Future of Leadership in Healthcare: Enabling Complexity Dynamics Across Levels

Healthcare is one of the world\u27s fastest-growing industries with over $10 trillion in projected spending by 2022 (Deloitte, 2019). Despite this growth, the industry faces several challenges including rising costs, care delivery outside urban areas and to marginalized populations, digital transformation, and regulatory compliance. To navigate these challenges and capitalize on growth opportunities, leaders must build and manage complex dynamics occurring in the space between the organization and a wide range of internal and external stakeholders. In this symposium, we address this issue by assembling a group of scholars trained in healthcare management, strategy, leadership, and organizational theory to discuss the role of leaders in the future of healthcare. Through a series of presentations, we will illustrate how leaders in healthcare enable complexity dynamics across organizational levels to drive desired outcomes. In doing so, we bring to the forefront the multilevel and complex nature of healthcare leadership and invite innovative thinking about leadership for the future of healthcare. Building Extra-Organizational Adaptive Networks: Complexity Leadership in Healthcare Presenter: Erin Bass; U. of Nebraska, Omaha Presenter: Ivana Milosevic; College of Charleston Physician CEOs & Patient Safety Presenter: Geoffrey Silvera; Auburn U. Presenter: Timothy J. Vogus; Vanderbilt U. Presenter: Jonathan Clark; U. of Texas At San Antonio Management Practices of Under-Resourced Nursing Homes Presenter: Justin Lord; Louisiana State U. Shreveport Stitching Ties: Team Performance in the Connected Organization Presenter: John Hollingsworth; U. of Michigan Presenter: Jason Owen-Smith; U. of Michigan, Ann Arbor Presenter: Dennie Kim; U. of Virginia Darden School of Business Presenter: Marlon DeMarcie Twyman; U. of Southern California, Annenberg School for Communication and Journalism Identifying Healthcare\u27s Future Leaders: Development of a Leadership Potential Model for Healthcare Presenter: Kevin S. Groves; Pepperdine U. Presenter: Ann E. Feyerherm; Pepperdine Graziadio Business Schoo

Sensitivity of MRI Tumor Biomarkers to VEGFR Inhibitor Therapy in an Orthotopic Mouse Glioma Model

MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI) and a slight decrease in the water apparent diffusion coefficient (ADC) were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV), relative microvascular blood volume (rMBV), transverse relaxation time (T2), blood vessel permeability (Ktrans), and extravascular-extracellular space (νe). The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Feasibility of Intracoronary GLP-1 Eluting CellBead (TM) Infusion in Acute Myocardial Infarction

Cell therapy is a field of growing interest in the prevention of post acute myocardial infarction (AMI) heart failure. Stem cell retention upon local delivery to the heart, however, is still unsatisfactory. Cell Beads were recently developed as a potential solution to this problem. Cell Beads are 170-mu m alginate microspheres that contain mesenchymal stem cells (MSCs) genetically modified to express glucagon-like peptide-1 (GLP-1) supplementary to inherent paracrine factors. GLP-1 is an incretin hormone that has both antiapoptotic and cardioprotective effects. Transplanting Cell Beads in the post-AMI heart might induce cardiomyocyte salvage and ultimately abrogate adverse cardiac remodeling. We aimed to investigate the feasibility of intracoronary infusion of Cell Beads in a large animal model of AMI. Four pigs were used in a pilot study to assess the maximal safe dose of CellBeads. In the remaining 21 animals, an AMI was induced by balloon occlusion of the left circumflex coronary artery for 90 min. During reperfusion, 60,000 CellBeads (n=11), control beads (n=4), or lactated Ringers' (n=6) were infused. Animals were sacrificed after 2 or 7 days, and the hearts were excised for histological analyses. Intracoronary infusion did not permanently affect coronary flow in any of the groups. Histological analysis revealed CellBeads containing viable MSCs up to 7 days. Viability and activity of the MSCs was confirmed by qPCR analysis that showed expression of recombinant GLP-1 and human genes after 2 and 7 days. CellBeads reduced inflammatory infiltration by 29% (p = 0.001). In addition, they decreased the extent of apoptosis by 25% (p = 0.001) after 2 days. We show that intracoronary infusion of 5 million encapsulated MSCs is safe and feasible. Also, several parameters indicate that the cells have paracrine effects, suggesting a potential therapeutic benefit of this new approach

Diagnosis of chronic thromboembolic pulmonary hypertension: A Canadian Thoracic Society clinical practice guideline update

status: publishe