Risk Factors for Major Early Adverse Events Related to Cardiac Catheterization in Children and Young Adults With Pulmonary Hypertension: An Analysis of Data From the IMPACT (Improving Adult and Congenital Treatment) Registry.

BACKGROUND: Cardiac catheterization is the gold standard for assessment and follow-up of patients with pulmonary hypertension (PH). To date, there are limited data about the factors that influence the risk of catastrophic adverse events after catheterization in this population. METHODS AND RESULTS: A retrospective multicenter cohort study was performed to measure risk of catastrophic adverse outcomes after catheterization in children and young adults with PH and identify risk factors for these outcomes. All catheterizations in children and young adults, aged 0 to 21 years, with PH at hospitals submitting data to the IMPACT (Improving Adult and Congenital Treatment) registry between January 1, 2011, and December 31, 2015, were studied. Using mixed-effects multivariable regression, we assessed the association between prespecified subject-, procedure-, and center-level covariates and the risk of death, cardiac arrest, or mechanical circulatory support during or after cardiac catheterization. A total of 8111 procedures performed in 7729 subjects at 77 centers were studied. The observed risk of the composite outcome was 1.4%, and the risk of death before discharge was 5.2%. Catheterization in prematurely born neonates and nonpremature infants was associated with increased risk of catastrophic adverse event, as was precatheterization treatment with inotropes and lower systemic arterial saturation. Secondary analyses demonstrated the following: (1) increasing volumes of catheterization in patients with PH were associated with reduced risk of composite outcome (odds ratio, 0.8 per 10 procedures; CONCLUSIONS: Young patients with PH are a high-risk population for diagnostic and interventional cardiac catheterization. Hospital experience with PH is associated with reduced risk, independent of total catheterization case volume

Percutaneous Transvenous Melody Valve-in-Ring Procedure for Mitral Valve Replacement

ObjectivesThe purpose of this study was to demonstrate the feasibility of percutaneous transvenous mitral valve-in-ring (VIR) implantation using the Melody valve in an ovine model.BackgroundThe recurrence of mitral regurgitation following surgical mitral valve (MV) repair in both adult and pediatric patients remains a significant clinical problem. Mitral annuloplasty rings are commonly used in MV repair procedures and may serve as secure landing zones for percutaneous valves.MethodsFive sheep underwent surgical MV annuloplasty (24 mm, n = 2; 26 mm, n = 2; 28 mm, n = 1). Animals underwent cardiac catheterization with VIR implantation via a transfemoral venous, transatrial septal approach 1 week following surgery. Hemodynamic, angiographic, and echocardiographic data were recorded before and after VIR.ResultsVIR was technically successful and required <1 h of procedure time in all animals. Fluoroscopy demonstrated securely positioned Melody valves within the annuloplasty ring in all animals. Angiography revealed no significant MV regurgitation in 4 and moderate central MV regurgitation in the animal with the 28-mm annuloplasty. All animals demonstrated vigorous left ventricular function, no outflow tract obstruction, and no aortic valve insufficiency.ConclusionsThis study demonstrated the feasibility of a purely percutaneous approach to MV replacement in patients with preexisting annuloplasty rings. This novel approach may be of particular benefit to patients with failed repair of ischemic mitral regurgitation and in pediatric patients with complex structural heart disease

Comprehensive comparative outcomes in children with congenital heart disease: The rationale for the Congenital Catheterization Research Collaborative

Clinical research in the treatment of patients with congenital heart disease (CHD) is limited by the wide variety of CHD manifestations and therapeutic options as well as the generally low incidence of CHD. The availability of comprehensive, contemporary outcomes studies is therefore limited. This inadequacy may result in a lack of data‐driven medical decision making. In 2013, clinician scientists at two centers began a research collaboration, the Congenital Catheterization Research Collaborative (CCRC). Over time, the CCRC has grown to include nine cardiac centers from across the United States, with a common data coordinating center. The CCRC seeks to generate high‐quality, contemporary, statistically robust, and generalizable outcomes research which can help address important clinical questions in the treatment of CHD. To date, the CCRC has reported on multicenter outcomes in: neonates with congenital aortic stenosis, infants undergoing right ventricular decompression for pulmonary atresia and intact ventricular septum, and infants with ductal‐dependent pulmonary blood flow. The CCRC has been successful at leveraging large multicenter cohorts of patients in a contemporary period to perform comparative studies. In the future, the CCRC plans to continue to perform hypothesis‐driven retrospective and prospective observational studies of CHD populations where controversy exists or where novel interventions or therapies have emerged. Quality improvement efforts including lesion‐specific registry development may be an additional potential future target.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149494/1/chd12737.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149494/2/chd12737_am.pd

Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma

BACKGROUND: We previously identified brain type fatty acid-binding protein (FABP7) as a prognostic marker for patients with glioblastoma (GBM). Increased expression of FABP7 is associated with reduced survival. To investigate possible molecular mechanisms underlying this association, we compared the expression and subcellular localization of FABP7 in non-tumor brain tissues with different types of glioma, and examined the expression of FABP7 and epidermal growth factor receptor (EGFR) in GBM tumors. METHODS: Expression of FABP7 in non-tumor brain and glioma specimens was examined using immunohistochemistry, and its correlation to the clinical behavior of the tumors was analyzed. We also analyzed the association between FABP7 and EGFR expression in different sets of GBM specimens using published DNA microarray datasets and semi-quantitative immunohistochemistry. In vitro migration was examined using SF763 glioma cell line. RESULTS: FABP7 was present in a unique population of glia in normal human brain, and its expression was increased in a subset of reactive astrocytes. FABP7 immunoreactivity in grade I pilocytic astrocytoma was predominantly cytoplasmic, whereas nuclear FABP7 was detected in other types of infiltrative glioma. Nuclear, not cytoplasmic, FABP7 immunoreactivity was associated with EGFR overexpression in GBM (N = 61, p = 0.008). Expression of the FABP7 gene in GBM also correlated with the abundance of EGFR mRNA in our previous microarray analyses (N = 34, p = 0.016) and an independent public microarray dataset (N = 28, p = 0.03). Compared to those negative for both markers, nuclear FABP7-positive/EGFR-positive and nuclear FABP7-positive/EGFR-negative GBM tumors demonstrated shortest survival, whereas those only positive for EGFR had intermediate survival. EGFR activation increased nuclear FABP7 immunoreactivity in a glioma cell line in vitro, and inhibition of FABP7 expression suppressed EGF-induced glioma-cell migration. Our data suggested that in EGFR-positive GBM the presence of nuclear FABP7 immunoreactivity increases the risk of poor prognosis CONCLUSION: In this study, we identified a possible mechanism as the basis of the association between nuclear FABP7 and poor prognosis of GBM. FABP7 expression can be found in all grades of astrocytoma, but neoplastic cells with nuclear FABP7 were only seen in infiltrative types of tumors. Nuclear FABP7 may be induced by EGFR activation to promote migration of GBM tumor cells. Positive nuclear FABP7 and EGFR overexpression correlated with short survival in EGFR-positive GBM patients. Therefore, nuclear FABP7 immunoreactivity could be used to monitor the progression of EGFR-overexpressed GBM

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery