depends on its location, severity, and etiology. The role of interventional radiology becomes vital in patients whose GIB remains resistant to medical and endoscopic treatment. Radiology offers diagnostic imaging studies and endovascular therapeutic interventions that can be performed promptly and effectively with successful outcomes. Computed tomography angiography and nuclear scintigraphy can localize the source of bleeding and provide essential information for the interventional radiologist to guide therapeutic management with endovascular angiography and transcatheter embolization. This review article provides insight into the essential role of Interventional Radiology in the management of acute GIB.
Purpose To compare the diagnostic performance of restriction spectrum imaging (RSI), with that of conventional multi-parametric (MP) magnetic resonance imaging (MRI) for prostate cancer (PCa) detection in a blinded reader-based format. Methods Three readers independently evaluated 100 patients (67 with proven PCa) who underwent MP-MRI and RSI within 6 months of systematic biopsy (N = 67; 23 with targeting performed) or prostatectomy (N = 33). Imaging was performed at 3 Tesla using a phased-array coil. Readers used a five-point scale estimating the likelihood of PCa present in each prostate sextant. Evaluation was performed in two separate sessions, first using conventional MP-MRI alone then immediately with MP-MRI and RSI in the same session. Four weeks later, another scoring session used RSI and T2-weighted imaging (T2WI) without conventional diffusion-weighted or dynamic contrast-enhanced imaging. Reader interpretations were then compared to prostatectomy data or biopsy results. Receiver operating characteristic curves were performed, with area under the curve (AUC) used to compare across groups. Results MP-MRI with RSI achieved higher AUCs compared to MP-MRI alone for identifying high-grade (Gleason score greater than or equal to 4 + 3=7) PCa (0.78 vs. 0.70 at the sextant level; P < 0.001 and 0.85 vs. 0.79 at the hemigland level; P = 0.04). RSI and T2WI alone achieved AUCs similar to MP-MRI for high-grade PCa (0.71 vs. 0.70 at the sextant level). With hemigland analysis, high-grade disease results were similar when comparing RSI + T2WI with MP-MRI, although with greater AUCs compared to the sextant analysis (0.80 vs. 0.79). Conclusion Including RSI with MP-MRI improves PCa detection compared to MP-MRI alone, and RSI with T2WI achieves similar PCa detection as MP-MRI.
IntroductionEvaluation recommendations for patients on anticoagulant and antiplatelet (ACAP) therapy that present after mild traumatic brain injury (TBI) are controversial. At our institution, an initial noncontrast head computed tomography (HCT) is performed, with a subsequent HCT performed six hours later to exclude delayed intracranial hemorrhage (ICH). This study was performed to evaluate the yield and advisability of this approach.MethodsWe performed a retrospective review of subjects undergoing evaluation for ICH after mild TBI in patients on ACAP therapy between January of 2012 and April of 2013. We assessed for the frequency of ICH on both the initial noncontrast HCT and on the routine six-hour follow-up HCT. Additionally, chart review was performed to evaluate the clinical implications of ICH, when present, and to interrogate whether pertinent clinical and laboratory data may predict the presence of ICH prior to imaging. We used multivariate generalized linear models to assess whether presenting Glasgow Coma Score (GCS), loss of consciousness (LOC), neurological or physical examination findings, international normalized ratio, prothrombin time, partial thromboplastin time, platelet count, or specific ACAP regimen predicted ICH.Results144 patients satisfied inclusion criteria. Ten patients demonstrated initial HCT positive for ICH, with only one demonstrating delayed ICH on the six-hour follow-up HCT. This patient was discharged without any intervention required or functional impairment. Presenting GCS deviation (p<0.001), LOC (p=0.04), neurological examination findings (p<0.001), clopidogrel (p=0.003), aspirin (p=0.03) or combination regimen (p=0.004) use were more commonly seen in patients with ICH.ConclusionRoutine six-hour follow-up HCT is likely not indicated in patients on ACAP therapy, as our study suggests clinically significant delayed ICH does not occur. Additionally, presenting GCS deviation, LOC, neurological examination findings, clopidogrel, aspirin or combination regimen use may predict ICH, and, in the absence of these findings, HCT may potentially be forgone altogether.
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