Early-stage melanoma, squamous and basal cell carcinomas have local control rates of >90% with wide excision after pathologically clear margins and >95% with Mohs micrographic surgery. Local control rates for these approaches are not well defined in Merkel cell carcinoma (MCC). Herein, we analyzed data from 80 patients (pts) in a Seattle-based IRB-approved registry who had local MCC and underwent surgical excision with pathologically clear margins. Patients who had local radiation therapy after surgery were excluded as radiation affects recurrence rate independent of surgery. We also performed meta-analysis of 13 published studies (846 pts) based on a random-effects model. For the 80 pt cohort, local recurrence rate (LRR; ≤2 cm from the primary tumor) was 10%. In-transit recurrence rate (ITR; >2cm from primary) was 1%. Regional nodal recurrence rate (RRR) was 5%. This cohort had low-risk characteristics with small primary tumors (74% were ≤1 cm, 23% were 1-2, and 4% were >2 cm). No residual tumor was found in 60% of re-excisions while 29% had closest pathologic margins <1 cm. Meta-analysis of 9 published studies (745 pts) who underwent excision with clear pathological margins yielded 16.4% LRR [95% CI 8.3-26.5], 9.5% ITR [95% CI 5.4-14.6], and 32.1% RRR [95% CI 19.1-46.7]. Data from 4 studies (101 pts) who underwent Mohs yielded 3.6% LRR [95% CI 0-16.3], 12.8% ITR [95% CI 6.4-21.1], and 20.7% RRR [95% CI 13.8-38.3]. In each cohort, LRR/IRR following surgical excision with pathologically clear margins was >10%. This suggests MCC is more likely to recur near the excision site than other skin cancers and may reflect biological difference in the MCC local extension pattern (discontinuous spread beyond pathologically clear margins). Even for pathologically negative excisions, higher risk tumors may benefit from adjuvant radiotherapy.

Merkel cell carcinoma (MCC) is a rare skin cancer with a high propensity for recurrence. Persons with chronic immunosuppression have a higher risk of developing MCC and a more aggressive disease course. Immunotherapy treatment enhances the immune system’s ability to fight MCC and is associated with improved disease-specific survival. However, the immunotherapy efficacy in immunosuppressed MCC patients is not well categorized. This study explores and aims to compare differences in immunotherapy efficacy between different forms of immunosuppression, and between immunocompetent versus immunosuppressed MCC patients. In this project, I determined the patient cohort from a Seattle-based prospective registry of 1,529 MCC patients and identified 36 patients treated with immunotherapy and who had chronic immunosuppression. I collected treatment response data from medical records, and analyzed the results. Of the 36 patients, 13 patients (36%) had a complete response (CR), 3 patients (8%) had a partial response (PR), and 20 patients (56%) had progressive disease (PD). Disease progression and survival status varied greatly among different types of immunosuppression. Five types of chronic immunosuppression were represented in these 36 patients and were evaluated for an objective response (CR or PR): chronic lymphocytic leukemia (CLL, 3/13, 23%), autoimmune disorders (AD, 3/9, 33%), solid organ transplant (SOT, 2/4, 50%), HIV/AIDs (2/3, 67%), and other hematologic malignancies (OHM, 6/7, 86%). In comparison, in a study of immunocompetent patients, 28 of 50 (56%) had objective responses to immunotherapy. Toxicities were also high in immunosuppressed patients, as 9/36 (25%) patients stopped treatment due to toxicities. Immunotherapy efficacy in patients with chronic immunosuppression appears to be dependent on the type of immunosuppression. While there is reason for optimism for patients with certain types of immunosuppression, MCC treatment for patients with CLL remains a major concern.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high (20%) rate of distant metastases, 80 percent of which occur within 2 years of diagnosis. Metastatic MCC (mMCC) to the heart is rare and presents a management challenge. Our systematic literature review revealed only 11 cardiac mMCC case reports. Most (n=6) patients received chemotherapy which is now known to lack durable response in MCC, and 2 received no treatment due to advanced disease and comorbidities. Hence, to better understand cardiac mMCC we queried an MCC data repository of patients diagnosed between 2011-2021. Progression-free survival (PFS) was measured from date of cardiac mMCC to progression or death. Among 582 MCC patients with distant metastases, 9 developed cardiac mMCC. Median age at initial MCC diagnosis (stage I (1), stage III (6), stage IV (2)) was 69 years. Most (n=8) patients  developed mMCC to the right atrium, except for 1 patient (initial stage pIIIA) who had metastasis to the left atrium. Treatment for cardiac mMCC varied: 5 patients received immunotherapy combined with radiotherapy, while the reminder received immunotherapy alone, somatostatin analog, or chemotherapy. Five patients had a complete response in the cardiac lesion after immunotherapy, with or without radiotherapy. Median PFS and overall survival (OS) was 114 and 325 days, respectively. To explore whether presence of cardiac mMCC impacts OS, we matched cardiac mMCC patients to non-cardiac mMCC patients by age, sex, stage, immunosuppression status, and number of prior metastatic episodes. Using Kaplan-Meier statistical analysis, we found no difference in OS for the matched cohort (p=0.96). Taken together, these data indicate the emerging role of immunotherapy and radiotherapy in controlling cardiac mMCC. Furthermore, the location of mMCC to the heart does not appear to confer a worse prognosis compared to non-cardiac sites.

Globally, about 10% of people living with HIV (PLHIV) also have concurrent Hepatitis B virus (HBV) infection. Without routine screening for HBV, the choice of antiretroviral therapy can be more difficult to manage, as not all medications treat both infections. The objective of this research was to identify risk factors that put PLHIV at higher risk of HBV infection. We conducted a prospective clinic-based study from 2013 – 2017 in Durban, South Africa. Participants were enrolled into the study if they tested positive for HIV, and all PLHIV were tested for HBV after enrollment. Follow up assessments were conducted at 3, 6, and 12 months after enrollment. Patients completed questionaries pertaining to sociodemographic status, medical history, clinical symptoms and mental health at each visit. I compared prevalence of HBV between age groups using a T-test. Univariate and multivariate logistic regression models were conducted on co-variates of the data set using the ‘dplyr’ and ‘stats’ packages in R. I measured adjusted odds ratios (aORs) for each covariate to compare risk factors for those with HBV and HIV compared to PLHIV. A total of 3105 PLHIV were enrolled, with a mean age of 33 years and 43% (n=1331) male. Of those, 196 (6%) individuals tested positive for HBV, with a mean age of 33 years and 62% (n=121) male. Participants aged >25, who were born before South Africa implemented routine infant vaccination for HBV in 1995, were more likely to have HBV (p=0.043). HBV diagnosis was associated with drinking alcohol over the past year (aOR = 1.17), lack of condom use (aOR = 1.10), and income >10,000 ZAR/month (aOR = 1.63). Implementing routine HBV testing for adults born before 1995 can help prevent the further increase of HBV infection rates. These study findings also provide additional support for enhanced HBV screening among PLHIV.

Aerial surveys are a tool commonly used to estimate population abundance for many species, yet little is known about how aircraft presence impacts animal behavior. The National Oceanic and Atmospheric Administration (NOAA) periodically conducts surveys in the U. S. waters of Alaska to monitor Arctic seal populations. These surveys are important as trends show reductions in the sea ice that these pinniped species depend on. Quantification of ringed seal (Pusa hispida) and bearded seal (Erignathus barbatus) rates of flushing from the sea ice into the water in response to aircraft overflights is necessary to strengthen population estimates and implement sound policy measures for activities in Alaska that may impact these pinnipeds. In the spring of 2021, NOAA conducted aerial surveys over the sea-ice of the Beaufort Sea. As an intern I separated the video into trials that captured seals before, during, and after the plane passed overhead. For each individual seal I then recorded species, weather, group size, distance from the plane, and seal behavior changes and geographic locations and analyzed which factors influence seal flushing behavior. In 161 trials, we recorded 266 ringed seals and 21 bearded seals. Only one bearded seal flushed (4.8%) while 47.8% of all ringed seals flushed. Most ringed seals flushed before the plane passed overhead. Generalized linear models indicated that distance from flight path and group size exerted the greatest influence on flushing behavior while weather and plane altitude were less important. Less distance from the flight path and larger group sizes led to higher ringed seal flushing rates. Understanding ice seal behavior will improve population estimates in future surveys. Overall flushing rates are important indicators of the disturbance ringed and bearded seals experience as a result of commercial and scientific activity in the Arctic and may be useful for permitting processes.

Cement is a large contributor to carbon dioxide (CO₂) emissions, and there is ongoing research to reduce this impact. The negative impact of carbon dioxide emissions on our atmosphere is a growing concern, so finding avenues to reduce such pollution is constantly sought after. Namely, studies have been conducted to explore the inclusion of natural fibers into the cement matrix, both cellulose-based and pure cellulose. For this reason, sustainable cement composites with mechanical performance comparable to ordinary cement are of interest. Cellulose has been proven to enhance mechanical compressive properties under certain processing conditions. Additionally, concrete is limited in applications due to its inherently weak tensile/flexural properties; to combat this, fiber reinforcements (often steel) are incorporated. Here, we compare the effects of different types of cellulose fibers as fillers in cement, specifically the effects in density, viscosity, and compressive strength. We used cellulose microfibers as well as nanofibers, with substantially different degrees of crystallinity and aspect ratios. Overall, the mechanical performance of mixtures produced with varying amounts of cellulose micro- and nan-fibers as well as varying water content were studied. We correlated the changes in viscosity, micromorphology, and compressive strength to rationalize the effects. Utilizing readily available natural fibers in the cement matrix will enhance the tensile properties of concrete structures while also reducing the harmful carbon dioxide emissions due to cement production.