Clinical use of [TIMP-2]•[IGFBP7] biomarker testing to assess risk of acute kidney injury in critical care: guidance from an expert panel.

BACKGROUND: The first FDA-approved test to assess risk for acute kidney injury (AKI), [TIMP-2]•[IGFBP7], is clinically available in many parts of the world, including the USA and Europe. We sought to understand how the test is currently being used clinically. METHODS: We invited a group of experts knowledgeable on the utility of this test for kidney injury to a panel discussion regarding the appropriate use of the test. Specifically, we wanted to identify which patients would be appropriate for testing, how the results are interpreted, and what actions would be taken based on the results of the test. We used a modified Delphi method to prioritize specific populations for testing and actions based on biomarker test results. No attempt was made to evaluate the evidence in support of various actions however. RESULTS: Our results indicate that clinical experts have developed similar practice patterns for use of the [TIMP-2]•[IGFBP7] test in Europe and North America. Patients undergoing major surgery (both cardiac and non-cardiac), those who were hemodynamically unstable, or those with sepsis appear to be priority patient populations for testing kidney stress. It was agreed that, in patients who tested positive, management of potentially nephrotoxic drugs and fluids would be a priority. Patients who tested negative may be candidates for "fast-track" protocols. CONCLUSION: In the experience of our expert panel, biomarker testing has been a priority after major surgery, hemodynamic instability, or sepsis. Our panel members reported that a positive test prompts management of nephrotoxic drugs as well as fluids, while patients with negative results are considered to be excellent candidates for "fast-track" protocols.

Adjusting the neochords height for better leaflets coaptation following mitral valve repair.

Often times, in mitral valve repair techniques, the height of the newly placed Gore-Tex sutures needs correction to achieve better mitral valve leaflet coaptation or to correct systolic anterior motion (SAM). Herein, a less challenging "Hornet" technique to accurately adjust artificial chordal length is described. This technique describes a way to adjust/shorten the Gore-Tex chords, should they need revision. Ideally, this should not be needed, however due to the circumstances for mitral valve repair, this is sometimes necessary. With the annuloplasty band already in place, it is somewhat harder to reinsert new chords and hence, this technique may be beneficial.

Aortic Valve Replacement in 8 Adults with Anomalous Aortic Origin of Coronary Artery.

Patients with anomalous origin of a coronary artery during aortic valve replacement (AVR) are at risk of coronary compromise. Large case series are lacking. In this retrospective study, we review our experience with this condition. From August 2014 through June 2016, 8 adult patients (mean age, 74 ± 17.5 yr; age range, 33-86 yr; 5 men) with anomalous aortic origin of a coronary artery underwent surgical or transcatheter AVR at our institution. Six patients had aortic stenosis; 2 had aortic insufficiency, one of whom had an associated aortic root aneurysm. In 7 patients, the left anomalous coronary artery originated from the right aortic sinus, and in one, the right coronary artery arose from the left cusp. The anatomic course was revealed by means of 3-dimensional computed tomographic angiography. No patient underwent primary aortic reimplantation of the anomalous artery. Two had the artery mobilized from encircling the annulus too closely and then underwent coronary artery bypass grafting. Two high-risk patients underwent transcatheter AVR. After surgical AVR, 2 patients had perioperative myocardial infarction caused by coronary compression, so percutaneous coronary intervention was performed. One patient died of sepsis 3 months after discharge from the hospital. In our patients, AVR sometimes led to severe perioperative complications. Successful AVR depended on 3-dimensional computed tomographic angiographic findings, individual anatomic variations, and appropriate treatment choices.

An Introduction to the Mathematical Modeling in the Study of Cancer Systems Biology.

BACKGROUND: Frequently occurring in cancer are the aberrant alterations of regulatory onco-metabolites, various oncogenes/epigenetic stochasticity, and suppressor genes, as well as the deficient mismatch repair mechanism, chronic inflammation, or those deviations belonging to the other cancer characteristics. How these aberrations that evolve overtime determine the global phenotype of malignant tumors remains to be completely understood. Dynamic analysis may have potential to reveal the mechanism of carcinogenesis and can offer new therapeutic intervention. AIMS: We introduce simplified mathematical tools to model serial quantitative data of cancer biomarkers. We also highlight an introductory overview of mathematical tools and models as they apply from the viewpoint of known cancer features. METHODS: Mathematical modeling of potentially actionable genomic products and how they proceed overtime during tumorigenesis are explored. This report is intended to be instinctive without being overly technical. RESULTS: To date, many mathematical models of the common features of cancer have been developed. However, the dynamic of integrated heterogeneous processes and their cross talks related to carcinogenesis remains to be resolved. CONCLUSIONS: In cancer research, outlining mathematical modeling of experimentally obtained data snapshots of molecular species may provide insights into a better understanding of the multiple biochemical circuits. Recent discoveries have provided support for the existence of complex cancer progression in dynamics that span from a simple 1-dimensional deterministic system to a stochastic (ie, probabilistic) or to an oscillatory and multistable networks. Further research in mathematical modeling of cancer progression, based on the evolving molecular kinetics (time series), could inform a specific and a predictive behavior about the global systems biology of vulnerable tumor cells in their earlier stages of oncogenesis. On this footing, new preventive measures and anticancer therapy could then be constructed.

How to Control Subannular Hemorrhage during Aortic Root Enlarging Procedures.

We describe an effective suture technique to control the persistent subannular bleeding at the aortoventricular curtain in four patients with aortic stenosis and small annulus who underwent aortic root enlargement and patch reconstruction. This technique approximates the left atrial roof to the aortic root without the need for re-replacement of the aortic prosthesis or revision of the patch. Reintervention for aortic root, valve, or the residual aorta was not required.

How do cancer cells replenish their fuel supply?

BACKGROUND: Multiple genetic changes, availability of cellular nutrients and metabolic alterations play a pivotal role in oncogenesis AIMS: We focus on cancer cell's metabolic properties, and we outline the cross talks between cellular oncogenic growth pathways in cancer metabolism. The review also provides a synopsis of the relevant cancer drugs targeting metabolic activities that are at various stages of clinical development. METHODS: We review literature published within the last decade to include select articles that have highlighted energy metabolism crucial to the development of cancer phenotypes. RESULTS: Cancer cells maintain their potent metabolism and keep a balanced redox status by enhancing glycolysis and autophagy and rerouting Krebs cycle intermediates and products of ß-oxydation. CONCLUSIONS: The processes underlying cancer pathogenesis are extremely complex and remain elusive. The new field of systems biology provides a mathematical framework in which these homeostatic dysregulation principles may be examined for better understanding of cancer phenotypes. Knowledge of key players in cancer-related metabolic reprograming may pave the way for new therapeutic metabolism-targeted drugs and ultimately improve patient care.