Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. TB is typically diagnosed by analysis of sputum, which can be difficult and uncomfortable to produce, especially for those living with HIV and children. Improved means of case finding are essential for disease detection and control. Oral Swab Analysis (OSA) is an alternative processing method for detecting Mycobacterium tuberculosis (Mtb). Oral swabs can be collected easily from everyone, including those who have difficulty producing sputum, but OSA requires further optimization to reach the level of sensitivity of current sputum analysis methods. Over the past year I have been working with high capacity foam swabs to optimize processing methods for Mtb detection. Foam swabs collect more biomass and Mtb material but also greater amounts of Polymerase Chain Reaction (PCR) inhibitory material from the tongue. I explored various DNA extraction techniques to minimize the impact of inhibitors. The GeneXpert, a cartridge based nucleic acid amplification test, has yielded the most promising results. I have developed an optimized protocol that has improved the efficiency of the Xpert machine when tested with contrived foam swab eluates. I will validate my findings with a paired analysis between the current “gold-standard” of oral swabs, the Copan FloqSwab, and foam swabs, using clinical samples collected from TB patients by our collaborators in South Africa. I anticipate the foam swabs will detect a greater number of weakly-positive samples as well as yield stronger PCR signals than their FloqSwab pairs. The global burden of TB remains incredibly high and there is an urgent need for improved case finding methods. Diagnostics that are effective in the absence of symptoms, safe and implementable in low resource settings are of the utmost importance. This research has the potential to improve upon existing clinical testing and increase detection of TB disease worldwide.

There is growing evidence to suggest that the hormones estrogen and progesterone, influence pulmonary function with regard to lung disease. Cystic fibrosis is an autosomal recessive genetic disorder resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and whilst often thought to predominantly be a pulmonary disease, it affects nearly every organ system in the body. My research aims to study the cyclical variations of estrogen and progesterone, using the menstrual cycle as a medium for studying hormonal fluctuations to better understand how they impact pulmonary and gastrointestinal health. I also hope to investigate how these hormones affect the symptomatology of diseases in these organ systems. I will look at the mechanism of action of both these hormones, aiming to study how they interact with the regulation of and/or changes in gene expression. To organize and inform my research, I will be conducting an integrative literature review and examining data from a recent study by Dr. Godfrey’s team that sought to assess and track menstrual symptoms in women living with cystic fibrosis. I hypothesize that hormonal fluctuations, and increased hormone levels, may negatively affect overall organ system function and disease symptom severity; these outcomes would be exacerbated in cystic fibrosis pathology. I strive to understand the implications of these findings, and how they can contribute to informing ongoing research. With the advent of therapeutic modulators, the life expectancy for individuals with cystic fibrosis has significantly increased - warranting more extensive research into life course health outcomes and reproductive health. Women’s health is heavily underrepresented in research, and I sincerely hope to further my own learning through this opportunity.

Trauma is the 6th leading cause of mortality among Americans aging 65-79 years and outcomes after traumatic injury are worse among older patients. However, identifying which older adults will have worse outcomes after trauma is difficult. Frailty, an aging-related syndrome of physiological decline, has been associated with worse outcomes post traumatic injury. Most tools used to identify frailty rely on subjective data, which is often unattainable if patients are unconscious, delirious, or suffering from mental health illnesses. The aim of this study is to determine the utility of ultrasound and CT measurements of the masseter muscle (jaw muscle) in quantifying frailty by diagnosing sarcopenia, analyzing its correlation with clinical measures of frailty, and its association with geriatric patient outcomes after traumatic injury. Following IRB approval, I screen trauma patients for eligibility. Patients must be adults, have had a head CT taken in the last 24 hours, have no injury to the masseter muscle, and are able to answer questions about daily life activities. After obtaining consent, I interview to assess nutritional status and overall health using frailty questionnaires. Then, I perform a bedside ultrasonographic exam of the patients’ masseter muscle on both left and right sides. Lastly, I analyze the masseter muscle on the head CT scan. I measure the masseter’s width, depth, and cross-sectional area (CSA) using the Centricity Software. Our preliminary data shows that changes in masseter muscle size are detectible in radiological studies. I found that a representative patient’s masseter muscle width on ultrasound decreased by 29% eighteen days post trauma. Additionally, I collected four CT measurements on the same patient during their hospital stay: masseter muscle CSA decreased by 28% over 12 days and by 41% over 29 days. Results from this study regarding the association of masseter muscle size and frailty are still being analyzed. If significant, these measurements will allow for quick detection of frailty, allow physician to take appropriate treatment decisions, and improve patient outcomes.

Chronic recurrent multifocal osteomyelitis (CRMO) is an auto-inflammatory condition of unclear etiology. CRMO causes pain due to inflammation of bones and is typically diagnosed at 9 to 10 years of age. Depending on severity, the disease is treated with nonsteroidal anti-inflammatory drugs (NSAIDS), disease-modifying anti-rheumatic drugs (DMARDs), or tumor necrosis factor inhibitors (TNFi). Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of psoriatic arthritis, has shown efficacy even in DMARD-resistant disease while offering easier delivery than injectable or intravenous treatments. This case series presents four patients who were treated with tofacitinib for CRMO. In Case 1, a 13-year-old girl was started on tofacitinib 4 years after CRMO diagnosis, due to persistent bone disease and psoriasis despite use of biologic and bisphosphonate medications. Her CRMO was well-controlled at her most recent visit, 7 months after initiating tofacitinib. In Case 2, an 11-year old girl was started on tofacitinib 7 years after CRMO diagnosis, following failure of other treatments. Tofacitinib was discontinued after 4 months due to persistent CRMO symptoms. Case 3 is a patient who began tofacitinib treatment 9 years after disease onset, after having discontinued various biologics due to persistent bone and GI symptoms. An MRI taken 13 months after tofacitinib initiation showed no bone inflammation. In Case 4, a patient began tofacitinib monotherapy 2 years after his CRMO diagnosis. After 3 months of treatment, his Crohn’s disease, rash and bone pain improved, but an MRI showed worsening bone lesions for which he restarted bisphosphonate infusions. Of the four cases, two showed improvement in CRMO bone symptoms when transitioned to tofacitinib, while psoriasis remained stable. Tofacitinib is likely effective for less severe cases of CRMO. Because there are currently no FDA-approved medications for CRMO, a clinical trial assessing the efficacy of tofacitinib in children with CRMO is warranted.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with high risk of metastasis. Recent developments of PD-1/PD-L1 immunotherapy significantly improved treatment outcomes of metastatic MCC. While approximately half of patients respond to immunotherapy, the other half of the patients do not benefit. Thus, it has become increasingly important to identify factors that potentially impact immunotherapy response. Multiple studies in melanoma have demonstrated that patients who are older or have a higher body mass index (BMI) show better immunotherapy response. The purpose of this study is to explore the effects of age and/or BMI in MCC patients to immunotherapy response. I helped create a cohort of 183 patients who had undergone immunotherapy initially identified in a longitudinal single center registry. I then helped collect information about age and BMI at the start of immunotherapy along with other clinical features. Treatment response, disease-specific and overall survival were analyzed in 183 patients using cox regression and natural cubic spline models. During this process, I assisted in distinguishing the number of splines we would like to use for our analysis, as well as choosing the best model to accurately represent data for different variables. After adjusting for age, sex, and stage, BMI did not have significant impact on overall survival (p=1.0), objective response (p=0.5), or disease progression (p=0.8) while on immunotherapy. A nonlinear relationship between age and immunotherapy response was observed and showed potentially worse response to treatment in older patients. However, this was not statistically significant (p<0.1). Unlike prior studies in melanoma, we found that BMI does not have a significant impact on immunotherapy in MCC. Older age may have a negative impact on the response. This warrants additional research into the difference between melanoma and MCC to further elucidate mechanism of actions.

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer that presents with advanced disease in ~35% of cases and recurs in 40% after treatment. Immunotherapy (IMTX) with PD-1/PD-L1 inhibitors demonstrates an ~60% response rate in immunocompetent patients. Although patients with immunosuppression (IS) have a higher risk of developing MCC and worse prognosis than immunocompetent (IC) patients, the efficacy of IMTX in IS patients is not well understood because most clinical trials excluded them. This retrospective study aims to compare IMTX outcomes between IC and IS patients, and the relative impact of IS subtypes. In this project, I determined the cohort of 183 patients with advanced MCC who were treated with first-line IMTX from a Seattle-based data registry. I collected the following data from analyzing patients’ medical records: treatment response, immunosuppressive status, disease-specific and overall survival. I coordinated with the statisticians for Kaplan-Meier analyses of the data. The results show that IS patients had a 70% higher rate of disease progression compared to immunocompetent patients (p=0.04). IS patients also had worse overall survival outcomes (p<.01). Disease progression risk varied greatly among the different types of immunosuppression – patients with chronic lymphocytic leukemia had a higher risk of progression (HR=8.4, p<.01) compared to patients with other hematologic malignancies. While IMTX appears to be an effective treatment for MCC in IC patients, this is not the case for IS patients – research for new therapeutic options is needed for many IS patients with MCC. Additionally, this project highlights the importance of representation in research – many groups of patients are under-studied, and treatment efficacy is not well-characterized. Future studies should investigate IMTX outcomes in other under-studied groups, such as MCC patients of color.

Cutaneous graft-versus-host disease (cGVHD) is the leading cause of morbidity and mortality post-allogeneic hematopoietic cell transplantation (HCT). There is general uncertainty about the utility and safety of skin biopsy for diagnosing cGVHD in the early post-transplant period. In collaboration with UW Medicine and Mayo Clinic, I conducted a retrospective analysis of skin biopsies performed within 100 days post-HCT between 2000 and 2014. 740 biopsies from 602 patients (356 male, 256 female) were included in analysis. 87.1% (n=525) were white. The age range was 19-75y, with a mean of 50.3y. 456 (61.6%) skin biopsies were performed on inpatients, and 284 (38.3%) on outpatients. Only 8 (1.3%) patients had documented biopsy complications. The primary complication was excessive bleeding, which resolved after application of pressure bandage. Under the guidance of dermatopathologist Dr. Michi Shinohara, I conducted analyses to explore demographic and hematological features that may influence patient care or increase risk for biopsy complications. For example, on average, Hispanic patients received biopsies 8 days later following rash onset compared to their non-Hispanic counterparts. I am currently looking into clinical approach differences between Hispanic and non-Hispanic patients, such as complication documentation/assessment variability and presence of additional consultations. With respect to blood features, the mean neutrophil count was 0.228 K/µL and 2.98 K/µL and the mean platelet count was 18.7 K/µL and 100.6 K/µL for patients with and without biopsy complications, respectively. The complication rate for patients with either extremely low neutrophils (<0.11 K/µL) or platelets (<20 K/µL) was 5.3%. We conclude that skin biopsies performed in the immediate post-HCT period have a very low serious complication rate, even in patients with low cell counts. When skin biopsies are otherwise medically indicated in this patient population, concern regarding skin biopsy safety should not deter performance of this procedure in this patient population.