Neurologic Dysfunction and Neuroprotection in Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) is a fast-growing procedure. Expanding to low-risk patients, it has surpassed surgical aortic valve implantation in frequency and has been associated with excellent outcomes. Stroke is a devastating complication after transcatheter aortic valve implantation. Silent brain infarcts identified by diffusion-weighted magnetic resonance imaging are present in most patients following TAVI. Postoperative delirium and cognitive dysfunction are common neurologic complications. The stroke and silent brain infarcts are likely caused by particulate emboli released during the procedure. Intravascularly positioned cerebral embolic protection devices are designed to prevent debris from entering the aortic arch vessels to avoid stroke. Despite promising design, randomized clinical trials have not demonstrated a reduction in stroke in patients receiving cerebral embolic protection devices. Similarly, the association of cerebral embolic protection devices with silent brain infarcts, postoperative delirium, and cognitive dysfunction is uncertain. Monitored anesthesia care or conscious sedation is as safe as general anesthesia and is associated with lower cost, but different anesthetic techniques have not been shown to decrease stroke risk, postoperative delirium, or cognitive dysfunction. Anesthesiologists play important roles in providing perioperative care including management of neurologic events in patients undergoing TAVI. Large randomized clinical trials are needed that focus on the correlation between perioperative interventions and neurologic outcomes.

Academic Productivity of US Neurosurgery Residents as Measured by H-Index: Program Ranking with Correlation to Faculty Productivity.

Engagement in research and academic productivity are crucial components in the training of a neurosurgeon. This process typically begins in residency training. In this study, we analyzed individual resident productivity as it correlated to publications across all Accreditation Council for Graduate Medical Education (ACGME)-accredited neurosurgery training programs in an attempt to identify how programs have developed and fostered a research culture and environment. We obtained a list of current neurosurgery residents in ACGME-accredited programs from the American Association of Neurological Surgeons database. An expanded PubMed and Scopus search was conducted for each resident through the present time. We tabulated all articles attributed to each resident. We then categorized the publications based on each neurosurgical subspecialty while in residency. A spreadsheet-based statistical analysis was performed. This formulated the average number of resident articles, h-indices, and most common subspecialty categories by training program. We analyzed 1352 current neurosurgery residents in 105 programs. There were a total of 10 645 publications, of which 3985 were resident first-author publications during the period of study. The most common subspecialties among all resident publications were vascular (24.9%), spine (16.9%), oncology (16.1%), pediatric (5.6%), functional (4.9%), and trauma (3.8%). The average resident published 2.9 first-author papers with average of 38.0 first-author publications by total residents at each program (range 0-241). The average h-index per resident is 2.47 ± 3.25. When comparing previously published faculty h-index program rankings against our resident h-index rankings, there is a strong correlation between the 2 datasets with a clear delineation between Top-20 productivity and that of other programs (average h-index 4.2 vs 1.7, respectively, P < .001). Increasing program size leads to a clear increase in academic productivity on both the resident and faculty level (average h-index 1.6, 1.9, 3.9 for 1, 2, and 3 resident per year programs, respectively, P < .001). Resident first-author publications correlated with recently described academic departmental productivity. Subspecialty resident publications are highest in cerebrovascular surgery. Resident research and publication is a key metric for assessing the productivity of academic neurosurgery programs and is consistent with one of the core foci of neurosurgical training.

Adiponectin regulates bone mass via opposite central and peripheral mechanisms through FoxO1.

The synthesis of adiponectin, an adipokine with ill-defined functions in animals fed a normal diet, is enhanced by the osteoblast-derived hormone osteocalcin. Here we show that adiponectin signals back in osteoblasts to hamper their proliferation and favor their apoptosis, altogether decreasing bone mass and circulating osteocalcin levels. Adiponectin fulfills these functions, independently of its known receptors and signaling pathways, by decreasing FoxO1 activity in a PI3-kinase-dependent manner. Over time, however, these local effects are masked because adiponectin signals in neurons of the locus coeruleus, also through FoxO1, to decrease the sympathetic tone, thereby increasing bone mass and decreasing energy expenditure. This study reveals that adiponectin has the unusual ability to regulate the same function in two opposite manners depending on where it acts and that it opposes, partially, leptin's influence on the sympathetic nervous system. It also proposes that adiponectin regulation of bone mass occurs through a PI3-kinase-FoxO1 pathway.

Genetic determination of the cellular basis of the sympathetic regulation of bone mass accrual.

The sympathetic nervous system, whose activity is regulated by leptin signaling in the brain, is a major regulator of bone mass accrual. To determine the identity of the cell type in which the sympathetic tone signals to inhibit bone mass accrual, we performed a systematic, cell-specific analysis of the function of the ß2 adrenergic receptor (Adrß2) and various genes implicated in the pathway in the mouse. This was followed by leptin intracerebroventricular (ICV) infusion and bone histomorphometric analyses of bone parameters. We show that the sympathetic tone signals in the osteoblasts to inhibit CREB (cAMP-responsive element-binding protein) phosphorylation and thus decrease osteoblast proliferation and to promote ATF4 phosphorylation and thus increase RANKL (receptor activator of NF-κB ligand) expression, which then stimulates osteoclast differentiation. Leptin ICV infusion in various mouse models established that leptin-dependent inhibition of bone mass accrual relies on both transcriptional events taking place in osteoblasts. Thus, this study formally identifies the osteoblast as the major cell type in which the molecular events triggered by the sympathetic regulation of bone mass accrual take place. As such, it suggests that inhibiting sympathetic signaling could be beneficial in the treatment of low bone mass conditions.