Travers, Paul M

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.

Background: Colorectal cancer (CRC) remains one of the common causes of cancer-related morbidity and mortality in the United States. Emerging increases in early-onset CRC and persistent disparities remain major public health concerns. Objective: To characterize long-term CRC incidence and mortality trends in the United States, with particular emphasis on identifying demographic groups experiencing rising or plateauing disease burden. Methods: We conducted a population-based ecological study using CRC incidence data from the United States Cancer Statistics database (1999–2022) and mortality data from CDC WONDER (1999–2023). Temporal trends were evaluated using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC), stratified by age, sex, race/ethnicity, and urbanization level. Results: Overall CRC incidence and mortality declined during the study period (both AAPC approximately −2.08%). However, incidence increased significantly among adults younger than 55 years, particularly those aged 20–24 years. Mortality also increased among younger adults aged 25–44 years and remained elevated among individuals aged 45–54 years. Non-Hispanic Black individuals consistently experienced the highest incidence and mortality rates. Mortality declines plateaued in several older age groups after 2018–2020. Conclusions: Despite overall improvements in CRC burden, increasing incidence and mortality among younger adults and persistent disparities highlight the need for risk-stratified prevention, earlier detection strategies, and tailored therapeutic approaches.

AbstractBackground and AimAlthough fidaxomicin is an effective first‐line treatment for Clostridioides difficile infection, it has not been well studied in patients with inflammatory bowel disease. We aimed to assess the effectiveness of fidaxomicin for the treatment of C. difficile infection in patients with inflammatory bowel disease.MethodsThis was a multicenter retrospective study of adults with inflammatory bowel disease and C. difficile infection treated with fidaxomicin with at least 3 months of follow up. The primary outcomes were treatment response, defined as resolution of C. difficile infection‐attributed diarrhea and/or negative C. difficile infection stool test, and time to C. difficile infection recurrence after fidaxomicin.ResultsThirty‐three patients (median age 42 years; 60.6% female) were included. Most patients had ulcerative colitis (26, 78.8%), were receiving treatment with a biologic or small molecule medication (19, 57.6%), and had a prior episode of C. difficile infection (26, 78.8%, median 2 episodes, range 0–15). Fidaxomicin led to resolution of C. difficile infection in 20 (60.6%) patients, with 6/20 (30.0%) developing a recurrence at a median of 55 days. Most patients who failed to respond to fidaxomicin underwent fecal microbiota transplantation (10/13, 76.9%) with resolution.ConclusionsIn this cohort of patients with inflammatory bowel disease and C. difficile infection, 60.6% responded to treatment with fidaxomicin. Of those who did not respond, fecal microbiota transplantation was an effective therapy.

ABSTRACT Chronic gastrointestinal bleeding is the leading cause of iron deficiency anemia in developed countries, and most occult bleeds are attributed to upper gastrointestinal tract lesions, which are broadly categorized into mass lesions, vascular, infectious, and inflammatory abnormalities. Gastric polyps account for an exceedingly small portion of these lesions but are of clinical importance because of the risk for progression to malignancy. We describe a patient found to have a gastric foveolar-type adenoma as a rare cause of iron deficiency anemia, with an incidentally found gastric neuroendocrine tumor.

Background and Aims: Colonoscopies are routinely obtained before liver transplantation, although their utility is a highly debated topic in the literature. We aimed to determine the risk factors in patients with decompensated cirrhosis (DC) for post-colonoscopy complications (PCC). Materials and Methods: We performed a single-center retrospective study of patients with DC undergoing colonoscopy as part of their pre–liver-transplant evaluation. The primary composite outcome was defined as a complication occurring within 30 days of the colonoscopy. Complications included acute renal failure, new or worsening ascites or hepatic encephalopathy, gastrointestinal bleeding, or any cardiopulmonary or infectious complication. Logistic regression analysis was utilized to derive a risk score in predicting the primary composite outcome. Results: The strongest predictors of post-colonoscopy complication were MELD-Na ≥21 [aOR 4.0026 (P=0.0050)] and history of any infection in the 30 days before colonoscopy [aOR 8.4345 (P=0.0093)]. The area under the receiver operating characteristic curve of the final model was 0.78. The predicted risk of any complication at the lowest quartile was 16.2% to 39.4%, and the observed risk was 30.6% (95% CI: 15.5-45.6%), while the predicted risk at the highest quartile was 71.9% to 97.1%, and the observed risk was 81.3% (95% CI: 67.7-95%). Conclusion: In this cohort of patients with DC undergoing colonoscopy for pre–liver-transplant evaluation, a history of ascites, spontaneous bacterial peritonitis, and MELD-Na were found to be predictive of PCC. This risk score may help to predict PCC in patients with DC undergoing a pre-transplant colonoscopy. External validation is recommended.