Chemosensory deficits are best predictor of serologic response among individuals infected with SARS-CoV-2.

OBJECTIVE: Smell and taste alteration are closely linked to infection with SARS-CoV-2 and may be associated with a more indolent disease course. Serologic response rates among individuals with mild disease remains limited. We sought to identify whether chemosensory changes associated with COVID-19 were predictive of a serologic response. STUDY DESIGN: Cross-sectional study. METHODS: The sample consisted of 306 adults (≥18 years old) volunteering for convalescent plasma donation following perceived COVID-19 illness from April-June 2020. Documentation of COVID-19 PCR status, clinical symptoms at time of illness, and treatment course occurred at the time of serologic analysis, where we assessed chemosensory function using patient-perceived deficits. We implemented previously validated ELISA screening to determine serologic status regarding anti-Spike immunoglobulins. Statistical analysis using stepwise logistic models were employed to identify predictive factors of serologic response. RESULTS: Of 306 patients undergoing serologic and chemosensory evaluation, 196 (64.1%) and 195 (63.7%) reported subjective olfactory and taste dysfunction, respectively, during the first two weeks of COVID-19 infection. In unadjusted models, the odds of developing suprathreshold IgG antibody titers were 1.98 times higher among those who reported altered smell (95% CI 1.14-3.42, p = 0.014) and 2.02 times higher among those with altered taste (95% CI 1.17-3.48, p = 0.011) compared to those with normal smell and taste. Multivariable logistic models adjusting for sex, age, race/ethnicity, symptom duration, smoking status and comorbidities index demonstrated that altered smell and taste remained significant predictors of positive anti-spike IgG response (smell OR = 1.90, 95% CI 1.05-3.44, p = 0.033; taste OR = 2.01, 95% CI = 1.12-3.61, p = 0.019). CONCLUSION: Subjective chemosensory dysfunction, as self-reported smell or taste deficiency, is highly predictive of serologic response following SARS-CoV-2 infection. This information may be useful for patient counseling. Additional longitudinal research should be performed to better understand the onset and duration of the serologic response in these patients.

Neoadjuvant chemoradiation alters the immune microenvironment in pancreatic ductal adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma (PDAC) have a grim prognosis despite complete surgical resection and intense systemic therapies. While immunotherapies have been beneficial with many different types of solid tumors, they have almost uniformly failed in the treatment of PDAC. Understanding how therapies affect the tumor immune microenvironment (TIME) can provide insights for the development of strategies to treat PDAC. We used quantitative multiplexed immunofluorescence (qmIF) quantitative spatial analysis (qSA), and immunogenomic (IG) analysis to analyze formalin-fixed paraffin embedded (FFPE) primary tumor specimens from 44 patients with PDAC including 18 treated with neoadjuvant chemoradiation (CRT) and 26 patients receiving no treatment (NT) and compared them with tissues from 40 treatment-naïve melanoma patients. We find that relative to NT tumors, CD3+ T cell infiltration was increased in CRT treated tumors (p = .0006), including increases in CD3+CD8+ cytotoxic T cells (CTLs, p = .0079), CD3+CD4+FOXP3- T helper cells (Th, p = .0010), and CD3+CD4+FOXP3+ regulatory T cells (Tregs, p = .0089) with no difference in CD68+ macrophages. IG analysis from micro-dissected tissues indicated overexpression of genes involved in antigen presentation, T cell activation, and inflammation in CRT treated tumors. Among treated patients, a higher ratio of Tregs to total T cells was associated with shorter survival time (p = .0121). Despite comparable levels of infiltrating T cells in CRT PDACs to melanoma, PDACs displayed distinct spatial profiles with less T cell clustering as defined by nearest neighbor analysis (p < .001). These findings demonstrate that, while CRT can achieve high T cell densities in PDAC compared to melanoma, phenotype and spatial organization of T cells may limit benefit of T cell infiltration in this immunotherapy-resistant tumor.

Impact of Treatment Parameters on Racial Survival Differences in Oropharyngeal Cancer: National Cancer Database Study.

OBJECTIVE: To investigate how differences in treatment parameters account for survival differences between races of patients with oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database. METHODS: Data of patients with OPSCC undergoing radiation therapy (RT) or concurrent chemoradiation therapy as primary treatment were obtained from the National Cancer Database from 2004 to 2016. We analyzed 4 treatment-related time intervals to determine their impact on survival between races when controlling for human papilloma virus (HPV) status. Cox proportional hazards models, stepwise logistic regressions, covariate adjustments, and propensity score matching were performed. RESULTS: A total of 3152 patients were identified (2877 White, 275 Black). In HPV- cases, Black patients with prolonged radiation duration had a significantly worse overall survival as compared with White patients (hazard ratio, 1.77; 95% CI, 1.03-3.05; P = .039). In a logistic regression model, the only covariate that was significantly associated with prolonged RT was facility type. When further adjusted for facility type, the survival difference between Black and White patients with HPV- status and prolonged RT times was no longer significant (hazard ratio, 1.55; 95% CI, 0.90-2.69; P = .116). CONCLUSIONS: There is a significant disparity in overall survival between Black and White patients with HPV- OPSCC when RT duration is prolonged. Clinicians should be aware of the negative impact of prolonged RT, especially in Black patients, so that they can attempt to decrease treatment-related time intervals. Facility type was also found to affect the outcomes of patients with OPSCC, and efforts should be made to improve patient access to well-equipped, high-volume facilities.

Two-Stage Approaches to Accounting for Patient Heterogeneity in Machine Learning Risk Prediction Models in Oncology.

PURPOSE: Machine learning models developed from electronic health records data have been increasingly used to predict risk of mortality for general oncology patients. But these models may have suboptimal performance because of patient heterogeneity. The objective of this work is to develop a new modeling approach to predicting short-term mortality that accounts for heterogeneity across multiple subgroups in the presence of a large number of electronic health record predictors. METHODS: We proposed a two-stage approach to addressing heterogeneity among oncology patients of different cancer types for predicting their risk of mortality. Structured data were extracted from the University of Pennsylvania Health System for 20,723 patients of 11 cancer types, where 1,340 (6.5%) patients were deceased. We first modeled the overall risk for all patients without differentiating cancer types, as is done in the current practice. We then developed cancer type-specific models using the overall risk score as a predictor along with preselected type-specific predictors. The overall and type-specific models were compared with respect to discrimination using the area under the precision-recall curve (AUPRC) and calibration using the calibration slope. We also proposed metrics that characterize the degree of risk heterogeneity by comparing risk predictors in the overall and type-specific models. RESULTS: The two-stage modeling resulted in improved calibration and discrimination across all 11 cancer types. The improvement in AUPRC was significant for hematologic malignancies including leukemia, lymphoma, and myeloma. For instance, the AUPRC increased from 0.358 to 0.519 (∆ = 0.161; 95% CI, 0.102 to 0.224) and from 0.299 to 0.354 (∆ = 0.055; 95% CI, 0.009 to 0.107) for leukemia and lymphoma, respectively. For all 11 cancer types, the two-stage approach generated well-calibrated risks. A high degree of heterogeneity between type-specific and overall risk predictors was observed for most cancer types. CONCLUSION: Our two-stage modeling approach that accounts for cancer type-specific risk heterogeneity has improved calibration and discrimination than a model agnostic to cancer types.

Affordable Care Act State-Specific Medicaid Expansion: Impact on Health Insurance Coverage and Breast Cancer Screening Rate.

BACKGROUND: Under the Affordable Care Act, states were given the option to expand Medicaid in 2014. By the end of 2014, 32 states had opted to expand Medicaid and 19 did not. Previous quasi-experimental studies took advantage of this state-specific policy implementation and found increased insurance coverage in expansion compared with nonexpansion states. With longer-term data now available, we studied the effect of Medicaid expansion on changes in insurance coverage and mammography rates in expansion and nonexpansion states. STUDY DESIGN: Seven states that expanded Medicaid eligibility in 2014 and 6 nonexpansion states were selected based on available data. The US Census American Community Survey was queried for insurance coverage from 2011 to 2016 and the CDC Behavioral Risk Factor Surveillance System from 2010 to 2018. Difference-in-difference linear mixed models were used to estimate and compare insurance coverage and screening mammogram rates between expansion and nonexpansion states before and after 2014. RESULTS: The increase in insurance rates for all persons covered by some type of health insurance after Medicaid expansion was significantly different in expansion than nonexpansion states (p = 0.001). The increase in Medicaid coverage was significant in expansion compared with nonexpansion states (p < 0.001). A similar trend was seen in screening mammogram rates in women from low-income households in expansion vs nonexpansion states (p = 0.049). CONCLUSIONS: Medicaid expansion states saw greater improvement in total insurance and Medicaid coverage, and in mammogram rates in lower-income women compared with nonexpansion states after Medicaid legislation was passed. Our study demonstrates that people do take advantage of expanded eligibility by acquiring insurance and this can improve access to preventive measures, such as screening mammography.

Affordable Care Act State-Specific Medicaid Expansion: Impact on Health Insurance Coverage and Breast Cancer Screening Rates.

BACKGROUND: Under the Affordable Care Act, states were given the option to expand Medicaid in 2014. By the end of 2014, 32 states had opted to expand Medicaid while 19 did not. Previous quasi-experimental studies took advantage of this state-specific policy implementation and found increased insurance coverage in expansion compared to non-expansion states. With longer-term data now available, we studied the effect of Medicaid expansion on changes in insurance coverage and mammography rates in expansion and non-expansion states. STUDY DESIGN: Seven states which expanded Medicaid eligibility in 2014 and six non-expansion states were selected based on available data. The U.S. Census American Community Survey was queried for insurance coverage from 2011-2016 and the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System from 2010-2018. Difference-in-difference linear mixed models were used to estimate and compare insurance coverage and screening mammogram rates between expansion and non-expansion states before and after 2014. RESULTS: The increase in insurance rates for all persons covered by some type of health insurance after Medicaid expansion was significantly different in expansion than non-expansion states (p=0.001). The increase in Medicaid coverage was significant in expansion compared to non-expansion states (p<0.001). A similar trend was seen in screening mammogram rates in women from low income households in expansion versus non-expansion states (p=0.049). CONCLUSION: Medicaid expansion states saw greater improvement in total insurance and Medicaid coverage, and in mammogram rates in lower income women, when compared to non-expansion states after Medicaid legislation was passed. Our study demonstrates that people do take advantage of expanded eligibility by acquiring insurance and this may improve access to preventive measures such as screening mammography.

HPV status in patients with nasopharyngeal carcinoma in the United States: A SEER database study.

PURPOSE: To investigate the etiologic and prognostic role of Human Papilloma Virus (HPV) in Nasopharyngeal Carcinoma (NPC). MATERIALS AND METHODS: Patients diagnosed with NPC were identified with the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was used to investigate the effect of clinicopathologic predictors on HPV positivity in NPC. Survival analyses were performed with Kaplan-Meier curves and Cox regression models. RESULTS: 180/517 patients (34.8%) with known HPV testing were positive for HPV-associated NPC. East Asians and individuals over 25 were less likely to have HPV-associated NPC, while controlling for AJCC-7 stage and AJCC-7 M stage. According to the survival analysis, cause-specific survival (CSS) did not differ significantly by HPV status throughout the study period, but did differ significantly by HPV ethnicity group. CONCLUSIONS: The clinical implications of HPV in NPC are further elucidated but require more investigation. LEVEL OF EVIDENCE: IV.

Establishment and maintenance of human embryonic stem cells on STO, a permanently growing cell line.

Human embryonic stem (hES) cells have been traditionally cultured on primary mouse embryonic fibroblasts (PMEFs). However, though STO cells have some advantages over PMEFs and human embryonic fibroblasts (hEFs) as feeder cells, they have never been used as feeder cells to establish hES cell lines. In this study, three hES cell lines (Miz-hES1, Miz-hES2, and Miz-hES3) were established from inner cell masses (ICM), using STO as feeder cells. The three hES cell lines had normal karyotypes and expressed high levels of alkaline phosphatase (AP), cell surface markers (SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81), and transcription factor Oct-4. After culture on STO cells for 2 yr, hES cells maintained the potential to form derivatives of all three embryonic germ layers. Our results show that STO feeder cells have the potential to support the establishment and maintenance of hES cell lines. In addition, our results suggest that laminin may play an important role in maintaining the undifferentiated proliferation of hES cells.