Multicenter evaluation of a new rapid automated human immunodeficiency virus antigen detection assay

Although human immunodeficiency virus (HIV) antigen assays are of limited value for monitoring antiretroviral therapy, they play an important role for confirmatory testing of fourth generation HIV screening enzyme immunoassay (EIA) reactive samples. In a multicenter study, a new automated rapid p24 antigen assay, Elecsys HIV Ag (Roche Diagnostics Boehringer Mannheim GmbH, Penzberg, Germany), was compared to FDA licensed tests (Abbott HIV-1 Ag monoclonal and Coulter HIV-1 p24 antigen assay). In the evaluation 27 seroconversion panels were included, sera from the acute phase of infection, single and follow-up samples from HIV antibody positive patients, dilution series of HIV antigen positive standards, sera and cell culture supernatants infected with different HIV-1 subtypes (A-H, and O) HIV-2 and recombinant HIV-1 (gag/env) isolates. To challenge the specificity of the new assay, 2565 unselected blood donors, sera from pregnant women, dialysis and hospitalized patients and 407 potentially cross-reactive samples were investigated. Acute HIV infection was detected in three to eight seroconversion panels earlier with Elecsys HIV Ag than with the alternative assays. Higher numbers of serum samples from HIV infected patients tested positive by Elecsys HIV Ag than with the comparative assays. All HIV-1 subtypes and HIV-2 isolates were recognized with Elecsys HIV Ag. Abbott HIV-1 Ag monoclonal and Coulter HIV-1 p24 antigen assay showed a variable sensitivity for the different HIV-1 subtypes. The specificity of Elecsys HIV Ag and Coulter HIV-1 p24 antigen assay were 99.8 and 99.93%, respectively. All the eight sera that were false reactive by Elecsys HIV Ag were tested negative with the Elecsys HIV Ag Neutralization Test. In conclusion, Elecsys HIV Ag was more sensitive than the alternative assays and showed a high specificity in combination with the neutralization assay. The very short incubation time of 18 min and the fully automated procedure of Elecsys HIV Ag which permits direct testing from the primary patient blood collection tube, represent a major improvement for routine laboratory diagnosis in comparison to the alternative assays.     

Impaired calcification around matrix vesicles of growth plate and bone in alkaline phosphatase-deficient mice

The presence of skeletal hypomineralization was confirmed in mice lacking the gene for bone alkaline phosphatase, ie, the tissue-non-specific isozyme of alkaline phosphatase (TNAP). In this study, a detailed characterization of the ultrastructural localization, the relative amount and ultrastructural morphology of bone mineral was carried out in tibial growth plates and in subjacent metaphyseal bone of 10-day-old TNAP knockout mice. Alizarin red staining, microcomputerized tomography (micro CT), and FTIR imaging spectroscopy (FT-IRIS) confirmed a significant overall decrease of mineral density in the cartilage and bone matrix of TNAP-deficient mice. Transmission electron microscopy (TEM) showed diminished mineral in growth plate cartilage and in newly formed bone matrix. High resolution TEM indicated that mineral crystals were initiated, as is normal, within matrix vesicles (MVs) of the growth plate and bone of TNAP-deficient mice. However, mineral crystal proliferation and growth was inhibited in the matrix surrounding MVs, as is the case in the hereditary human disease hypophosphatasia. These data suggest that hypomineralization in TNAP-deficient mice results primarily from an inability of initial mineral crystals within MVs to self-nucleate and to proliferate beyond the protective confines of the MV membrane. This failure of the second stage of mineral formation may be caused by an excess of the mineral inhibitor pyrophosphate (PPi) in the extracellular fluid around MVs. In normal circumstances, PPi is hydrolyzed by the TNAP of MVs' outer membrane yielding monophosphate ions (Pi) for incorporation into bone mineral. Thus, with TNAP deficiency a buildup of mineral-inhibiting PPi would be expected at the perimeter of MVs.     

Real-World Treatment Patterns,Overall Survival,and Occurrence and Costs of Adverse Events Associated With First-line Therapies for Medicare Patients 65 Years and Older With Advanced Non–small-cell Lung Cancer: A Retrospective Study

Purpose

This study sought to better understand real-world treatment patterns, overall and non–small-cell lung cancer (NSCLC)-specific survival, adverse event (AE) occurrence, and economic impact of first-line cancer therapies in Medicare patients.

Dynamics of EGFR Mutation Load in Plasma for Prediction of Treatment Response and Disease Progression in Patients With EGFR-Mutant Lung Adenocarcinoma

Background

The assessment of epidermal growth factor receptor (EGFR) mutations is crucial for the management of patients with lung adenocarcinoma. Circulating tumor DNA (ctDNA)-based assessment offers advantages over tumor as a minimally invasive method able to capture tumor heterogeneity.

Recreational physical activity and survival in African-American women with ovarian cancer

Purpose

While recreational physical activity (RPA) has been associated with reduced mortality in breast, colorectal, and prostate cancers, evidence for epithelial ovarian cancer (EOC) is limited. Most EOC studies have been in predominantly white populations, although inactivity is more prevalent and survival is poorer among African-American (AA) women. We examined RPA before and after EOC diagnosis and associations with survival among AA women.

Methods

We analyzed data from 264 EOC survivors enrolled in a population-based, case–control study who completed surveys that included questions about pre- and post-diagnosis RPA. Data were collected on RPA frequency, intensity, and duration before diagnosis and approximately 1 year after the baseline interview. We calculated metabolic equivalent of task (MET)-hours/week for pre- and post-diagnosis RPA, and evaluated associations with risk of mortality using Cox proportional hazards models.

Results

RPA before diagnosis was not associated with mortality. Hazard ratios (HRs) for post-diagnosis RPA were <?1.0 but not statistically significant after adjustment for covariates; HRs were 0.94 (95% CI 0.58, 1.54) for >?0–9 MET-hours/week and 0.53 (95% CI 0.21, 1.35) for >?9 MET-hours/week.

Conclusions

Our results suggest that RPA may be inversely associated with mortality among AA women with ovarian cancer, although it is possible that the present study was underpowered to detect an association. There is a clear need for more studies of RPA after diagnosis in EOC survivors with attention to potential differences by race.