Minnesota Research Articles

A practical framework for applied forestry assisted migration

Recent and projected changes in climate over this century pose an unprecedented threat to the health, diversity, and productivity of forest ecosystems. Forests have migrated and adapted to long-term changes in climate over thousands to millions of years; however, natural migration rates and adaptive responses of tree populations cannot match the rapid pace of current climate change. Consequently, more climate-informed approaches to reforestation are needed as current reforestation strategies using local seed sources may no longer be adequate to meet forest management objectives. Assisted migration is a climate change adaptation technique that can help maintain the ecosystem services and economic value that forests provide. Forestry assisted migration (FAM) focusses on the movement of populations of widespread, commercially, or ecologically important forest tree species within or just beyond their current ranges as a way to maintain forest productivity and health in the face of climate change. Although the forestry community recognizes FAM as a reforestation tool, guidance for planning and implementation of FAM is lacking and a framework that provides this guidance can prove useful to land managers with limited time and resources available who want to undertake FAM. We developed a practical framework (the FAM Framework) to provide a structured approach to ensure the most important considerations and best available science are utilized by land managers wanting to implement FAM on their land base. The FAM Framework incorporates multiple factors for the application of FAM in four sequential phases: assessment and analysis, climate-based plant material selection, seed procurement and deployment, and documentation and monitoring. The FAM Framework was tested by developing an assisted migration plan for the Superior National Forest, Minnesota (MN), and lessons learned from the development of this specific plan were used to revise and improve the FAM Framework for suitability across all lands. While originally designed to meet the needs of National Forest System land managers, it is relevant and applicable across the spectrum of land ownership because it incorporates consideration of critical elements in planning and implementing FAM on any landscape while facilitating adaptive management for active learning and future implementation.

Mortality risk in patients with carotid artery disease undergoing carotid endarterectomy compared to the general population

Abstract Background Patients with carotid artery disease undergoing carotid endarterectomy (CEA) appear to be at high risk of all-cause mortality during their follow-up. However, the possible predictors of this adverse outcome are not elucidated yet. Purpose We aimed to test cardiovascular (CV) risk factors as possible predictors of all-cause mortality in patients undergoing CEA and to determine whether there is a difference between the mortality rate of our study cohort and the general population. We hypothesize that CEA-treated patients have a higher mortality rate during follow-up after surgery than the general population, which is not related to the presence of CV risk factors. Methods We prospectively enrolled and followed up patients undergoing CEA. Univariate and multivariable Cox regression were performed to test whether common CV risk factors (demographics, laboratory values, comorbidities, and events before CEA) were predictive of all-cause mortality. We then compared the standardized mortality ratio (SMR) of our population and the age-sex-matched Minnesota (MN) general population at 5,10, and 21 years of follow-up after CEA. Results A total of 710 patients were followed for a median of 7.1 [2.9-11.9] years after CEA. Mortality occurred in 198 (27.0%) patients during the follow-up. The median time to event was 11.0 [10.0-12.0] years. Age was the only predictor of all-cause mortality in CEA-treated patients in multivariable models adjusted for known CV risk factors (Model 1: HR 1.03 [95%CI 1.01-1.06]; p=0.004; Model 2: HR 1.02 [95%CI 1.00-1.04]; p=0.023) (Table 1). However, the CEA-treated group had a higher mortality rate than would have been expected in the MN population (log-rank p<0.001) (Fig.1A). Compared to the MN population, at 5 years of follow-up only patients <60 years old had a higher SMR (4.53 [1.95-8.92]; p=0.001), whereas, at 10 years and 21 years of follow-up, our study population had a higher mortality rate at any age (Fig.1B). Conclusions The elevated mortality risk post-CEA in our cohort cannot be solely attributed to chronological aging. The underlying process of atherosclerosis likely contributes to all-cause mortality, and plaque characteristics may offer additional insight into the risk stratification of this patient group.All cause mortality predictors after CEAStudy population vs. MN population SMR

Emergency department visits and hospitalizations attributable to recent Epstein-Barr virus infection

Objective Infectious mononucleosis (IM) or mono is typically caused by primary infection with Epstein-Barr virus (EBV) and may have a months-long, complicated course. We utilized population-based data to add to the limited literature on health care utilization following EBV infection. Methods The Rochester Epidemiology Project includes medical records for ∼60% of residents living in 27 counties of Minnesota (MN) and Wisconsin (WI). Persons meeting a case definition of recent EBV infection from 1 January 1998 to 31 December 2021 were compared to three persons not meeting the definition, matched on case’s sex, age, and index date. Emergency department (ED) visits and hospitalizations in the two groups were compared during 5-years’ follow-up divided into three periods (short-term ≤3 months, mid-term >3 months–1 year, long-term >1–5 years). Adjusted hazard ratios (AHR) were estimated to account for the potential influence of confounding variables. Results In total, 6,423 persons had a recent EBV infection and were matched to 19,269 comparators. The risk of an ED visit was significantly higher among cases in the short-term period (24.3% vs referents: 7.6%, p <.001; AHR = 3.71, 95% CI = 3.41–4.03). Cases also had an increased risk of hospitalization in the short-term (5.2% vs 1.6%: referents, p <.001; AHR = 3.53, 95% CI = 2.94–4.24). For ED visits but not hospitalization, the excess risk persisted into the mid-term follow-up period. Persons without a concurrent clinical diagnosis of IM continued to have an increased risk of hospitalizations up to 1 year after index date (AHR = 1.45, 95% CI = 1.09–1.91) and an increased risk of ED visits up to 5 years after the index date (AHR = 1.29, 95% CI = 1.14–1.46). Conclusion There is a substantial short- and mid-term increased risk of serious health care encounters associated with recent EBV infection. Mid- and long-term risks are increased in patients who do not have a concomitant diagnosis of IM.

Telehealth adoption for substance use and mental health disorders in Minnesota and North Dakota: a quasi-experimental study.

The coronavirus disease 2019 (COVID-19) pandemic necessitated rapid adoption of telehealth services to maintain healthcare access for treating substance use disorders (SUDs) and mental health care (MHC). However, the impacts of telehealth expansion policies adopted in 2020 on access to addiction treatment in North Dakota (ND) and Minnesota (MN) remain unclear. This study examines the impact of the COVID-19 pandemic on utilization of telehealth services for SUDs and MHC in ND and MN. We conducted a quasi-experimental study design using Medicaid telehealth claims data from 2018 to 2022. Segmented regression analysis of interrupted time series (ITS) data was employed to assess the impact of the COVID-19 pandemic (March 2020) on telehealth service utilization. From 2018 to 2022, there were 580,186 telehealth claims for SUDs (MN: 545,676; ND: 34,510) and 3.4 million claims for MHC (MN: 3.3 million; ND: 85,391). The mean telehealth utilization rate for SUDs was 5.2 vs. 7.3 per 1,000 beneficiaries and for MHC was 12.6 vs. 45.2 per 1,000 beneficiaries in ND and MN, respectively. The pandemic led to significant increases in telehealth use: ND (SUDs: +22.7/1,000; MHC: +59.8/1,000) and MN (SUDs: +30/1,000; MHC: +185.5/1,000). ND saw smaller initial increases but more gradual declines over time (SUDs: -0.42/1,000/month; MHC: -1.03/1,000/month) compared to MN (SUDs: -0.43/1,000/month; MHC: -2.78/1,000/month). The COVID-19 pandemic significantly increased Medicaid telehealth utilization for SUDs and MHC in both states. MN experienced larger initial increases with steeper declines, while ND showed more sustainable utilization trends, indicating potential for sustained improvements in access to behavioral health services.

Epigenetic Aging and Racialized, Economic, and Environmental Injustice

Epigenetic age acceleration is associated with exposure to social and economic adversity and may increase the risk of premature morbidity and mortality. However, no studies have included measures of structural racism, and few have compared estimates within or across the first and second generation of epigenetic clocks. To determine whether epigenetic age acceleration is positively associated with exposures to diverse measures of racialized, economic, and environmental injustice measured at different levels and time periods. This cross-sectional study used data from the My Body My Story (MBMS) study between August 8, 2008, and December 31, 2010, and examination 5 of the Multi-Ethnic Atherosclerosis Study (MESA) from April 1, 2010, to February 29, 2012. In the MBMS, DNA extraction was performed in 2021; linkage of structural measures to the MBMS and MESA, in 2022. US-born individuals were randomly selected from 4 community health centers in Boston, Massachusetts (MBMS), and 4 field sites in Baltimore, Maryland; Forsyth County, North Carolina; New York City, New York; and St Paul, Minnesota (MESA). Data were analyzed from November 13, 2021, to August 31, 2023. Ten epigenetic clocks (6 first-generation and 4 second-generation), computed using DNA methylation data (DNAm) from blood spots (MBMS) and purified monocytes (MESA). The US-born study population included 293 MBMS participants (109 men [37.2%], 184 women [62.8%]; mean [SD] age, 49.0 [8.0] years) with 224 Black non-Hispanic and 69 White non-Hispanic participants and 975 MESA participants (492 men [50.5%], 483 women [49.5%]; mean [SD] age, 70.0 [9.3] years) with 229 Black non-Hispanic, 191 Hispanic, and 555 White non-Hispanic participants. Of these, 140 (11.0%) exhibited accelerated aging for all 5 clocks whose estimates are interpretable on the age (years) scale. Among Black non-Hispanic MBMS participants, epigenetic age acceleration was associated with being born in a Jim Crow state by 0.14 (95% CI, 0.003-0.27) SDs and with birth state conservatism by 0.06 (95% CI, 0.01-0.12) SDs, pooling across all clocks. Low parental educational level was associated with epigenetic age acceleration, pooling across all clocks, for both Black non-Hispanic (0.24 [95% CI, 0.08-0.39] SDs) and White non-Hispanic (0.27 [95% CI, 0.03-0.51] SDs) MBMS participants. Adult impoverishment was positively associated with the pooled second-generation clocks among the MESA participants (Black non-Hispanic, 0.06 [95% CI, 0.01-0.12] SDs; Hispanic, 0.07 [95% CI, 0.01-0.14] SDs; White non-Hispanic, 0.05 [95% CI, 0.01-0.08] SDs). The findings of this cross-sectional study of MBMS and MESA participants suggest that epigenetic age acceleration was associated with racialized and economic injustice, potentially contributing to well-documented inequities in premature mortality. Future research should test the hypothesis that epigenetic accelerated aging may be one of the biological mechanisms underlying the well-documented elevated risk of premature morbidity and mortality among social groups subjected to racialized and economic injustice.

Abstract 3469: Exploring the impact of a giant inflatable colon on the level of awareness, knowledge, and intent for colorectal cancer screening among men attending two state fairs in the Midwest

Abstract Purpose: This study aimed to evaluate the influence of an interactive inflatable colon as an effective educational tool to increase colorectal cancer (CRC) awareness, knowledge, and screening intention among men attending the Wisconsin (WI) and Minnesota (MN) state fairs. Methods: Eligible study participants were self-identified men aged 18-75 who spoke English, were residents of WI or MN, and able to read in English. The study was employed during the final operating weekend of both the 2023 WI State Fair (August 11-13) and the MN State Fair (September 1-3). Eligible participants completed: (1) a pre-survey, (2) an unguided tour of the inflatable “Super Colon”, and then (3) a post-survey. The primary outcomes of interest were change in awareness (two items), knowledge (four items), and behavioral intent to obtain CRC screening (one item) from pre- to post-survey. Chi-square tests were used to examine study site differences and to explore the association between demographics and behaviors (awareness, knowledge, intentions) before entry to the Super Colon. McNemar’s test were employed to test if there were significant differences in the distributions from pre- to post-survey. Results: A total of 940 eligible participants were included in the study sample. The men self-identified their race/ethnicity as Non-Hispanic (NH) White (72%), followed by NH other (12%), NH Black (9%), and Hispanic (8%). Race and ethnicity significantly varied by study site (&amp;lt;.0001) with participants from WI more likely being members of racial/ethnic groups that are often medically underserved (33% vs. 24% in MN). Only 13% of participants had walked through an inflatable colon before. Of those who were screening-age appropriate (age 45 or older), 89% had been screened for CRC previously. With the exception of one question, baseline CRC knowledge was relatively high among our study sample. Interestingly, having higher confidence of their awareness level was inversely associated with higher knowledge. As a result of touring the Super Colon, a significant improvement in confidence in individuals’ knowledge of CRC (&amp;lt;.0001), knowledge regarding a colon polyp (&amp;lt;.0001), and intentions to be screened in the future (&amp;lt;.0001) were observed. Most participants (95%) agreed that the Super Colon is an effective educational tool to teach people about CRC. Conclusion: Since both encouraging CRC screening uptake and increasing research study participation among men can be a difficult task, these findings emphasize the crucial role of community-based educational initiatives in achieving these goals. Our findings affirm how the three-dimensional interior of the Super Colon is as an effective educational tool for promoting CRC early detection screening behaviors among men and increasing their awareness. Citation Format: Ami E. Sedani, Kelly K. Rifelj, Malcolm S. Bevel, Cordero L. McCall, Mckenzi Rogalla, Lisa Laliberte, Kiara Ellis, Rebekah J. Pratt, Charles R. Rogers. Exploring the impact of a giant inflatable colon on the level of awareness, knowledge, and intent for colorectal cancer screening among men attending two state fairs in the Midwest [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3469.

Abstract TMP20: Mapping the Expansion of the Minnesota Stroke System of Care

Objectives: Stroke is the fifth leading cause of death in Minnesota (MN) and in the United States. The state of MN a has a unique geographical layout with many healthcare facilities located in rural areas. In 2013 legislation was passed authorizing the Minnesota Department of Health to designate hospitals as Acute Stroke Ready Hospitals, Primary Stroke Centers, and Comprehensive Stroke Centers. When a hospital joins the MN Stroke System they maintain vital infrastructure, expertise, and care processes to provide high quality stroke care in accordance with evidence-based guidelines. We used geographic information systems (GIS) methods to visualize the growth and expansion of the Minnesota Stroke System and quantify its reach to Minnesotans across the state over a 10-year period. Methods: Using the Network Analyst extension of ESRI ArcGIS Desktop 10.8.2, 30- and 60- minute drive time service areas were calculated around each designated hospital in 2013, 2017 and 2023. Census block groups were identified where the mean center of population fell within the 30-minute drive time areas and the populations of those block groups were summed. A percentage was calculated using the total Minnesota population as the denominator. Results: In 2013, only 66% of Minnesota’s population lived within 30 minutes of a designated stroke center and 80% lived within a 60-minute drive time. Stroke designated hospitals (19) were largely concentrated in metropolitan areas, leaving many rural Minnesotans without ready access to stroke centers. After the first cycle in 2017, or three-year period post statute, drive time status increased to 90% of the population living within 30 minutes of a designated stroke system hospital and 98% living within a 60- minute drive time. As of 2023, 94% of Minnesotans now live within a 30-minute drive of a designated Stroke System Hospital and 99% live within a 60-minute drive time. Conclusions: Stroke statute was the catalyst for improving stroke care access in MN. The voluntary system of care expanded rapidly from 19 initial hospitals to 119 over a 10-year period. This progress means more than 1.9 million additional Minnesotans now have better access to emergency stroke care.

Metataxonomic Analysis of Microbial Communities in Aquaponic Systems at Two Facilities in the Midwest United States

Aquaponic production relies on microbial activity to convert fish wastes into nutrients for plants. An aquaponic system contains multiple compartments that each have varying environmental pressures that can impact the types of microbes living in the compartment. Furthermore, differences in fish and plant species, system startup and management, and water source can impact microbial communities that colonize an aquaponic system. In this study, we sampled two aquaponic facilities that each operated six replicate aquaponic systems. Metataxonomic analyses were performed on the samples to compare the microbial communities of aquaponic facilities in Minnesota (MN) and Wisconsin (WI), assess the consistency of the microbial communities across multiple systems within a single facility, and evaluate the abundance and types of microbes present within each compartment of a system. Proteobacteria, Bacteroidetes, and Actinobacteria were common in both facilities, but nitrifying organisms were in greater abundance at the WI facility. Microbial communities were largely consistent among systems within a facility, but microbial communities among different compartments of the systems varied. Nitrifying organisms were primarily associated with the biofilter compartment of the MN systems but were found throughout the WI systems, which do not have a dedicated biofiltration compartment. While nitrifying organisms have an important role in an aquaponic system, they comprise less than 10% of the total microbial community of the aquaponic systems we sampled. Other taxa are likely to have equally important roles in the productivity of an aquaponic system, but those taxa and their functions have not been well characterized, and it is unclear how system startup, management, and other factors impact colonization and maintenance of these taxa.

Risk of hospitalization in synucleinopathies and impact of psychosis.

Few studies have investigated the risk of hospitalization among patients with synucleinopathies (Parkinson disease, Dementia with Lewy Bodies, Parkinson disease dementia, Multiple System Atrophy) with associated psychosis and the impact of antipsychotic treatments on hospital admissions and duration of the stay. To determine the risk of hospitalization among patients with synucleinopathies and in patients with associated psychosis. To evaluate the impact of antipsychotic treatments on hospital admission of patients with synucleinopathies and psychosis in an incident cohort study in Olmsted County, Minnesota (MN). We used the Rochester Epidemiology Project (REP) to define an incident cohort of patients with clinically diagnosed synucleinopathies (1991-2010) in Olmsted County, MN. A movement disorder specialist reviewed all medical records to confirm the clinical diagnosis of synucleinopathies using the NINDS/NIMH unified diagnostic criteria. We included 416 incident cases of clinically diagnosed synucleinopathies from 2,669 hospitalizations. 409 patients (98.3%) were admitted to the hospital at least once for any cause after the onset of parkinsonism. The median number of hospitalizations for a single patient was 5. In total, 195 (46.9%) patients met the criteria for psychosis: patients with psychosis had a 49% (HR = 1.49, p < 0.01) increased risk of hospitalization compared to patients without psychosis. Among patients with psychosis, 76 (39%) received antipsychotic medication. Treatment with antipsychotic medications did not affect the risk of hospitalization (HR = 0.93, p = 0.65). The median length of hospitalization among the entire cohort was 1 (IQR 0-4) day. There was no difference between hospitalization length for patients with no psychosis and patients with active psychosis (RR = 1.08, p = 0.43) or patients with resolved psychosis (RR = 0.79, p = 0.24). Psychosis increases the risk of hospitalization in patients with clinically defined synucleinopathies; however, it does not affect the length of hospital stays in our cohort. Antipsychotic treatment does not affect the risk of hospitalization in our study.

Herd-level risk factors associated with chronic wasting disease-positive herd status in Minnesota, Pennsylvania, and Wisconsin cervid herds.

The objective of this study was to evaluate risks related to introduction of Chronic Wasting Disease (CWD) to farmed cervid herds in Minnesota (MN), Pennsylvania (PA), and Wisconsin (WI). This was the first study to evaluate risk factors related to multiple pathways of CWD transmission to farmed cervid herds. Participating herds in this case-control study included 22 case and 49 control herds identified through participation in the respective mandatory State CWD herd program. Data was voluntarily collected from white-tailed deer (WTD) study herds using a questionnaire and state animal health agency databases. Univariable analyses identified associations between CWD-positive herds and variables representing different transmission pathways, including direct contact with infected farmed cervids (imported from a herd that later tested positive for CWD) odds ratio (OR):7.16, 95 % confidence intervals (CI):1.64-31.21 and indirect contact with infected wild cervids (access of domestic cats to pens or feed storage area) OR:4.07, 95 % CI:1.35-12.26, observed evidence of mammalian scavengers inside or outside of fenceline in the previous 12 months OR:6.55, 95 % CI:1.37-31.32, ≤5km distance to nearest detected CWD-positive wild cervid OR:3.08, 95 % CI:1.01-9.39, forested area crosses the perimeter fenceline OR:3.54, 95 % CI:1.13-11.11, ≤0.3m distance of water source to fenceline OR:4.71, 95 % CI:1.60-13.83, and water source shared with wild cervids (running or standing water) OR:4.17, 95 % CI:1.34-12.92. Three variables from univariable analyses that represented different biological transmission pathways were placed in a Firth's penalized maximum likelihood multivariable logistic regression to evaluate associations between transmission pathway and CWD herd infection status. For the issue of low sample size and overfitting, 95 % CIs for estimated coefficients for the three variables were computed via bootstrapping of 10,000 independent bootstrap samples. The three biological variables were significantly associated with herd CWD infection status: imported cervids from a herd that later tested positive for CWD (OR:5.63; 95 % CI:1.1-28.2), ≤0.3m distance of cervid water source to perimeter fenceline (OR:4.83; 95 % CI:1.5-16.1), and ≤5km distance to nearest detected CWD-positive wild cervid (OR:4.10; 95 % CI:1.1-15.2). The risk factors associated with CWD herd status identified in this study indicated the importance of transmission through direct contact pathways with infected cervid herds (introduction of cervids from herds later identified as CWD-infected) and indirect contact pathways with infected wild cervids that could be related to other animals through the perimeter fence. Further studies are needed to confirm and clarify understanding of indirect pathways to allow development of improved biosecurity practices to prevent CWD introduction to cervid herds.

First Report of Leaf Spot of Sugar Beet Caused by Stemphylium vesicarium in Minnesota, USA.

In July 2021, sugar beet (Beta vulgaris L.) leaves with numerous tan to brown spots with white-bleached center and oval to irregularly shaped were collected from a field in Minnesota (MN) (46.2774° N, 96.3100° W), with 15% disease incidence and 30% disease severity. Leaves were washed with tap water then surface disinfected in 1% NaOCl aqueous solution for 1 min. Samples were rinsed thrice with sterile distilled water and dried in a laminar flow hood. A 2-cm leaf disc was plated on potato dextrose agar amended with streptomycin sulfate (200 mg/L) and incubated for four days at 25°C under 12-h light/dark cycle. Single spore cultures were obtained by suspending in sterile water spores harvested from a single colony. The suspension was streaked on a dish with V8 agar media and incubated as described. Five pure cultures were transferred to clarified V8 agar media for morphological feature observations. Colonies were uniform in appearance and developed light to olivaceous green mycelium. Conidia were dark brown to olivaceous green in color and measured 30 × 18 μm (n=20). They were oblong to broadly oval shaped muriform, and multiseptated (1 to 5 septa). Hyphae were septate and pale brown. Conidiophores were short, septate, and light to dark brown in color. Based on the morphological characteristics, isolates were identified as Stemphylium vesicarium (Simmons 1969). Genomic DNA of all five isolates were extracted using the DNeasy Plant Mini Kit (Qiagen, Hilden, Germany). PCR amplification and sequencing of the internal transcribed spacer (ITS) region (ITS1/ITS4 primers), the largest subunit of RNA polymerase II (5F2/7cR primers) (O'Donnell et al. 2009), the plasma membrane ATPase (ATPD-F1/ATPD-R1) gene (Lawrence et al. 2013), glyceraldehyde-3-phosphate-dehydrogenase gene (GAPDH) (gpd1/gpd2) (Berbee et al. 1999), and β-tubulin gene (Bt2a/Bt2b primers) (Glass and Donaldson 1995) were done using standard procedures. Sequences were submitted to GenBank under accession numbers OP584331 (ITS), OP589289 (RPB2), OP589290 (ATPase), OP994239 (GAPDH) and OP382477 (β-tubulin). The BLASTN search of the sequences showed 100% similarity with MT629829 (ITS) (525/525 bp), KC584471 (RPB2) (859/859 bp), JQ671770 (ATPase) (794/794 bp), MK105974 (GAPDH) (519/519 bp) and MN410922 (β-tubulin) (320/320 bp) reference sequences of S. vesicarium. Pathogenicity tests were done using four cv. Maribo MA 504 plants. S. vesicarium spore suspensions (1 × 106/ml) were sprayed on three leaves from each plant. This trial was repeated with three replicates. A similar group of plants were sprayed with autoclaved distilled water to serve as non-inoculated control. All plants were incubated in the mist chamber for 5 days at 25°C, under daily 14/10 light-dark cycles, and >80% relative humidity, then transferred to the greenhouse kept at 23 ± 2°C and a 12-h photoperiod. Fifteen days post-inoculation, all inoculated plants had multiple lesions with dark brown margins with a grayish center, and non-inoculated control plants were asymptomatic. The re-isolated fungus was morphologically similar to isolates retrieved from the field. S. vesicarium was reported on sugar beet in Michigan (Metheny et al. 2022). This is the first report of S. vesicarium causing disease on sugar beet in MN. Stemphylium sp. is a major problem of sugar beet in the Netherlands (Hanse et al. 2015). Efforts should be made to prevent introduction of susceptible beet cultivars so that the disease does not become widespread in the USA.

Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease

Treatments that aid inflammation resolution, immune tolerance, and epithelial repair may improve outcomes beyond high-dose corticosteroids and other broad immunosuppressants for life-threatening acute graft-versus-host disease (aGVHD). We studied the addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF; Pregnyl; Organon, Jersey City, NJ) to standard aGVHD therapy in a prospective Phase II clinical trial (ClinicalTrials.gov identifier NCT02525029). Twenty-two patients with Minnesota (MN) high-risk aGVHD received methylprednisolone 48 mg/m2/day plus 2000 units/m2 of uhCG/EGF s.c. every other day for 1 week. Patients requiring second-line aGVHD therapy received uhCG/EGF 2000 to 5000 units/m2 s.c. every other day for 2 weeks plus standard of care immunosuppression (physician's choice). Responding patients were eligible to receive maintenance doses twice weekly for 5 weeks. Immune cell subsets in peripheral blood were evaluated by mass cytometry and correlated with plasma amphiregulin (AREG) level and response to therapy. Most patients had stage 3-4 lower gastrointestinal tract GVHD (52%) and overall grade III-IV aGVHD (75%) at time of enrollment. The overall proportion of patients with a response at day 28 (primary endpoint) was 68% (57% with complete response, 11% with partial response). Nonresponders had higher baseline counts of KLRG1+ CD8 cells and T cell subsets expressing TIM-3. Plasma AREG levels remained persistently elevated in nonresponders and correlated with AREG expression on peripheral blood T cells and plasmablasts. The addition of uhCG/EGF to standard therapy is a feasible supportive care measure for patients with life-threatening aGVHD. As a commercially available, safe, and inexpensive drug, uhCG/EGF added to standard therapy may reduce morbidity and mortality from severe aGVHD and merits further study.

Socioeconomic impacts of COVID-19 pandemic on foodborne illnesses in the United States

Foodborne diseases continue to impact human health and the economy. The COVID-19 pandemic has dramatically affected the food system from production to consumption. This project aims to determine the impact of the COVID-19 pandemic on the spread of foodborne diseases and the factors that may have contributed, including environmental, behavioral, political, and socioeconomic. Data for this study were collected from The Foodborne Diseases Active Surveillance Network (FoodNet) for 2015-2020. FoodNet personnel located at state health departments regularly contact the clinical laboratories in Connecticut (CT), Georgia (GA), Maryland (MD), Minnesota (MN), New Mexico (NM), Oregon (OR), Tennessee (TN), and selected counties in California (CA), Colorado (CO), and New York (NY). Data were analyzed using SAS to determine the changes in rates of foodborne pathogens reported in FoodNet before and during the COVID-19 pandemic in the ten reporting states. Results of the study showed a significant decline in the incidences of foodborne diseases ranging between 25% and 60%. A geographical variation was also observed between California and states with the highest decline rate of foodborne illnesses. Policies and restrictions, in addition to environmental and behavioral changes during the COVID-19 pandemic, may have reduced rates of foodborne diseases.

A Population-Based Evaluation of Polymicrobial Staphylococcus aureus Bacteremia.

To provide an evaluation of incidence and six-month mortality rates of polymicrobial Staphylococcus aureus bacteremia (p-SAB) in the United States (US). A retrospective population-based study of all incident adults with monomicrobial SAB (m-SAB) and p-SAB in Olmsted County, Minnesota (MN) from 1 January 2006, through 31 December 2020, was conducted. Demographics, clinical characteristics, in-hospital outcomes, and six-month survival were compared between groups. Overall, 31 incident p-SAB cases occurred during the 15-year study period, corresponding to an overall age- and sex-standardized incidence rate of 1.9/100,000 person-years (95% CI, 1.3-2.6). One-third of p-SAB cases were due to MRSA, and almost one-half (15/31) were caused by Gram-positive bacteria. As compared to the 541 cases with incident m-SAB, p-SAB patients were more likely to have a catheter-related infection (p = 0.008) and less likely to be community-acquired cases (p = 0.027). The unadjusted risk of six-month mortality was greater in the p-SAB group (14/31, 45.2%) compared to the m-SAB group (144/541, 26.6%) (HR = 1.94, 95% CI = 1.12-3.36, p = 0.018). After adjusting for relevant covariates, this difference approached significance (HR = 1.93, 95% = CI 0.96-3.87, p = 0.064). To our knowledge, the current investigation represents the only US population-based study evaluating p-SAB patients. We found lower incidence rates for p-SAB than previously reported, with almost one-half of the cases caused by Gram-positive bacteria. Furthermore, these patients had poor survival compared to incident m-SAB cases.

Prevalence of cerebrovascular accidents in patients with ulcerative colitis in a single academic health system

In general, IBD increases arteriovenous thromboembolic events, though the association between UC and cerebrovascular complications remains inconclusive. Some studies suggest young women with UC have an increased risk of cerebrovascular accidents (CVA). The focus of this study was to characterize the rates, anatomic distribution, and risk factors for CVA in patients with UC. We developed a retrospective cohort of patients with UC at a single health care system from June 2010 to June 2015. Neuroimaging was used to document presence, location and type of stroke and traditional risk factors were considered. Prevalence of CVAs in patients with UC was compared to that of the general population of Minnesota (MN) and the United States (U.S.). A total of 2,183 UC patients were identified (1088 females [f-UC], 1095 males [m-UC]). The prevalence of CVA in UC patients (4.7%, 95% CI 3.9–5.6) was higher than in the U.S. (2.5–2.7%, p < 0.0001) and in Minnesota (1.8% CI 1.5–2.2, p < 0.0001) . The prevalence increased in both sexes with a peak prevalence of 24.7% (95% CI 17.1–34.4) in women with UC over the age of 80. Older age, cancer and atrial fibrillation were risk factors for CVA in univariate analysis for both sexes. In multifactorial analysis, both age and atrial fibrillation were risk factors for CVA in the m-UC cohort, but only age was associated with CVA in f-UC. The most common type of CVA was ischemic stroke (77.7%). The most common locations for CVAs in UC patients were frontal and occipital lobes (19% and 18%, respectively). UC patients have an increased risk for CVA, with women over 80 demonstrating the highest risk. Providers should be aware of these risks in making treatment decisions for UC.

Small open economies and external shocks: an application of Bayesian global vector autoregression model.

This study assesses the impact of external shocks on select small open economies (SOEs) using the Bayesian variant of the global vector autoregression model with time varying parameters and stochastic volatility. We account for the curse of dimensionality in the multi-country VAR system by implementing three different priors in the estimation of the parameters of the model: the Minnesota (M-N) prior of Doan–Litterman et al. (1984; Litterman 1986); the Normal-Gamma (N-G) prior of Park and Casella (Bayesian Anal 1:515–533, 2008); and the Stochastic Search Variable Selection (SSVS) prior of George and McCulloch (1995) as extended by Koop and Korobilis (2010, 2013). From our simulation results, we found that global economies of the USA, Western Europe and China are the major drivers of cyclical fluctuation in the SOEs. However, in spite of the perceived superior influence of China on the SOEs GDPs’ response to external shocks, we found no evidence to conclude that the influence is significantly greater than those exerted by the United States or Europe on the bloc’s economies.

Exploring a Climate Gradient of Midwestern USA Agricultural Landscape Runoff Using Deuterium (δD) and Oxygen-18 (δ18O)

Intensive agricultural activities have altered the hydrology of many Midwestern USA landscapes. Drain tiles (subsurface corrugated and perforated flexible tubing) has changed how and when water is discharged into the streams. Stable isotopes of oxygen (oxygen-18) and hydrogen (deuterium) were used to investigate hydrologic characteristics of three intensively managed agricultural landscapes in southern Minnesota (MN) and South Dakota (SD). Monthly δD and δ18O samples were collected across a climatic gradient from March 2016 to March 2018. Local meteoric water lines were established for the comparison of precipitation and evaporation magnitude from different sources at each location. These included vadose zone, phreatic zone, deep groundwater, tile drain, and river source waters. Two end-member hydrograph separation was performed at each site on selected dates to partition the shallow groundwater tile drainage contribution to streamflow. A lumped parameter modeling approach was applied to each dataset to investigate the mean transit time of water through different zones. Local meteoric water lines demonstrated differences in isotopic signatures due to the climate gradient to show the impact of low humidity and less rainfall. The hydrograph separation results showed that, from west South Dakota to eastern Minnesota, tile drains contributed about 49%, 64%, and 50% of the watershed streamflow. Precipitation took an average of 9 months to move through different pathways to end up in groundwater and an average of 4 months to end up in tile drains. This study confirms the important role tile drains play in the intensively managed fields and watersheds of Midwestern agriculture.

Application of Bayesian Space-Time interaction models for Deer-Vehicle crash hotspot identification

The objective of this research was to identify and prioritize deer-vehicle crash (DVC) hotspots using five years of crash data. This study applied Bayesian spatiotemporal models for the identification of the DVC hotspots. The Bayesian spatiotemporal model allows to observe area-specific trends in the DVC data and highlights specific locations where DVC occurrence is deteriorating or improving over time. Census Tracts (CTs) were used as the geographic units to aggregate DVC, land use, and transportation infrastructure related data of Minnesota (MN) for the year 2015 to 2019. Several tests were conducted to evaluate the performance of the hotspot identification methods. The result showed that Type-I spatiotemporal interaction model (Model-2) outperforms other four space–time models in terms of predicting DVC frequency in CTs and hotspot identification performance test measures. Results showed that forest area, vegetation, and wetland percentages were positively associated with DVC frequency, whereas the percentage of developed land use was negatively associated with DVC frequency. The findings of this study suggest that the deer population plays an important role in DVCs, which indicates that deer population management is necessary to minimize the DVC risks. Using the final Type-I spatiotemporal interaction model, 65 “High-High” CTs were identified, where both the posterior mean of the decision parameter (potential for safety improvement) and the area-specific trend were higher. The distribution of the identified hotspots showed that the risk of DVCs was more in suburban areas with mixed land use conditions. These CTs represent high-risk zones, which need immediate safety improvement measures to reduce the DVC risks. As DVC can occur at any roadway segment location, DVC hotspots information is important for safety engineers and policymakers to implement area specific countermeasures.

Lessons Learned From Focus Groups and Community Education Provision in the African American Community

The present symposium will synthesize themes derived from eight different projects designed to better understand dementia in Minnesota (MN) within the African American community (where individuals are disproportionately susceptible to dementia and the tolls of dementia care). These projects included focus groups, community outreach, community education, networking with aging service providers, and community forums. Projects were funded by and conducted in partnership with the MN Department of Human Services, the Alzheimer’s Association, the MN Board on Aging, and the MN Leadership Council on Aging’s Diverse Elders Coalition. Themes included the unique ways that African American elders share their viewpoints and the importance of faith-based outreach. Another major theme, which connects to the other symposium talks, was the importance of three S’s: Stigma, Shame, and Silence as cultural considerations in the African American, West African, and Latino/a/x/e communities as they apply to access to information and training to better understand AD/ADRD.

Phase 2 Results of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor As Treatment for Life-Threatening Acute Gvhd

Background: Severe organ damage from acute graft-versus-host disease (aGVHD) results in a high risk of morbidity and mortality. Treatments that focus on immunosuppression alone do not consistently improve long-term survival. Modalities that aid in inflammation resolution, immune tolerance, and tissue repair may improve outcomes beyond high-dose corticosteroids and other broad immunosuppressants for life-threatening aGVHD. We studied the addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF, Pregnyl®, Organon, USA) to standard aGVHD therapy in a prospective Phase 2 clinical trial (NCT02525029) conducted at the University of Minnesota and Rush University, extending from our previously published Phase 1 study results (Holtan et al, Blood Advances, 2020) showing uhCG/EGF to be safe and preliminarily efficacious as aGVHD therapy.Methods: Patients with new onset Minnesota (MN) high risk aGVHD (N=22) or with aGVHD requiring 2nd line therapy (N=22) received methylprednisolone 48 mg/m2/day plus 2,000 units/m2 of uhCG/EGF subcutaneously (SQ) every other day for 1 week (high risk arm). Patients in need of 2nd line aGVHD therapy received 2,000 - 5,000 units/m2 SQ every other day, with dose depending on organ severity, for 2 weeks plus standard of care immunosuppression (anti-thymocyte globulin (N=4), etanercept (N=1), ruxolitinib (N=5), sirolimus (N=4), steroid boost (N=8)). Patients who achieved a complete or partial response (CR/PR) after their initial course of therapy received twice weekly maintenance doses for the next 5 weeks. Exploratory metabolomic profiling was performed using mass spectrometry.Results: The median age was 61 years (range 2 years - 72 years, 75% male). The majority of patients had stage 3-4 lower GI GVHD (52%) and overall grade III-IV aGVHD (75%) at time of enrollment, with a median baseline albumin of 2.6 g/dl (range 0.9 - 4 g/dl) and median baseline Karnofsky performance status of 50 (range 20-100). The proportion of patients with a response (CR/PR) at day 28 (primary endpoint) was 68% (57% CR, 11% PR, Figure 1A). Among MN high risk patients receiving 1st line steroids, 64% achieved a CR at day 28 (0% PR). Among patients receiving 2nd line therapy, 50% achieved a CR and 23% PR at day 28. The median overall survival for the entire cohort was 1.2 years (Figure 1B), with a 2-year survival of 67% for responders and 12% for non-responders (p<0.01). Twenty-three died; causes of death included aGVHD (n=9), relapse (n=9), infection (n=3), and organ failure (n=2). Only one dose-limiting toxicity occurred (1 cerebral venous sinus thrombosis, resolved with anticoagulation). Exploratory metabolomic analysis of plasma samples collected during the study suggest potential correlations between blood metabolites and response to therapy. Higher levels of linoleic acid were associated with greater CR/PR rates, while higher levels of lactic acid were associated with treatment failure (Figure 1C).Conclusion: Our Phase 2 study demonstrates that uhCG/EGF is a promising addition to systemic therapy in patients with life-threatening aGVHD. The overall survival result is encouraging considering historical median survival of <0.5 years for patients with both MN high risk and steroid refractory aGVHD. As a commercially available, safe, and inexpensive drug, addition of uhCG/EGF to standard therapy may reduce morbidity and mortality from severe aGVHD. Further studies to explore its role as a steroid-sparing treatment are warranted. [Display omitted] DisclosuresHoltan: Incyte: Consultancy, Research Funding; Generon: Consultancy. Ustun: novartis: Honoraria; Blueprint: Honoraria. Arora: Pharmacyclics: Research Funding; Syndax: Research Funding; Kadmom: Research Funding. Bachanova: Incyte: Research Funding; FATE: Membership on an entity's Board of Directors or advisory committees, Research Funding; KaryoPharma: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Betts: Patent Disclosures: Patents & Royalties: B.C.B. holds a patent (WO2015120436A2) related to CD4+ T cell pSTAT3 as a marker and therapeutic target of acute GVHD. B.C.B. additionally holds a provisional patent (WO2017058950A1) related to the use of JAK inhibitors for rejection and GVHD prevention. . Vercellotti: CSL Behring: Research Funding; Mitobridge, an Astellas Company: Consultancy, Research Funding. Brunstein: GamidaCell: Research Funding; NANT: Research Funding; FATE: Research Funding; BlueRock: Research Funding; AlloVir: Consultancy. Janakiram: FATE, Nektar Therapeutics: Research Funding; Bristol Meyer Squibb, Kyowa Kirin, ADCT Therapeutics: Honoraria. Weisdorf: Fate Therapeutics: Research Funding; Incyte: Research Funding. MacMillan: Equilium: Other: DSMB member; Incyte: Consultancy; Jazz Pharmaceuticals: Consultancy. OffLabel Disclosure:uhCG/EGF has FDA orphan drug designation to treat acute GVHD.