Matching Patients to Accelerate Clinical Trials (MPACT): Enabling Technology for Oncology Clinical Trial Workflow.

Clinical trial enrollment is impeded by the significant time burden placed on research coordinators screening eligible patients. With 50,000 new cancer cases every year, the Veterans Health Administration (VHA) has made increased access for Veterans to high-quality clinical trials a priority. To aid in this effort, we worked with research coordinators to build the MPACT (Matching Patients to Accelerate Clinical Trials) platform with a goal of improving efficiency in the screening process. MPACT supports both a trial prescreening workflow and a screening workflow, employing Natural Language Processing and Data Science methods to produce reliable phenotypes of trial eligibility criteria. MPACT also has a functionality to track a patient's eligibility status over time. Qualitative feedback has been promising with users reporting a reduction in time spent on identifying eligible patients.

Building Research Infrastructure to Develop Greater Learning Efficiencies (BRIDGE).

In this manuscript, we outline our developed version of a Learning Health System (LHS) in oncology implemented at the Department of Veterans Affairs (VA). Transferring healthcare into an LHS framework has been one of the spearpoints of VA's Central Office and given the general lack of evidence generated through randomized control clinical trials to guide medical decisions in oncology, this domain is one of the most suitable for this change. We describe our technical solution, which includes a large real-world data repository, a data science and algorithm development framework, and the mechanism by which results are brought back to the clinic and to the patient. Additionally, we propose the need for a bridging framework that requires collaboration between informatics specialists and medical professionals to integrate knowledge generation into the clinical workflow at the point of care.

First Report of Neofusicoccum mediterraneum and Neofusicoccum parvum Causing Pine Ghost Canker on Pinus spp. in Southern California.

Pinus eldarica, P. halepensis and P. radiata are important conifer species native to Mediterranean regions that are cultivated in the southwestern United States for landscaping (Phillips and Gladfelter, 1991; Chambel et al., 2013). Among them, Monterey pine (P. radiata) is native to restricted areas of California and Mexico, but it is extensively grown for timber production in other countries, especially in the Southern Hemisphere (Rogers, 2004). From 2018 to 2022, severe dieback and cankers have been detected on more than 30 mature pines of the three species within a 40-ha urban forest in Orange County, Southern California. Symptoms initiate on the lower portion of the canopy and advance into the crown, leading to quick dieback and, in some cases, to tree death. Cross sections of affected branches revealed wedged cankers with irregular, indistinct margins, and cryptic discoloration (i.e., "ghost cankers"). Pycnidia were observed on the surface of each bark scale of branches with advanced infections. Two morphotypes of Botryosphaeriaceae colonies (n = 34 isolates) were recovered consistently from more than 90% of the symptomatic pines. Two isolates per morphotype were grown on pistachio leaf agar (Chen et al., 2014) for 14 days to induce pycnidia formation. Conidia (n = 50) were hyaline, thin-walled and fusoid to ellipsoidal in shape, ranging from 16.1 to 27.9 (22.6) × 5.4 to 8.2 (6.8) µm for the first morphotype and 11.5 to 20.4 (16.3) × 4.8 to 8.6 (6.3) µm for the second morphotype. The rDNA internal transcribed spacer (ITS), beta-tubulin (tub2), and translation elongation factor 1-alpha (tef1-α) partial gene regions were amplified and sequenced using the primers ITS5/ITS4 (White et al., 1990), Bt2a/Bt2b (Glass and Donaldson, 1995), and EF1-728F/EF1-986R (Carbone and Kohn, 1999), respectively. A multi-locus phylogenetic analysis revealed that isolates UCD9433 and UCD10439 clustered with the ex-type strain of Neofusicoccum mediterraneum (CBS:113083), and isolates UCD9161 and UCD9434 grouped with N. parvum (CMW:9081). Sequences were submitted to GenBank (nos. OP535391 to OP535394 for ITS, OP561946 to OP561949 for tef1-α, and OP561950 to OP561953 for tub2). Pathogenicity tests were performed with above-mentioned isolates on 20-mm-diameter healthy branches of mature Monterey pines (n = 10, 14 years old) located in a research field at UC Davis. Isolates were grown for 7 days on potato dextrose agar and inoculated in the internode area by removing a 5-mm-diameter disk of the bark with a sterile cork borer and placing a 5-mm-diameter mycelial plug. Controls were mock-inoculated with sterile agar plugs, and the experiment was performed twice. After three months, inoculations resulted in vascular lesions that ranged from 20.6 to 49.7 (32.7) mm with N. mediterraneum and from 13.5 to 71.0 (33.6) mm with N. parvum, and the same pathogens were reisolated (70 to 100% recovery). Controls remained symptomless and no botryosphaeriaceous colonies were recovered. Both N. mediterraneum and N. parvum are polyphagous pathogens associated with multiple woody plant hosts (Phillips et al., 2013). Previously, only N. parvum has been associated with pine cankers in Iran, however, the pine species was not indicated (Abdollahzadeh et al., 2013). The detection of these pathogens in urban forests raises concerns of potential spillover events to other forest and agricultural hosts in Southern California. To our knowledge, this is the first report of N. mediterraneum and N. parvum causing Pine Ghost Canker on P. eldarica, P. halepensis and P. radiata.

Serum albumin and risks of hospitalization and death: Findings from the Atherosclerosis Risk in Communities study.

OBJECTIVES: To determine whether lower serum albumin in community-dwelling, older adults is associated with increased risk of hospitalization and death independent of pre-existing disease. DESIGN: Prospective cohort study of participants in the fifth visit of the Atherosclerosis Risk in Communities (ARIC) study. Baseline data were collected from 2011 to 2013. Follow-up was available to December 31, 2017. Replication was performed in Geisinger, a health system in rural Pennsylvania. SETTING: For ARIC, four US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburbs of Minneapolis, Minnesota. PARTICIPANTS: A total of 4947 community-dwelling men and women aged 66 to 90 years. EXPOSURE: Serum albumin. MAIN OUTCOMES: Incident all-cause hospitalization and death. RESULTS: Among the 4947 participants, mean age was 75.5 years (SD: 5.12) and mean baseline serum albumin concentration was 4.05 g/dL (SD: 0.30). Over a median follow-up period of 4.42 years (interquartile interval: 4.16-5.05), 553 participants (11.2%) died and 2457 participants (49.7%) were hospitalized at least once. The total number of hospitalizations was 5725. In analyses adjusted for demographics and numerous clinical characteristics, including tobacco use, obesity, frailty, cardiovascular disease, kidney disease, diabetes C-reactive protein (CRP), cognitive status, alcohol use, medication use, respiratory disease, and systolic blood pressure, 1 g/dL lower baseline serum albumin concentration was associated with higher risk of both hospitalization (incidence rate ratio [IRR]: 1.58; 95% confidence interval [CI]: 1.36-1.82; p < 0.001) and death (hazard ratio [HR]: 1.67; 95% CI: 1.24-2.24; p < 0.001). Associations were weaker with older age but not different by frailty status or level of high-sensitivity CRP. Associations between serum albumin, hospitalizations, and death were also similar in a real-world cohort of primary care patients. CONCLUSIONS: Lower baseline serum albumin was significantly associated with increased risk of both all-cause hospitalization and death, independent of pre-existing disease. Older adults with low serum albumin should be considered a high-risk population and targeted for interventions to reduce the risk of adverse outcomes.

The National Cancer Institute and Department of Veterans Affairs Interagency Group to Accelerate Trials Enrollment (NAVIGATE): A federal collaboration to improve cancer care.

Cancer clinical trials represent an important option for patients with a diagnosis of cancer and the clinician-investigators involved in their care who seek options for their disease. For all who are impacted by cancer, these studies offer opportunities for greater learning. Conducting these important studies involves several challenges, including recruiting eligible participants. To address barriers that arise over the course of these activities, the Department of Veterans Affairs (VA) and National Cancer Institute (NCI) have partnered to increase Veteran participation in oncology clinical trials. This initiative, the NCI And VA Interagency Group to Accelerate Trials Enrollment, or NAVIGATE, is focused on addressing recruitment across the VA healthcare system and finding systematic solutions related to activating, recruiting for and conducting oncology clinical trials at VA Medical Centers. Additional goals include (1) establishing a sustainable network that can serve as a model for other VA sites interested in doing cancer clinical trials, (2) recruitment of minority patients, and (3) developing best practices and policies that can be deployed across the VA healthcare system. In this manuscript, we describe the scope, organization, activities, and future directions of NAVIGATE while also highlighting key needs for successfully conducting cancer clinical trials within the VA system. This partnership between 2 large federal agencies with a shared commitment to improving cancer care may provide lessons to others who are also dedicated to helping those affected by the disease.

The VA Point-of-Care Precision Oncology Program: Balancing Access with Rapid Learning in Molecular Cancer Medicine.

The Department of Veterans Affairs (VA) recognized the need to balance patient-centered care with responsible creation of generalizable knowledge on the effectiveness of molecular medicine tools. Embracing the principles of the rapid learning health-care system, a new clinical program called the Precision Oncology Program (POP) was created in New England. The POP integrates generalized knowledge about molecular medicine in cancer with a database of observations from previously treated veterans. The program assures access to modern genomic oncology practice in the veterans affairs (VA), removes disparities of access across the VA network of clinical centers, disseminates the products of learning that are generalizable to non-VA settings, and systematically presents opportunities for patients to participate in clinical trials of targeted therapeutics.

Identification, pathogenicity and abundance of Paracremonium pembeum sp. nov. and Graphium euwallaceae sp. nov.--two newly discovered mycangial associates of the polyphagous shot hole borer (Euwallacea sp.) in California.

Fusarium euwallaceae is a well-characterized fungal symbiont of the exotic ambrosia beetle Euwallacea sp. (polyphagous shot hole borer [PSHB]), together inciting Fusarium dieback on many host plants in Israel and California. Recent discoveries of additional fungal symbionts within ambrosia beetle mycangia suggest these fungi occur as communities. Colony-forming units of Graphium euwallaceae sp. nov. and Paracremonium pembeum sp. nov., two novel fungal associates of PSHB from California, grew from 36 macerated female heads and 36 gallery walls collected from Platanus racemosa, Acer negundo, Persea americana and Ricinus communis. Fungi were identified based on micromorphology and phylogenetic analyses of the combined internal transcribed spacer region (nuc rDNA ITS1-5.8S-ITS2 [ITS barcode]), elongation factor (EF 1-α), small subunit (18S rDNA) sequences for Graphium spp., ITS, EF 1-α, calmodulin (cmdA), large subunit of the ATP citrate lyase (acl1), ß-tubulin (tub2), RNA polymerase II second largest subunit (rpb2) and large subunit (28S rDNA) sequences for Paracremonium spp. Other Graphium spp. recovered from PSHB in Vietnam, Euwallacea fornicatus in Thailand, E. validus in Pennsylvania and Paracremonium sp. recovered from PSHB in Vietnam were identified. F. euwallaceae was recovered from mycangia at higher frequencies and abundances in all hosts except R. communis, in which those of F. euwallaceae and P. pembeum were equal. P. pembeum was relatively more abundant within gallery walls of A. negundo and R. communis. In all hosts combined F. euwallaceae was relatively more abundant within PSHB heads than gallery walls. All three fungi grew at different rates and colonized inoculated excised stems of P. americana and A. negundo. P. pembeum produced longer lesions than F. euwallaceae and G. euwallaceae on inoculated avocado shoots. Results indicate PSHB is associated with a dynamic assemblage of mycangial fungal associates that pose additional risk to native and nonnative hosts in California.

Implementation of a Precision Oncology Program as an Exemplar of a Learning Health Care System in the VA.

The program determines and disseminates precision oncology best practices; enhances patient and provider engagement; and fosters collaboration among the VA, National Cancer Institute, academia, other health care systems, and industry to provide cancer patients with access to clinical trial participation.

Host Range of Fusarium Dieback and Its Ambrosia Beetle (Coleoptera: Scolytinae) Vector in Southern California.

The polyphagous shot hole borer (PSHB) is an invasive ambrosia beetle that forms a symbiosis with a new, as-yet-undescribed Fusarium sp., together causing Fusarium dieback on avocado and other host plants in California and Israel. In California, PSHB was first reported on black locust in 2003 but there were no records of fungal damage until 2012, when a Fusarium sp. was recovered from the tissues of several backyard avocado trees infested with PSHB in Los Angeles County. The aim of this study was to determine the plant host range of the beetle-fungus complex in two heavily infested botanical gardens in Los Angeles County. Of the 335 tree species observed, 207 (62%), representing 58 plant families, showed signs and symptoms consistent with attack by PSHB. The Fusarium sp. was recovered from 54% of the plant species attacked by PSHB, indicated by the presence of the Fusarium sp. at least at the site of the entry hole. Trees attacked by PSHB included 11 species of California natives, 13 agriculturally important species, and many common street trees. Survey results also revealed 19 tree species that function as reproductive hosts for PSHB. Additionally, approximately a quarter of all tree individuals planted along the streets of southern California belong to a species classified as a reproductive host. These data suggest the beetle-disease complex potentially may establish in a variety of plant communities locally and worldwide.