Interactive contribution of hyperinsulinemia, hyperglycemia, and mammalian target of rapamycin signaling to valvular interstitial cell differentiation and matrix remodeling.

Diabetes and its major key determinants insulin resistance and hyperglycemia are known risk factors for calcific aortic valve disease (CAVD). The processes leading to molecular and structural alterations of the aortic valve are yet not fully understood. In previous studies, we could show that valvular interstitial cells (VIC) display canonical elements of classical insulin signaling and develop insulin resistance upon hyperinsulinemia and hyperglycemia accompanied by impaired glucose metabolism. Analyses of cultured VIC and aortic valve tissue revealed extracellular matrix remodeling and degenerative processes. Since PI3K signaling through mammalian target of rapamycin (mTOR) is involved in fibrotic processes of the heart, we aim at further functional investigation of this particular Akt-downstream signaling pathway in the context of diabetes-induced CAVD. Primary cultures of VIC were treated with hyperinsulinemia and hyperglycemia. Phosphorylation of mTOR(Ser2448) was determined by Western blot analysis after acute insulin stimulus. Inhibition of mTOR phosphorylation was performed by rapamycin. Phosphorylation of mTOR complex 1 (MTORC1) downstream substrates 4E-BP1(Thr37/46) and P70S6K(Thr389), and MTORC2 downstream substrate Akt(Ser473) as well as the PDK1-dependent phosphorylation of Akt(Thr308) was investigated. Markers for extracellular matrix remodeling, cell differentiation and degenerative changes were analyzed by Western blot analysis, semi-quantitative real-time PCR and colorimetric assays. Hyperinsulinemia and hyperglycemia lead to alterations of VIC activation, differentiation and matrix remodeling as well as to an abrogation of mTOR phosphorylation. Inhibition of mTOR signaling by rapamycin leads to a general downregulation of matrix molecules, but to an upregulation of α-smooth muscle actin expression and alkaline phosphatase activity. Comparison of expression patterns upon diabetic conditions and rapamycin treatment reveal a possible regulation of particular matrix components and key degeneration markers by MTORC1 downstream signaling. The present findings broaden the understanding of mitogenic signaling pathways in VIC triggered by hyperinsulinemia and hyperglycemia, supporting the quest for developing strategies of prevention and tailored treatment of CAVD in diabetic patients.

Airway management of congenital pulmonary airway malformation resection in neonates and infants: A case cohort study.

BACKGROUND: Anesthestic management of congenital pulmonary airway malformation has not been well described in the literature. It is not clear whether one-lung ventialtion is indicated during thoracoscopic lobectomy and if so, what is the best technique achieve it. AIMS: We describe the variables with the two commonly performed surgical techniques, thoracoscopic lobectomy and open thoracotomy, from our institutional database to assess the role of lung isolation and the preferable method of lung isolation technique for congenital pulmonary airway malformation resections. METHODS: After institutional review board approval, fetal center records were reviewed retrospectively from January 2010 to July 2016 for patients who underwent congenital pulmonary airway malformation resection. The primary goal was to describe the anesthesia induction-airway management techniques with emphasis on one-lung ventilation techniques. RESULTS: Among the 65 resections, one-lung ventilation was performed in 30 resections (46%) and was primarily achieved by endobronchial intubation in most cases (80%). One-lung ventilation was performed in a greater number of resections with thoracoscopic lobectomy (96%) compared to open thoracotomies. CONCLUSION: From our institution cohort, one-lung ventilation was more commonly used during thoracoscopic resections and was most commonly achieved with endobronchial intubation. Most patients were induced with inhalational anesthesia (sevoflurane), nondepolarizing neuromuscular blocker, and gentle positive pressure ventilation for intubation.

Improving on-time start of day and end of day for a pediatric surgical service.

BACKGROUND AND OBJECTIVE: In multicase pediatric ear, nose, and throat operating rooms (ORs), brief delays in early case start times often produce a cascading effect of lengthy delays by the end of the day and can often lead to patient, family, and staff dissatisfaction and increased labor costs due to unplanned overtime. We sought to improve actual end of day relative to scheduled end of day from 40% to 60%. METHODS: Key drivers of the process included case scheduling, ordering of sedative medications, and nurse availability in the post anesthesia care unit to receive the patient from the anesthesia provider. A multidisciplinary team conducted a series of tests of change addressing the various key drivers. Data were collected by using an independent, impartial data collector as well as being extracted from the hospital information technology system. Data were analyzed by using control charts and statistical process control methods. RESULTS: The percentage of ORs ending on time increased from 40% to 60%. Appropriate scheduling of complex cases increased from 10% to 87%, and accurate scheduling of case duration improved from 21% to 48%. Timely premedication increased from 55% to 90% and immediate availability of a nurse in the postanesthesia care unit from 68% to.90%. CONCLUSIONS: By applying quality-improvement methods, significant improvements were made in a multicase pediatric ear, nose, and throat OR. The impact can be significant by reducing wait times for patients, as well as staff overtime for the institution.

Getting started with the model for improvement: psychology and leadership in quality improvement.

Although the case for quality in hospitals is compelling, doctors are often uncertain how to achieve it. This article forms the third and final part of a series providing practical guidance on getting started with a first quality improvement project. Introduction.