Early Real-World Experience with CoreValve Evolut PRO and R Systems for Transcatheter Aortic Valve Replacement.

OBJECTIVES: The purpose of this study was to compare the efficacy and safety of the Evolut PRO to the Evolut R valve in a real-world setting. BACKGROUND: The next-generation self-expanding transcatheter aortic valve replacement (TAVR) system, the CoreValve Evolut PRO was designed with an outer pericardial skirt to improve valve-sealing performance. Safety and efficacy of this valve have not previously been compared to its predecessor, the Evolut R valve. METHODS: We retrospectively studied 134 patients who underwent TAVR with the Evolut PRO or Evolut R valve over one year at a tertiary center. Endpoints, defined by the Valve Academic Research Consortium-2 criteria, included device success, paravalvular leak (PVL), and a composite safety endpoint including mortality, stroke, major vascular complications, life-threatening bleeding, acute kidney injury, coronary artery obstruction, and repeat procedure for valve-related dysfunction. RESULTS: 60 Evolut PRO and 56 Evolut R patients met the study criteria. Both groups had similar device success rates (90 vs. 89%, p=0.44). Incidence of moderate PVL was similar on discharge (5 vs. 11%, p=0.68) and at 30 days (11 vs. 13%, p=0.79), with nil incidence of severe PVL. There were no mortalities, and the VARC-2 safety endpoint at 30 days was comparable. CONCLUSION: Despite the additional pericardial skirt and larger sheath size of Evolut PRO, outcomes were comparable between the two Evolut systems, supporting adoption of the newest generation valve in the management of severe aortic stenosis as well as continued use of the Evolut R in patients with smaller vasculature warranting a lower profile device.

Proteogenomic Network Analysis of Context-Specific KRAS Signaling in Mouse-to-Human Cross-Species Translation.

The highest frequencies of KRAS mutations occur in colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDAC). The ability to target downstream pathways mediating KRAS oncogenicity is limited by an incomplete understanding of the contextual cues modulating the signaling output of activated K-RAS. We performed mass spectrometry on mouse tissues expressing wild-type or mutant Kras to determine how tissue context and genetic background modulate oncogenic signaling. Mutant Kras dramatically altered the proteomes and phosphoproteomes of preneoplastic and neoplastic colons and pancreases in a context-specific manner. We developed an approach to statistically humanize the mouse networks with data from human cancer and identified genes within the humanized CRC and PDAC networks synthetically lethal with mutant KRAS. Our studies demonstrate the context-dependent plasticity of oncogenic signaling, identify non-canonical mediators of KRAS oncogenicity within the KRAS-regulated signaling network, and demonstrate how statistical integration of mouse and human datasets can reveal cross-species therapeutic insights.

Percutaneous coronary intervention: 2017 in review.

In an effort to keep the interventional community up-to-date with the abundant amount of new data, we have selected what we believe to be the most important publications in percutaneous coronary intervention from January 1, 2017 to December 2017.

Mechanically stimulated biomarkers signal cartilage changes over 5 years consistent with disease progression in medial knee osteoarthritis patients.

Using serum biomarkers to assess osteoarthritis (OA) disease state and risks of progression remain challenging. This study tested the hypothesis that changes to serum biomarkers in response to a mechanical stimulus in patients with medial knee OA signal cartilage thickness changes 5 years later. Specifically, serum concentrations of a collagen degradation marker (C1,2C) and a chondroitin sulfate synthesis marker (CS846) were measured 0.5 and 5.5 hours after a 30-min walk in 16 patients. Regional cartilage thickness changes measured from magnetic resonance images obtained at study entry and at 5-year follow-up were tested for correlations with baseline biomarker changes after mechanical stimulus, and for differences between groups stratified based on whether biomarker levels increased or decreased. Results showed that an increase in the degradation biomarker C1,2C correlated with cartilage thinning of the lateral tibia (R = -0.63, p = 0.009), whereas an increase in the synthesis marker CS846 correlated with cartilage thickening of the lateral femur (R = 0.76, p = 0.001). Changes in C1,2C and CS846 were correlated (R2 = 0.28, p = 0.037). Subjects with increased C1,2C had greater (p = 0.05) medial tibial cartilage thinning than those with decreased C1,2C. In conclusion, the mechanical stimulus appeared to metabolically link the biomarker responses where biomarker increases signaled more active OA disease states. The findings of medial cartilage thinning for patients with increases in the degradation marker and correlation of cartilage thickening in the less involved lateral femur with increases in the synthetic marker were consistent with progression of medial compartment OA. Thus, the mechanical stimulus facilitated assessing OA disease states using serum biomarkers. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:891-897, 2018.