Clift, Kristin E

Ex vivo liver perfusion (EVLP) sustains human or large animal livers outside the body under near-physiological conditions, enabling functional monitoring for lactate clearance, bile production, and oxygen consumption and allowing targeted therapeutic interventions. Originally developed to optimize donor grafts for transplantation, EVLP has evolved into a powerful translational research platform bridging preclinical discovery and early clinical translation. This review discusses EVLP as a platform for gene therapy, immunotherapy, pharmacology, and personalized medicine, with particular emphasis on gene- and immune-based interventions as mechanistically mature exemplars. We consolidate advances in pharmacological testing and toxicity modeling, viral and non-viral gene delivery, genome engineering, and immunomodulation using perfused livers. We further describe emerging applications, including autologous EVLP pathways for organ-confined therapy, ex vivo liver surgery, and bioengineering strategies such as biliary organoid repair, RNA interference, and mitochondrial transfer. We highlight how these applications align with a paradigm shift in biomedical research, including the NIH’s recent initiative to prioritize human-based experimental models over animal-only studies. By leveraging transplant-declined or surgically resected organs that would otherwise be unused, ex vivo perfusion bridges the gap between pre-clinical testing and clinical practice, enabling real-time evaluation of interventions in functional human tissue. We discuss both the scientific opportunities afforded by EVLP and the technical, biosafety, and ethical challenges that must be addressed to enable responsible clinical translation.

PURPOSE Guidelines recommend germline genetic testing (GT) for patients with pancreatic ductal adenocarcinoma (PDAC). This study aims to evaluate the utilization and outcomes of multigene panel GT in patients with PDAC. METHODS This retrospective, multisite study included patients with PDAC diagnosed between May 2018 and August 2020 at Mayo Clinic Arizona, Florida, and Minnesota. Discussion, uptake, and outcomes of GT were compared before (May 1, 2018-May 1, 2019) and after (August 1, 2019-August 1, 2020) the guideline update, accounting for a transition period. RESULTS The study identified 533 patients with PDAC, with 321 (60.2%) preguideline and 212 (39.8%) postguideline. Patient characteristics did not differ between the preguideline and postguideline periods. GT was discussed in 34.3% (110 of 321) of preguideline and 39.6% (84 of 212) of postguideline patients (odds ratio [OR], 1.26 [95% CI, 0.88 to 1.80]) and subsequently performed in 80.9% (89 of 110) of preguideline and 75.0% (63 of 84) of postguideline patients (OR, 1.10 [95% CI, 0.75 to 1.61]). Of 152 tested patients, 26 (17.1%) had a pathogenic variant (PV), of whom 17 (11.2%; 17 of 152) were PDAC-associated. Over the entire study period, GT was more likely in younger patients (65 v 70 years; P < .001), those seen by a medical oncologist (82.9% v 69.0%; P < .001), and those surviving more than 12 months from diagnosis (70.4% v 43.4%; P < .001). Demographics and personal/family cancer history were comparable between patients with and without a PDAC PV. CONCLUSION GT remains underutilized despite National Comprehensive Cancer Network guideline recommendations. Given the poor prognosis of PDAC and potential implications of GT, efforts to increase utilization are needed to provide surveillance and support to both patients with PDAC and at-risk family members.

Introduction: The COVID-19 pandemic has disproportionally affected historically marginalized populations and their access to resources and healthcare. In times of crisis, authentic community engagement is more important than ever. This study was Phase 1 of a larger 3-phase study to conduct timely community-engaged research with community members to understand the disproportionate impact of COVID-19 on historically underserved communities. The objective of this work was to conduct key informant (KI) interviews (1) to understand community organizations perspectives about the role that large academic health centers play as they interface with community organizations to support their work, (2) to leverage KI’s expertise to identify needs and assets within the community, and (3) to inform both Phase 2 (focus group qualitative research) and Phase 3 (survey) of the broader study. Methods: A total of 24 key informants were identified through purposeful sampling and one-on-one semi-structured interviews were conducted across 4 states using video conferencing. Results: Barriers to access and lack of transparency were highlighted as major issues requiring reform—in particular, aggressive billing practices and insurance barriers exacerbated local distrust of medical institutions. KIs recognized the health institution’s support for testing and vaccination during the COVID-19 pandemic, but noted other significant gaps in care, especially regarding mental health support. Although communication with the health institution was consistent for some KIs, others experienced unsustained communication efforts that hindered cooperation and relationship building. Conclusions: Leaders in the community as key stakeholders can provide unique insights into the challenges and potential solutions required to promote health equity, and foster understanding between local communities and healthcare institutions.

Introduction: Family health history can be a valuable indicator of risk to develop certain cancers. Unfortunately, patient self-reported family history often contains inaccuracies, which might change recommendations for cancer screening. We endeavored to understand the difference between a patient’s self-reported family history and their electronic medical record (EMR) family history. One aim of this study was to determine if family history information contained in the EMR differs from patient-reported family history collected using a focused questionnaire. Methods: We created the Hereditary Cancer Questionnaire (HCQ) based on current guidelines and distributed to 314 patients in the Department of Family Medicine waiting room June 20 to August 1, 2018. The survey queried patients about specific cancers within their biological family to assess their risk of an inherited cancer syndrome. We used the questionnaire responses as a baseline when comparing family histories in the medical record. Results: Agreement between the EMR and the questionnaire data decreased as the patients’ risk for familial cancer increased. Meaning that the more significant a patient’s family cancer history, the less likely it was to be recorded accurately and consistently in the EMR. Patients with low-risk levels, or fewer instances of cancer in the family, had more consistencies between the EMR and the questionnaire. Conclusions: Given that physicians often make recommendations on incomplete information that is in the EMR, patients might not receive individualized preventive care based on a more complete family cancer history. This is especially true for individuals with more complicated and significant family history of cancer. An improved method of collecting family history, including increasing patient engagement, may help to decrease this disparity.