University of Nebraska Medical Center
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Virtual Versus Dye Chromoendoscopy in Dysplasia Detection in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
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A Comparison of Scar Infiltration, Scar Deactivation, and Standard of Care for Treatment of Chronic, Post-Surgical Pain After Cesarean Section in the Primary Setting: A Comparative Effectiveness Trial
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Sustained Positive Buprenorphine After Long-Acting Injectables and Transition to Naltrexone With a Novel Micro-Dosing Approach in Treating Opioid Use Disorder: A Case Report
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Improving the Usability and Usage of a Tracheostomy Order Set
Get PDFEducational Objectives: At the conclusion of this presentation, the participants should be able to (a) understand the benefits of simplifying EMR order-sets; (b) simplify a commonly used procedure or order set which includes identifying stakeholders who should contribute to the discussions; (c) identify and overcome barriers that would inhibit implementation and efficiency Objectives: Usability of electronic medical records has been linked to concerns for patient safety and provider wellness. One concern is that an order set’s “end user” may be inexperienced with the complexities associated with the tracheostomy patient continuum. The formation and utility of an intuitive workflow in the entire care continuum has not been investigated. This quality improvement project aimed to (a) Improve order set usability; (b) Create a multidisciplinary process to overhaul a clinical order set at a single institution with stakeholder engagement across service lines; (c) Address barriers to implementation and dissemination with processes and stakeholder groups. Study design: A quality improvement project focused on the multidisciplinary creation and analysis of the impact of simplification on a process within the EMR at a single institution. Methods The workflow of a self-organized multidisciplinary working group was documented and end users were identified. An implementation plan was crafted and use was tracked. Special attention was made to unintended consequences. Results Six multidisciplinary meetings took place. Each meeting included suggestions for improvements and discussions regarding the impact of each change on the many stakeholders. We found opportunity to defer practice to hospital policy. We also found opportunity to remove education from the order set. Feedback and analyses from this intervention revealed improved efficiency with 42% fewer clicks and 60% fewer clinical decisions required for completion of the order set. More importantly, residents at both the junior and senior levels commented that the increased simplicity and efficiency has improved workflow during times when they are on call and most fatigued. Barriers to implementation included some hospitals within the system not wishing to move forward and turnover of end users in an academic institution. Conclusion Assembling a multidisciplinary team to improve the usability of a tracheostomy order set provides an opportunity for seamless implementation of hospital policies across service lines. This may be a generalizable pathway to a standardized care continuum without a dedicated tracheostomy team.https://digitalcommons.unmc.edu/com_otolayrn_pres/1001/thumbnail.jp
Demystifying Tumor-Mediated Local and Systemic Immunosuppression in Pancreatic Ductal Adenocarcinoma
Get PDFPancreatic ductal adenocarcinoma (PDAC) is a deadly disease that costs many lives every year. Immense immunosuppression at local primary and metastasis sites, as well as the systemic organism, is a hallmark of PDAC that seems a hurdle too insurmountable to overcome. The tumor microenvironment (TME) is characterized by an abundance of anti-inflammatory cytokines, suppressive immune cells, and a hypoxic milieu that renders effector immune cells inactive and fosters further development of immunosuppression. Chapter 1 of this dissertation presents in detail the components that characterize this immunosuppression in the TME as well as within the systemic immunological organs.
The spleen, one of the most important organs for the development and maintenance of a healthy, well-functioning immune system, holds particular significance in PDAC due to its close proximity to the developing tumor. Historically seen as a place for lymphocyte activation and generation of an inflammatory response to infection and malignancy, we have found evidence that the spleen can also be home to immunosuppressive cell types, further contributing to an impaired anti-tumor immune response. Our findings of a tolerogenic, IDO-1-expressing dendritic cell (DC) subtype in the spleen of PDAC patients that stands in vivid communication networks with a plethora of other immune cells are delineated in Chapter 2. This novel splenic DC subset warrants further investigation to parse out the biological significance of the strong interactions between the DCs and other immune cells that potentially are the cause and effect of tumor-derived immunosuppression at the same time.
The main body of work of this dissertation’s projects is presented in Chapters 3 and 4, thoroughly and broadly investigating the influence of tumor cell-derived extracellular vesicles (EVs) on immune cells in PDAC. It has long been known that tumor cells secrete EVs to extend pro-tumoral communication networks within the body and promote tumor progression and metastasis. However, the effects on immune cells, in particular, are understudied. The work presented here is novel, more extensive than ever before, and most certainly essential to deepening our and the field’s understanding of tumor-derived immune-regulating factors in PDAC. We have deciphered the influence of PDAC-derived EVs on the humoral and cellular immune system, with particular emphasis on the role of tumor marker MUC1 on EVs (Chapter 3). Murine PDAC cells (KPC7107), which express MUC1, secrete EVs with strong immunosuppressive effects, whereas EVs from cells lacking MUC1 stimulate the immune system instead. MUC1+ EVs are the tumor’s malicious and sneaky messengers, spreading throughout the body and impacting aspects of the adaptive immune system, ranging from antigen presentation to lymphocyte exhaustion to germinal center formation.
We expanded our investigations (1) to study additional immune cell subtypes more thoroughly and, most importantly, (2) to include patient-derived EVs (as described in the last chapter of this thesis). These investigations are just a starting point for future research but significantly elevate the “translationability” and clinical importance of our work. The influence of EVs on NK cells shows a clear immunosuppressive effect on NK cell killing ability in cancer. Initial investigations of marker expression on patient-derived EVs suggest a role of Fas-mediated apoptosis pathways in EV-mediated immunosuppression and propose a relationship between MUC1 and FasR expression on EVs. Most importantly, identifying patient-specific variables in primary samples and clearly defining and delineating heterogeneity in EV composition and effects is essential for ever having even the slightest chance of winning the battle over PDAC.
The following chapters describe in detail the majority of the work that has been done by me in the past five-ish years in the Hollingsworth laboratory. It is a lot for me, a lot for our laboratory, but just so little of what will need to come next. It is humbling and exciting at the same time to think about what this data represents and how many million doors it opens for the future. Let’s start