Accelerated diagnostic algorithms with hs-cTn have ≥ 92% sensitivity but lower specificity for diagnosing AMI.

SOURCE CITATION: Lee CC, Huang SS, Yeo YH, et al. High-sensitivity-cardiac troponin for accelerated diagnosis of acute myocardial infarction: a systematic review and meta-analysis. Am J Emerg Med. 2019. [Epub ahead of print]. 31932131.

Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas.

Astrocytomas are the most common type of brain tumors in children. Activated BRAF protein kinase mutations are characteristic of pediatric astrocytomas with KIAA1549-BRAF fusion genes typifying low-grade astrocytomas and (V600E)BRAF alterations characterizing distinct or higher-grade tumors. Recently, BRAF-targeted therapies, such as vemurafenib, have shown great promise in treating V600E-dependent melanomas. Like (V600E)BRAF, BRAF fusion kinases activate MAPK signaling and are sufficient for malignant transformation; however, here we characterized the distinct mechanisms of action of KIAA1549-BRAF and its differential responsiveness to PLX4720, a first-generation BRAF inhibitor and research analog of vemurafenib. We found that in cells expressing KIAA1549-BRAF, the fusion kinase functions as a homodimer that is resistant to PLX4720 and accordingly is associated with CRAF-independent paradoxical activation of MAPK signaling. Mutagenesis studies demonstrated that KIAA1549-BRAF fusion-mediated signaling is diminished with disruption of the BRAF kinase dimer interface. In addition, the KIAA1549-BRAF fusion displays increased binding affinity to kinase suppressor of RAS (KSR), an RAF relative recently demonstrated to facilitate MEK phosphorylation by BRAF. Despite its resistance to PLX4720, the KIAA1549-BRAF fusion is responsive to a second-generation selective BRAF inhibitor that, unlike vemurafenib, does not induce activation of wild-type BRAF. Our data support the development of targeted treatment paradigms for BRAF-altered pediatric astrocytomas and also demonstrate that therapies must be tailored to the specific mutational context and distinct mechanisms of action of the mutant kinase.

Indications for hip arthroscopy in pediatric patients a systematic review.

The purpose of this study was to evaluate the current available literature on hip arthroscopy and determine the clinical indications in the pediatric patient population (age ≤ 18). In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), a comprehensive literature search was performed on the 23 October 2018 using PubMed, Cochrane Library, Embase and e-books to identify research surrounding the use of hip arthroscopy in the pediatrics. Exclusion criteria were studies that described joints other than the hip, animal studies, systematic reviews, open procedures and those that reported solely on patients aged 19-year-old and older. From 232 studies, 57 were reviewed in detail; 17 articles were removed as their indication fell into a category of 'diagnostic hip arthroscopy for pain' or no clear separation between the data on the adult and pediatric population could be made in a full text review of the paper. Eleven categories were identified as indications for hip arthroscopy in the pediatric population. At best a Grade C recommendation can be made to support the use of hip arthroscopy in the pediatric population. Our results support our hypothesis. Despite the exponential increase in hip arthroscopy over the last decade, limited evidence exists in support of its use in the pediatric (≤18) population. Our findings support the need for further research in delineating the indications for its use, as clearly arthroscopy may be advantageous in many situations, particularly in light of the alternatives.