The successful treatment of 5-fluorouracil (5-FU) overdose in a patient with malignancy and HIV/AIDS with uridine triacetate

According to the NIH, about 275 000 patients receive treatment with 5-Fluorouracil (5-FU) and more than 1300 die from 5-FU toxicity every year from life-threatening myelosuppression, gastrointestinal complications, and neurotoxicity. Immunocompromised persons are at higher risk of developing toxicity. Recently uridine triacetate (Vistagard®) has been approved by the Food and Drug Administration (FDA) as the only specific antidote available for 5-FU poisoning. In a clinical trial (n = 135), 96% of patients with 5-FU toxicity recovered after treatment, where as in a historical control group only 10% survived. This is the first published case report of survival after 5-FU overdose who also was immunocompromised from HIV/AIDs. A 52 year old male with history of HIV/AIDS (CD4 70), CNS toxoplasmosis and anal cancer presented to the emergency department after realizing he had received an entire course of 5-FU in 24 instead of 96 h. Treatment with uridine triacetate was arranged in the emergency department. After receiving treatment the patient was asymptomatic and had an uncomplicated hospital course. 5-FU poisoning must be recognized early as uridine triacetate is approved by the FDA for use within 96 h following the end of 5-FU administration. Emergency medicine physicians should promptly recognize and treat 5-FU poisoning. However, this may be challenging as patients may not seek medical attention until many hours or several days after last administration since symptoms are often delayed with 5-FU poisoning.     

Prognostic capabilities and clinical utility of cell cycle progression testing,prostate imaging reporting and data system,version 2, and clinicopathologic data in management of localized prostate cancer

ObjectivesTo compare the prognostic capabilities and clinical utility of the cell cycle progression (CCP) gene expression classifier test, multiparametric magnetic resonance imaging (mpMRI) with Prostate Imaging Reporting and Data System (PI-RADS) scoring, and clinicopathologic data in select prostate cancer (PCa) medical management scenarios.Patients and methodsRetrospective, observational analysis of patients (N = 222) ascertained sequentially from a single urology practice from January 2015 to June 2018. Men were included if they had localized PCa, a CCP score, and an mpMRI PI-RADS v2 score. Cohort 1 (n = 156): men with newly diagnosed PCa, with or without a previous negative biopsy. Cohort 2 (n = 66): men who initiated active surveillance (AS) without CCP testing, but who received the test during AS. CCP was combined with the UCSF Cancer of the Prostate Risk Assessment (CAPRA) score to produce a clinical cell-cycle risk (CCR) score, which was reported in the context of a validated AS threshold. Spearman's rank correlation test was used to evaluate correlations between variables. Generalized linear models were used to predict binary Gleason score category and medical management selection (AS or curative therapy). Likelihood-ratio tests were used to determine predictor significance in both univariable and multivariable models.ResultsIn the combined cohorts, modest but significant correlations were observed between PI-RADS score and CCP (r_s = 0.22, P = 8.1 × 10^?4), CAPRA (r_s= 0.36, P = 4.8 × 10^?8), or CCR (r_s = 0.37, P = 2.0 × 10^?8), suggesting that much of the prognostic information captured by these measures is independent. When accounting for CAPRA and PI-RADS score, CCP was a significant predictor of higher-grade tumor after radical prostatectomy, with the resected tumor approximately 4 times more likely to harbor Gleason ≥4+3 per 1-unit increase in CCP in Cohort 1 (Odds Ratio [OR], 4.10 [95% confidence interval [CI], 1.46, 14.12], P = 0.006) and in the combined cohorts (OR, 3.72 [95% CI, 1.39, 11.88], P = 0.008). On multivariable analysis, PI-RADS score was not a significant predictor of post-radical prostatectomy Gleason score. Both CCP and CCR were significant and independent predictors of AS versus curative therapy in Cohort 1 on multivariable analysis, with each 1-unit increase in score corresponding to an approximately 2-fold greater likelihood of selecting curative therapy (CCP OR, 2.08 [95% CI, 1.16, 3.94], P = 0.014) (CCR OR, 2.33 [95% CI, 1.48, 3.87], P = 1.5 × 10^?4). CCR at or below the AS threshold significantly reduced the probability of selecting curative therapy over AS (OR, 0.28 [95% CI, 0.13, 0.57], P = 4.4 × 10^?4), further validating the clinical utility of the AS threshold.ConclusionCCP was a better predictor of both tumor grade and subsequent patient management than was PI-RADS. Even in the context of targeted biopsy, molecular information remains essential to ensure precise risk assessment for men with newly diagnosed PCa.     

Perceptions of Home Dialysis Training and Experience Among US Nephrology Fellows

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Etiology and Therapeutic Management of Erythema Nodosum During Pregnancy: An Update

Erythema nodosum (EN) is the most common form of panniculitis. It is characterized by erythematous, raised, tender nodules that usually occur bilaterally on the extensor surfaces of the lower extremities. EN is associated with many underlying conditions including infection, sarcoidosis, malignancy, and pregnancy. Its underlying etiology, however, is unknown in up to half of cases. Pregnancy is thought to create an optimal background for EN to develop, although the exact mechanisms are unclear. Immune complexes may play a role in the pathogenesis of EN during pregnancy, or EN may be a hypersensitivity reaction to either estrogens or progesterone. EN is a self-limiting process, and non-pharmacologic means such as bed rest and elastic web bandages may be sufficient to control the symptoms. Potassium iodide, systemic and intralesional corticosteroids, non-steroidal anti-inflammatory drugs, salicylates, tumor necrosis factor-α inhibitors, hydroxychloroquine, colchicine, and dapsone are other treatment options available, but some of these drugs are contraindicated in pregnancy while others are considered safe. Before prescribing one of these treatments to a pregnant patient, the patient’s obstetrician should be consulted, and a careful risk-benefit analysis should be performed.     

Nanoscale mapping of refractive index by using scattering-type scanning near-field optical microscopy

We present a novel method for nanoscale reconstruction of complex refractive index by using scattering-type Scanning Near-field Optical Microscopy (s-SNOM). Our method relies on correlating s-SNOM experimental image data with computational data obtained through simulation of the classical oscillating point-dipole model. This results in assigning a certain dielectric function for every pixel of the s-SNOM images, which further results in nanoscale mapping of the refractive index. This method is employed on human erythrocytes to demonstrate the approach in a biologically relevant manner. The presented results advance the current knowledge on the capabilities of s-SNOM to extract quantitative information with nanoscale resolution from optical data sets with biological application.