Search

Objectives Understanding of histiocytic disorders has been revolutionized by demonstration of mitogen-activated protein kinase (MAPK) pathway mutations, most commonly BRAF V600E. The optimal testing strategy to assess BRAF V600E is unknown. We aimed to compare performance of testing modalities, to propose a framework for evaluation of BRAF V600E mutation status in histiocytic disorders. Methods We retrospectively reviewed patients with histiocytic disorders and BRAF mutation testing on a lesional tissue specimen. Results In 120 patients, BRAF assessment included immunohistochemistry (IHC) in 97 (80.2%), polymerase chain reaction (PCR) in 35 (28.9%), and next-generation sequencing (NGS) in 62 (51.2%). Forty-five underwent both NGS and IHC. With NGS as the gold standard, the sensitivity and specificity of IHC were 82.4% and 96.4%. Three false negatives were observed in biopsy specimens with low BRAF V600E variant allele frequency or decalcified tissue. One false-positive IHC was observed in a lung biopsy specimen, likely due to antibody cross-reactivity with respiratory cilia. Among 14 with successful NGS and PCR, a single discordance was observed. Two PCR-to-IHC discrepancies were observed, including one other false-positive IHC. Conclusions Immunohistochemistry was highly specific for detection of BRAF V600E. Main caveats were false negatives and lack of detection of non- BRAF V600E mutations. We propose the use of IHC as initial screening in general practice with reflex molecular testing if negative. [ABSTRACT FROM AUTHOR]

Approximately 3-7% of adults with acute lymphoblastic leukemia (ALL) have central nervous system (CNS) involvement at diagnosis. Commonly used IT therapies include methotrexate (MTX), cytarabine (ARAC), and hydrocortisone, or a combination of all three called IT triple therapy (ITT). This has been observed in patients receiving two or more doses of MTX per week and is related to a continuously elevated concentration of MTX in CSF, which correlates with our patient's case [[5], [9]]. [Extracted from the article]

The United States Congress has become increasingly concerned that the agricultural crops of economic importance in the United States could be signifIcantly stressed by global environmental changes, and has recognized that USDA data bases can provide significant information for policy makers and resource managers to use in addressing this problem. This paper describes three years of progress in a project designed to identify USDA global environmental change information, (including datasets, models, and Geographic Information System (GIs) applications), assess the quantity and quality of this information, and make metadata concerning this information widely available electronically. The project also addresses the preservation of data at risk of being lost, and ways to integrate information for the assessment of specific issues. [ABSTRACT FROM PUBLISHER]