Temporal Geospatial Analysis of COVID-19 Pre-infection Determinants of Risk in South Carolina

Disparities and their geospatial patterns exist in morbidity and mortality of COVID-19 patients. When it comes to the infection rate, there is a dearth of research with respect to the disparity structure, its geospatial characteristics, and the pre-infection determinants of risk (PIDRs). This work aimed to assess the temporal–geospatial associations between PIDRs and COVID-19 infection at the county level in South Carolina. We used the spatial error model (SEM), spatial lag model (SLM), and conditional autoregressive model (CAR) as global models and the geographically weighted regression model (GWR) as a local model. The data were retrieved from multiple sources including USAFacts, U.S. Census Bureau, and the Population Estimates Program. The percentage of males and the unemployed population were positively associated with geodistributions of COVID-19 infection (p values \u3c 0.05) in global models throughout the time. The percentage of the white population and the obesity rate showed divergent spatial correlations at different times of the pandemic. GWR models fit better than global models, suggesting nonstationary correlations between a region and its neighbors. Characterized by temporal–geospatial patterns, disparities in COVID-19 infection rate and their PIDRs are different from the mortality and morbidity of COVID-19 patients. Our findings suggest the importance of prioritizing different populations and developing tailored interventions at different times of the pandemic

Temporal Events Detector for Pregnancy Care (TED-PC): A Rule-based Algorithm to Infer Gestational Age and Delivery Date from Electronic Health Records of Pregnant Women with and without COVID-19

Objective: To develop a rule-based algorithm that detects temporal information of clinical events during pregnancy for women with COVID-19 by inferring gestational weeks and delivery dates from Electronic Health Records (EHR) from the National COVID Cohort Collaborate (N3C). Materials and Methods: The EHR are normalized by the Observational Medical Outcomes Partnership (OMOP) Clinical Data Model (CDM). EHR phenotyping resulted in 270,897 pregnant women (2018-06-01 to 2021-05-31). We developed a rule-based algorithm and performed a multi-level evaluation to test content validity and clinical validity of the algorithm; and extreme value analysis for individuals with 300 days of gestation. Results: The algorithm identified 296,194 pregnancies (16,659 COVID-19 174 and 744 without COVID-19 peri-pandemic) in 270,897 pregnant women. For inferring gestational age, 95% cases (n=40) have moderate-high accuracy (Cohen Kappa = 0.62); 100% cases (n=40) have moderate-high granularity of temporal information (Cohen Kappa = 1). For inferring delivery dates, the accuracy is 100% (Cohen Kappa = 1). Accuracy of gestational age detection for extreme length of gestation is 93.3% (Cohen Kappa = 1). Mothers with COVID-19 showed higher prevalence in obesity (35.1% vs. 29.5%), diabetes (17.8% vs. 17.0%), chronic obstructive pulmonary disease (COPD) (0.2% vs. 0.1%), respiratory distress syndrome (ARDS) (1.8% vs. 0.2%). Discussion: We explored the characteristics of pregnant women by different timing of COVID-19 with our algorithm: the first to infer temporal information from complete antenatal care and detect the timing of SARS-CoV-2 infection for pregnant women using N3C. Conclusion: The algorithm shows excellent validity in inferring gestational age and delivery dates, which supports national EHR cohorts on N3C studying the impact of COVID-19 on pregnancy

Yttrium-90 Radioembolization and Tumor Hypoxia: Gas-challenge BOLD Imaging in the VX2 Rabbit Model of Hepatocellular Carcinoma.

Rationale and objectivesTo use a rapid gas-challenge blood oxygen-level dependent magnetic resonance imaging exam to evaluate changes in tumor hypoxia after 90Y radioembolization (Y90) in the VX2 rabbit model.Materials and methodsWhite New Zealand rabbits (n = 11) provided a Y90 group (n = 6 rabbits) and untreated control group (n = 5 rabbits). R2* maps were generated with gas-challenges (O2/room air) at baseline, 1 week, and 2 weeks post-Y90. Laboratory toxicity was evaluated at baseline, 24 hours, 72 hours, 1 hours, and 2 weeks. Histology was used to evaluate tumor necrosis on hematoxylin and eosin and immunofluorescence imaging was used to assess microvessel density (CD31) and proliferative index (Ki67).ResultsAt baseline, median tumor volumes and time to imaging were similar between groups (p = 1.000 and p = 0.4512, respectively). The median administered dose was 50.4 Gy (95% confidence interval:44.8-55.9). At week 2, mean tumor volumes were 5769.8 versus 643.7 mm3 for control versus Y90 rabbits, respectively (p = 0.0246). At two weeks, ΔR2* increased for control tumors to 12.37 ± 12.36sec-1 and decreased to 4.48 ± 9.00sec-1 after Y90. The Pearson correlation coefficient for ΔR2* at baseline and percent increase in tumor size by two weeks was 0.798 for the Y90 group (p = 0.002). There was no difference in mean microvessel density for control versus Y90 treated tumors (p = 0.6682). The mean proliferative index was reduced in Y90 treated tumors at 30.5% versus 47.5% for controls (p = 0.0071).ConclusionThe baseline ΔR2* of tumors prior to Y90 may be a predictive imaging biomarker of tumor response and treatment of these tumors with Y90 may influence tumor oxygenation over time

Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model.

PurposeTo evaluate the combination of 90Y radioembolization (Y90) and drug-eluting bead irinotecan (DEBIRI) microspheres in the VX2 rabbit model.Materials and methodsAn initial dose finding study was performed in 6 White New Zealand rabbits to identify a therapeutic but subcurative dose of Y90. In total, 29 rabbits were used in four groups: Y90 treatment (n = 8), DEBIRI treatment (n = 6), Y90 + DEBIRI treatment (n = 7), and an untreated control group (n = 8). Hepatic toxicity was evaluated at baseline, 24 h, 72 h, 1 week, and 2 weeks. MRI tumor volume (TV) and enhancing tumor volume were assessed baseline and 2 weeks. Tumor area and necrosis were evaluated on H&E for pathology.ResultsInfused activities of 84.0-94.4 MBq (corresponding to 55.1-72.7 Gy) were selected based on the initial dose finding study. Infusion of DEBIRI after Y90 was technically feasible in all cases (7/7). Overall, 21/29 animals survived to 2 weeks, and the remaining animals had extrahepatic disease on necropsy. Liver transaminases were elevated with Y90, DEBIRI, and Y90 + DEBIRI compared to control at 24 h, 72 h, and 1 week post-treatment and returned to baseline by 2 weeks. By TV, Y90 + DEBIRI was the only treatment to show statistically significant reduction at 2 weeks compared to the control group (p = 0.012). The change in tumor volume (week 2-baseline) for both Y90 + DEBIRI versus control (p = 0.002) and Y90 versus control (p = 0.014) was significantly decreased. There were no statistically significant differences among groups on pathology.ConclusionIntra-arterial Y90 + DEBIRI was safe and demonstrated enhanced antitumor activity in rabbit VX2 tumors. This combined approach warrants further investigation

18F-FDG PET Biomarkers Help Detect Early Metabolic Response to Irreversible Electroporation and Predict Therapeutic Outcomes in a Rat Liver Tumor Model.

Purpose To test the hypothesis that biomarkers of fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-μsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUVmax) was calculated 3 days after IRE. The maximum lesion diameter change (ΔDmax) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUVmax and ΔDmax were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUVmax at 3 days and ΔDmax (or apoptosis index) at 14 days after IRE treatment. Results ΔSUVmax, ΔDmax, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUVmax 3 days after IRE and ΔDmax 14 days after IRE (R = 0.66, P = .01) and between ΔSUVmax 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion 18F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model. © RSNA, 2017