Resident: Jack Melson, MD, Class of 2019
Faculty Mentor: Richard Hall, MD
Cancer is the second leading cause of death worldwide, and lung cancer is the leading cause of cancer related mortality. Large scale genomic analyses of lung cancer have revealed both the complexity of lung cancer genetics and commonly occurring molecular alterations that represent potential therapeutic targets and prognostic indicators. Targeted therapies have dramatically changed treatment for the subset of patients with actionable driver mutations. Immunotherapy with checkpoint inhibitors which disrupt the PD-1/PD-L1 interaction is an important emerging therapy for the broader population of patients with advanced non-small cell lung cancer who lack driver mutations or who have progressed on therapy. Genetic predictors of response to immunotherapy remain uncertain. One candidate is TP53, mutation of which is present in approximately 50% of lung adenocarcinomas. Several publications have suggested that TP53 mutation is positively associated with response to immunotherapy, possibly due to an associated increase in neoantigen expression. Our hypothesis is that non-small cell lung cancer (NSCLC) patients with a detectable TP53 mutation and treated with a checkpoint inhibitor-containing regimen at UVA will demonstrate a statistically significant increase in progression free survival compared to patients lacking TP53 mutations.
Resident: Kasey Little, MD, Class of 2019
Faculty Mentor: Andrew Parsons, MD
Health systems, payers, and patients are increasingly recognizing the need to reduce healthcare costs. “Value” is defined as the quotient of meaningful patient outcomes compared to the costs of care. Evidence shows that residency training influences physician ordering behavior and value-based decision making, and a joint AAIM-ACP committee as well as the ACGME have declared cost awareness an important priority for resident education. Additional research shows that providing cost data alone is insufficient—for it to have an effect on provider habits, it must also be accompanied by targeted education related to high value care. To fill this void of information for our residents, we are developing a cost-conscious care lecture series that asks residents to adequately diagnose and treat patients while ordering as few tests as possible.
Our hypothesis is that providing data about hospital charges in the context of case presentations will increase resident knowledge of healthcare costs and change attitudes toward cost-conscious care. We have collected pre-intervention data and plan to deliver cost-conscious care lectures including education on the scenario diagnosis as well as the utility and costs of tests ordered. This will be followed by repeat surveys for statistical comparison to pre-intervention data.
Resident: Thomas Dieringer, MD, Class of 2019
Faculty Mentor: Ann Hays, MD
Clostridium difficile infection remains one of the most commonly acquired nosocomial infections in the United States. These infections are responsible for billions of healthcare dollars spent each year and have been challenging to treat given their propensity for recurrence and reinfection in susceptible populations including infants, immunocompromised, and the elderly. Recently, fecal microbiota transplantation (FMT) has emerged as a new therapy to better address the growing need to manage severe and complicated recurrent clostridium difficile infections. Few studies have addressed the efficacy of this treatment, especially compared to standard therapies involving antibiotic tapers and supplementation with probiotics. We aim to review current the therapeutic options including FMT and alternatives including vancomycin tapering with probiotic supplementation in severe and complicated recurrent clostridium difficile infections at the University of Virginia. Our hypothesis is that patients with severe and complicated clostridium difficile infection treated with a prolonged vancomycin taper and probiotic supplementation with Kefir do not have a higher rate of recurrence or reinfection when compared to patients managed with fecal microbiota transplantation. Outcomes for different treatment and patient populations will be analyzed with chi-square or Fisher’s exact test. Bivariate logistic regression will be used to evaluate risk factors for clostridium difficile recurrence or reinfection.
Resident: Sumner Abraham, MD, Class of 2019
Faculty Mentor: Ryan Gentzler, MD
Immunotherapy (check-point inhibitors, CPIs) are now widely used in the treatment of both metastatic melanoma and non-small cell lung cancer (NSCLC). Brain metastases frequently occur and are treated with localized central nervous system (CNS) radiation therapy (RT). We have built a database patients treated at UVA with melanoma and NSCLC brain metastases treated with CNS-RT from 2011 to present. Given the mechanisms of action of both CPI and RT, there is likely to be a synergistic effect of these two therapies in catalyzing the immune system and its response. The exact nature of this interaction has not yet been elucidated, and there is minimal data on the side effect profile of using these two therapies in intracranial metastases from melanoma or NSCLC primaries. There is data to support the efficacy of these CPI therapies and their effectiveness in patients with NSCLC brain metastases, but combination with any kind of RT is not included in this data. While all data present shows improvement in OS, there is little to no data present as to the timing of adverse effects from these therapies that are likely due to an amplification of a patient’s immune response. Additionally, the variable timing of SRS in relation to systemic CPI therapy makes different definition of the study endpoints exceedingly difficulty to draw any valuable conclusions. Since both CNS-RT and CPIs can cause neuro-inflammation, our study is aiming to analyze clinical outcomes of patients treated with CPI therapy in combination with RT for patients with brain metastases from melanoma or NSCLC- specifically testing the hypothesis that concomitant treatment with CPIs and CNS-RT results in an increased risk of central nervous system adverse events.
Resident: Daniel Stein, MD, MPH, Class of 2017
Faculty Mentor: Stephen Caldwell, MD
Gastric varices are present in up to 25% of patients with cirrhosis, and form as a compensatory shunt to reduce blood flow through the portal vein. Bleeding is seen in around a third of patients in a 3-year period. My project is a retrospective review of all of the UVA experience with two methods for management of bleeding – cyanoacylate glue (superglue) injected directly into the vessel and an IR procedure call BRTO (balloon retrograde transvenous obliteration) involving embolization. We plan to compare both clinical outcomes and further delineate the rationale for choosing one procedure vs the other.
Resident: Eric Holland, MD,, Class of 2017
Faculty Mentor: J. Randall Moorman, MD
The incidence and impact of atrial fibrillation (AF), particularly new-onset AF, remains poorly characterized in critically ill patients. We hypothesize that new-onset AF is a poorly recognized condition and is associated with worse outcomes in the coronary care unit (CCU). Patients will be grouped into four main categories: No AF, known AF, new-onset AF, and undiagnosed new-onset AF. Categorization will be based on 12-lead electrocardiogram (ECG) reports, continuous ECG data, and diagnosis code. We will implement a novel heart rhythm pattern recognition technique developed at UVA to further aid in detecting AF. Multivariable analysis will be performed to investigate if new-onset AF, both diagnosed and undiagnosed, has any impact on LOS and mortality compared to known AF. Multiple other risk factors, including age, post-operative status, heart failure, valvular heart disease, sepsis, and other co-morbidities will be explored as possible contributing factors to new-onset AF.
Resident: Sean Fortier, MD, Class of 2017
Faculty Mentor: Borna Mehrad, MD
Progression of interstitial lung disease (ILD) is unpredictable. The ability to predict progression of disease and outcomes would help identify at-risk patients that may benefit from pre-emptive care. As of yet, there exists no clinical biomarker(s) to make such predictions and guide management in ILD. Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive disease that manifests as a triad of albinism, platelet storage defects, and development of ILD in early adulthood. As such, individuals with HPS represent a unique population to develop biomarkers for ILD that can be tested in other ILD populations. We hypothesize that subjects with HPS will display a combination of peripheral blood molecular biomarkers that correlate with the progression and outcome of ILD. To test this hypothesis, we will utilize our existing database of 68 HPS patients followed longitudinally (with data including PFTs, chest CTs, lab tests, and serial exams) and process aliquots of frozen plasma from these patients for measurement of candidate biomarkers described in the literature as correlating with ILD and other fibrotic diseases. Candidate biomarkers will then be analyzed individually and in combination for correlation with decline in pulmonary function test parameters and death.
Resident: Bryan Lawlor, MD, Class of 2017
Faculty Mentor: Sula Mazimba, MD, MPH
Renal insufficiency is common in patients with advanced heart failure and is a risk factor for higher morbidity and mortality. While left ventricular assist device (LVAD) implantation may provide hemodynamic support, LVAD recipients are at a high risk for post-operative renal insufficiency. Recent studies by Sandner et al. (2009) and Hasin et al. (2012) have demonstrated overall improvement in renal function with Sandner’s study showing an association with improved survival after continuous-flow LVAD implantation. Despite these encouraging results, both studies did demonstrate a trend that as patients were followed further out from LVAD implantation, their renal function began to worsen again. It is currently unclear how this decline in renal function impacts mortality outcomes. To further characterize changes in renal function after LVAD implantation and the effect on mortality outcomes, a retrospective cohort study will be conducted reviewing all patients at the University of Virginia Health System who underwent continuous-flow LVAD implantation with the Heartmate II device. Multivariate analysis will be conducted to determine significant predictors of developing improved and worsened renal function after implantation, including patients who require renal replacement therapy. Mortality at 1, 3, and 6 months will also be reported and multivariate analysis will similarly be conducted to determine significant predictors with attention to mortality in patients with preimplantation renal insufficiency, patients without improvement in renal function after LVAD implantation, and patients without sustained improvement in renal function.