Citations

Background and Purpose— Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods— STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0–2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results— Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P =0.001) and distal access catheter (83/235 [35%]; P =0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P <0.001) and distal access catheter (129/234 [55%]; P =0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P =0.007) and distal access catheter (113/218 [52%]; P =0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions— BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

AbstractPrimary aneurysmal bone cyst (ABC) is a benign multiloculated cystic lesion of bone that is defined cytogenetically by USP6 gene rearrangements. Rearrangements involving USP6 are promoter swaps, usually generated by fusion of the noncoding upstream exons of different partner genes with exon 1 or 2 of USP6, thus leading to transcriptional upregulation of full‐length USP6 coding sequence. Testing for USP6 rearrangements is used diagnostically to distinguish it from secondary ABC and other giant cell‐rich primary bone tumors. In this report, we present a case of a 16‐year‐old male with a primary ABC of the left distal femur. USP6 break apart fluorescence in situ hybridization was positive for a rearrangement and conventional chromosome analysis identified a reciprocal X;17 translocation. In order to identify the putative USP6 fusion partner, we performed RNA sequencing and uncovered a novel USP9X‐USP6 promoter swap fusion. This result was confirmed by reverse transcription‐polymerase chain reaction (RT‐PCR) and by mate pair sequencing thus showing the utility of these alternative methodologies in identifying novel fusion candidates. Ubiquitin‐specific protease 9X (USP9X), like USP6, encodes a highly conserved substrate‐specific deubiquitylating enzyme. USP9X is highly expressed in a number of tissue types and acts as both an oncogene and tumor suppressor in several human cancers. We conclude that oncogenic activation of USP6 via USP9X promoter exchange represents a novel driver of primary ABC formation.

Level of Evidence : 5 Technical Efficacy : Stage 5 J. Magn. Reson. Imaging 2019.

Male and female glioblastomas are biologically distinct, and improving outcomes may require sex-specific approaches to treatment.

Mechanical thrombectomy (MT) is the standard of care for patients who present with an acute ischemic stroke within 6 hours of symptom onset, and up to 24 hours in appropriately selected patients. However, optimal postoperative management of these patients remains uncertain, especially with regard to blood pressure control. To review the existing literature to define potential blood pressure goals in the immediate postoperative period in patients who undergo MT for acute ischemic stroke. The topic was defined through a clinical scenario and the subsequent development of a targeted clinical question. A literature search was performed, with relevant articles selected, one of which, a prospective observational study, was critically appraised. Participants included neurology residents and consultants, a medical librarian, clinical epidemiologists, as well as content experts from vascular neurology and interventional neuroradiology. Permissive hypertension (defined as <220/120 or <180/105 mm Hg as per the American Heart Association/American Stroke Association guidelines) may be harmful in the postoperative period following MT, especially in patients who were successfully recanalized. Moderate blood pressure control (<160/90) was found to be a predictor of improved 3-month mortality on multivariable logistic regression analysis in patients who sustained successful reperfusion [odds ratio (OR), 0.08; 95% confidence interval (CI), 0.01-0.054; P=0.01]. A 10 mm Hg increase in systolic blood pressure was found to result in a lower OR of having a favorable 3-month functional independence (OR, 0.70; 95% CI, 0.56-0.85; P=0.001) as well as higher rates of 3-month mortality (OR, 1.49; 95% CI, 1.18-1.88; P=0.001). Blood pressure goals in the immediate postoperative period in patients who undergo MT should differ than those who do not undergo MT, with data suggesting that lower blood pressure than permissive hypertension may be related to improved outcomes, especially in cases of successful reperfusion. However, current data are derived from observational studies; further studies, preferably in the form of randomized-controlled trials, are needed to further clarify the relationship between postoperative blood pressures and outcomes in this patient population.

Abstract The CHEK2 gene and its encoded protein Chk2 have a well-known role in cancers, especially those related to breast cancer mediated through the BRCA1 gene. Additionally Chk2 has a crucial role in DNA repair, apoptosis and the cell cycle, which is why classification of variants of uncertain significance (VUS) is an area highly sought for a better elucidation of the “genomic effect” that results. Because it can often take years before enough clinical data is accumulated, and the costly and expensive functional analysis for individual variants presents a significant hurdle, it is important to identify other tools to help aid in clarifying the impact of specific variants on a protein's function and eventually the patient's health outcome. Here we describe a newly identified CHEK2 variant and analyze with an integrated approach combining genomics (whole exome analysis), clinical study, radiographic imaging, and protein informatics to identify and predict the functional impact of the VUS on the protein's behavior and predicted impact on the related pathways. The observed and analyzed defects in the protein were consistent with the expected clinical effect. Here, we support the use of personalized protein modeling and informatics and further our goal of developing a large-scale protein deposition archive for all protein-level VUS.