New STS ACSD risk models have generally excellent calibration and discrimination and are well suited for risk adjustment of STS performance metrics.

c-Myc protein stability and activity are tightly regulated by the ubiquitin-proteasome system. Aberrant stabilization of c-Myc contributes to many human cancers. c-Myc is ubiquitinated by SCF Fbw7 (a SKP1-cullin-1-F-box complex that contains the F-box and WD repeat domain-containing 7, Fbw7, as the F-box protein) and several other ubiquitin ligases, whereas it is deubiquitinated and stabilized by ubiquitin-specific protease (USP) 28. The bulk of c-Myc degradation appears to occur in the nucleolus. However, whether c-Myc is regulated by deubiquitination in the nucleolus is not known. Here, we report that the nucleolar deubiquitinating enzyme USP36 is a novel c-Myc deubiquitinase. USP36 interacts with and deubiquitinates c-Myc in cells and in vitro, leading to the stabilization of c-Myc. This USP36 regulation of c-Myc occurs in the nucleolus. Interestingly, USP36 interacts with the nucleolar Fbw7γ but not the nucleoplasmic Fbw7α. However, it abolished c-Myc degradation mediated both by Fbw7γ and by Fbw7α. Consistently, knockdown of USP36 reduces the levels of c-Myc and suppresses cell proliferation. We further show that USP36 itself is a c-Myc target gene, suggesting that USP36 and c-Myc form a positive feedback regulatory loop. High expression levels of USP36 are found in a subset of human breast and lung cancers. Altogether, these results identified USP36 as a crucial and bono fide deubiquitinating enzyme controlling c-Myc's nucleolar degradation pathway.c-Myc | USP36 | ubiquitination | deubiquitination | nucleolus

Completely new STS ACSD risk models have been developed based on contemporary patient data; their performance is superior to that of previous STS ACSD models.

Extracellular nanovesicles (ENV) released by many cells contain lipids, proteins, and nucleic acids that contribute to intercellular communication. ENVs have emerged as biomarkers and therapeutic targets but they have also been explored as drug delivery vehicles. However, for the latter application, clinical translation has been limited by low yield and inadequate targeting effects. ENV vectors with desired targeting properties can be produced from parental cells engineered to express membrane-bound targeting ligands, or they can be generated by fusion with targeting liposomes; however, neither approach has met clinical requirements. In this study, we demonstrate that mechanical extrusion of approximately 10 cells grafted with lipidated ligands can generate cancer cell-targeting ENV and can be prepared in approximately 1 hour. This rapid and economic approach could pave the way for clinical implementation in the future. A new and rapid method for production of drug-targeting nanovesicles has implications for cancer treatment by chimeric antigen receptor T cells and other therapies. .

WHAT'S KNOWN ON THIS SUBJECT: Congenital heart disease is known to be a commonly treated and resource-intense condition across children' s hospitals, yet knowledge regarding the degree of cost variation across hospitals and associated factors is lacking.WHAT THIS STUDY ADDS: Using a linked clinical and administrative data set, we establish benchmarks for hospital costs for common congenital heart operations, and demonstrate wide variation in cost between hospitals related in part to differences in length of stay and complications. abstract BACKGROUND: A better understanding of costs associated with common and resource-intense conditions such as congenital heart disease has become increasingly important as children' s hospitals face growing pressure to both improve quality and reduce costs. We linked clinical information from a large registry with resource utilization data from an administrative data set to describe costs for common congenital cardiac operations and assess variation across hospitals. METHODS:Using linked data from The Society of Thoracic Surgeons and Pediatric Health Information Systems Databases (2006Databases ( -2010, estimated costs/case for 9 operations of varying complexity were calculated. Between-hospital variation in cost and associated factors were assessed by using Bayesian methods, adjusting for important patient characteristics. RESULTS:Of 12 718 operations (27 hospitals) included, median cost/ case increased with operation complexity (atrial septal defect repair, [$25 499] to Norwood operation, [$165 168]). Significant betweenhospital variation (up to ninefold) in adjusted cost was observed across operations. Differences in length of stay (LOS) and complication rates explained an average of 28% of between-hospital cost variation. For the Norwood operation, high versus low cost hospitals had an average LOS of 50.8 vs 31.8 days and a major complication rate of 50% vs 25.3%. High volume hospitals had lower costs for the most complex operations.CONCLUSIONS: This study establishes benchmarks for hospital costs for common congenital heart operations and demonstrates wide variability across hospitals related in part to differences in LOS and complication rates. These data may be useful in designing initiatives aimed at both improving quality of care and reducing cost. Pediatrics 2014;133:e553-e560 AUTHORS:

STS has developed an MVRR composite performance measure that will be used for participant feedback, quality performance assessment and improvement, and voluntary public reporting.

Objectives Analyses of mechanical circulatory support (MCS) in pediatric heart surgery have primarily focused on single-center outcomes or narrow applications. We describe patterns of use, patient characteristics, and MCS-associated outcomes across a large multicenter cohort. Methods Patients (<18yrs) in the STS Congenital Heart Surgery Database (2000-2010) were included. Characteristics and outcomes of those receiving post-operative MCS were described, and Bayesian hierarchical models were used to examine variation in adjusted MCS rates across institutions. Results Of 96,596 operations (80 centers), MCS was used in 2.4%. MCS patients were younger (13d v. 195d, p<0.0001) and more often had STS-defined preoperative risk factors (57.2% v. 32.7%, p<0.0001). Operations with the highest MCS rates included the Norwood procedure (17%) and complex biventricular repairs (arterial switch/VSD/arch repair-14%). Over half of MCS patients (53.2%) did not survive to hospital discharge (vs. 2.9%, non-MCS patients, p<0.0001). MCS-associated mortality was highest for truncus arteriosus and Ross-Konno operations (both 71%). Hospital-level MCS rates adjusted for patient characteristics and case mix varied by 15-fold across institutions; both high and low volume hospitals had substantial variation in MCS rates. Conclusion Perioperative MCS use varies widely across centers. MCS rates are highest overall for the Norwood procedure and complex biventricular repairs. Although MCS can be a life-saving therapy, over half of MCS patients do not survive to hospital discharge with mortality >70% for some operations. Future studies aimed at better understanding appropriate indications, optimal timing, and management of MCS may help to reduce variation in MCS across hospitals and improve outcomes.

No abstract