Multinational Analysis of Marginal Liver Grafts Based on the Eurotransplant Extended Donor Criteria.

OBJECTIVE: To evaluate the outcome of marginal liver grafts based on the Eurotransplant extended donor criteria (ECD) criteria. SUMMARY BACKGROUND DATA: Eurotransplant uses a broad definition of ECD criteria (age >65 years, steatosis >40%, BMI >30 kg/m2, ICU stay >7 days, DCD, and certain laboratory parameters) for allocating organs to recipients who have consented to marginal grafts. Historically, marginal liver grafts were associated with increased rates of dysfunction. METHODS: Retrospective cohort analysis using the German Transplant Registry (GTR) and the US Scientific Registry of Transplant Recipients (SRTR) from 2006-2016. Results were validated with recent SRTR data (2017-2022). Donors were classified according to the Eurotransplant ECD criteria, DCD was excluded. Data were analyzed with cut-off prediction, binomial logistic regression, and multivariate Cox regression. RESULTS: The study analyzed 92,330 deceased brain-dead donors (87% SRTR) and 70,374 transplants (87% SRTR) in adult recipients. Predominant ECD factors were donor age in Germany (30%) and BMI in the US (28%). Except for donor age, grafts meeting ECD criteria were not associated with impaired 1- or 3-year survival. Cut-offs had little to no predictive value for 30-day graft survival (AUROC 0.49 - 0.52) and were nominally higher for age (72 vs. 65 years) in Germany as compared to those defined by current Eurotransplant criteria. CONCLUSIONS: The outcome of transplanted grafts from higher risk donors was nearly equal to standard donors with Eurotransplant criteria failing to predict survival of marginal grafts. Modifying ECD criteria could improve graft allocation and potentially expand the donor pool.

Abnormal Liver Biopsies of Donor Grafts in Pediatric Liver Transplantation: How Do They Fare?

BACKGROUND Little is known about outcomes of pediatric patients transplanted using donor liver grafts with abnormal biopsy results. We assessed donor liver biopsy data to report characteristics and outcomes of abnormal livers transplanted in pediatric patients. MATERIAL AND METHODS We identified pediatric patients who received a liver transplant from a biopsied deceased donor between 2015 and 2022 using the national database UNOS Standard Transplant Analysis and Research files. Recipients were excluded if they received multi-organ transplants or were lost to follow-up. Livers with ≤5% macrosteatosis, no fibrosis, and no inflammation were classified as normal livers (NL). Allografts with >5% macrosteatosis, any fibrosis, or any inflammation were considered abnormal livers (AL). Donor and recipient demographic data and outcomes were examined. RESULTS Of the 3808 total pediatric liver transplants in the study period, there were 213 biopsied donor liver allografts transplanted into pediatric recipients. Of those, 114 were NL and 99 were AL. 35.4% (35/99) of the AL had >5% macrosteatosis with a mean of 7.6±11.4%, 64.6% (64/99) had any inflammation, and 18.2% (18/99) had any fibrosis. AL donors were significantly older than NL donors. AL recipients had higher PELD scores. There were no significant differences in length of stay, rejection rates and causes, or allograft survival between AL and NL. Multivariable analysis revealed that inflammation was independently associated with a significantly greater risk for graft failure. CONCLUSIONS Outcomes of abnormal livers are excellent. Inflammation was an independent risk factor for poor graft prognosis. Donor biopsies in pediatric liver transplantation can be a useful adjunct to assess outcomes.

A contemporary analysis of 20,086 deceased donor liver biopsies.

BACKGROUND: Pre-transplant deceased donor liver biopsy may impact decision making; however, interpretation of the results remains variable and depends on accepting center practice patterns. METHODS: In this cohort study, adult recipients from 04/01/2015-12/31/2020 were identified using the UNOS STARfile data. The deceased donor liver biopsies were stratified by risk based on degree of fibrosis, macrovesicular fat content, and level of portal infiltration (low-risk: no fibrosis, no portal infiltrates, and <30% macrosteatosis; moderate-risk: some fibrosis or mild infiltrates and <30% macrosteatosis; high-risk: most fibrosis, moderate/marked infiltrates, or ≥30% macrosteatosis). Graft utilization, donor risk profile, and recipient outcomes were compared across groups. RESULTS: Of the 51,094 donor livers available, 20,086 (39.3%) were biopsied, and 34,606 (67.7%) were transplanted. Of the transplanted livers, 14,908 (43.1%) were biopsied. The transplanted grafts had lower mean macrovesicular fat content (9.3% transplanted vs. 26.9% non-transplanted, P < 0.001) and less often had any degree of fibrosis (20.9% vs. 39.9%, P < 0.001) or portal infiltration (51.3% vs. 58.2%, P < 0.001) versus non-transplanted grafts. Post-transplant recipient LOS (14.2 days high-risk vs. 15.2 days low-risk, P = 0.170) and 1-year graft survival (90.5% vs. 91.7%, P = 0.137) did not differ significantly between high- versus low-risk groups. Kaplan-Meier survival estimates further revealed no differences in the 5-year graft survival across risk strata (P = 0.833). Of the 5178 grafts biopsied and turned down, PSM revealed 1338 (26.0%) were potentially useable based on biopsy results and donor characteristics. CONCLUSION: Carefully matched deceased donor livers with some fibrosis, inflammation, or steatosis ≥30% may be suitable for transplantation. Further study of this group of grafts may decrease turndowns of potentially useable organs.

Interpersonal violence affecting the pediatric population: Patterns of injury and recidivism.

PURPOSE: We aim to describe interpersonal violence-related injury patterns in the pediatric trauma population and to identify predictors of recidivism. METHODS: In this retrospective analysis from a single institution, we included pediatric patients (≤17 years) treated (2006-2020) for traumatic injury related to interpersonal violence (IPV). Patient characteristics were compared among mechanism types and between recidivists and non recidivists using two sample t-tests, Wilcoxon rank-sum tests, and Pearson's chi-squared. Multivariate analysis was performed using logistic regression to identify predictors of repeat injury. RESULTS: We identified 635 pediatric patients who sustained injuries owning to IPV: firearm (N = 266), assault (stab/blunt; N = 243), and abuse (N = 126). The average age of the firearm, assault, and abuse groups was 15.5, 14.7, and 1.1 years (SD = 2.2, 3.4, 2.4 years), respectively. Majority of the overall cohort was male (77.5%) and publicly- or un insured (67.8%), with 28.0% being Black. Of the 489 firearm and assault patients who survived the first injury, 30 (6.1%) had repeat injury owning to IPV requiring treatment at our center with a median time of 40 months (IQR 17-62 months) between first and second injury. The majority of recidivists (83.3%) were victims of gun violence whereas the distribution between assault and firearm in the non recidivists was more even at 51 and 49%, respectively (p < 0.001). Eighteen (60.0%) of the recidivist patients had the same mechanism between the first and second injury. In the logistic regression analysis, Black race and firearm injury were associated with greater than 3-fold higher likelihood of repeat injury compared to white race after adjusting for age, sex, insurance, and child opportunity index. CONCLUSIONS: We found that survivors of firearm injuries and assault comprise a vulnerable patient cohort at risk for repeat injury, and Black race is an independent predictor of repeat injury owning to IPV. These findings provide guidance for developing violence prevention programs. TYPE OF STUDY: Retrospective Comparative Study LEVEL OF EVIDENCE: Level III.

Is there value in volume? An assessment of liver transplant practices in the United States since the inception of MELD.

BACKGROUND: Liver transplantation has increased in volume and provides substantial survival benefit. However, there remains a need for value-based assessment of this costly procedure. METHODS: Model for end stage liver disease era adult recipients were identified using United Network for Organ Sharing Standard Transplant Analysis file data (n = 75,988) and compared across time periods (period A: February 2002 to January 2007; B: February 2007 to January 2013; C: February 2013 to January 2019). Liver centers were divided into volume tertiles for each period (small, medium, large). Value for the index transplant episode was defined as percentage graft survival ≥1 year divided by mean posttransplant duration of stay. RESULTS: All centers increased value over time due to ubiquitous improvement in 1-year graft survival. However, large centers demonstrated the most significant value change (large +17% vs small +7.0%, P < .001) due to a -8.5% reduction in large centers duration of stay from period A to C, while small centers duration of stay remained unchanged (-0.1%). Large centers delivered higher value despite more complex care: older recipients (54.8 ± 10.3 vs 53.0 ± 11.4 years P < .001), fewer model for end stage liver disease exceptions (34.0% vs 38.2%, P < .001), higher rates of candidate portal vein thrombosis (10.1% vs 8.5%, P < .001) and prior abdominal surgery (43.4% vs 37.4%, P < .001), and more marginal donor utilization (donor risk index 1.45 ± 0.38 vs 1.36 ± 0.33, P < .001). Mahalanobis metric matching demonstrated that compared with small centers, large centers progressively shortened recipient duration of stay per transplant in each period (A: -0.36 days, P = .437; B: -2.14 days, P < .001; C: -2.49 days, P < .001). CONCLUSION: There is value in liver transplant volume. Adoption of value-based practices from large centers may allow optimization of health care delivery for this costly procedure.

Rational design of fiber forming supramolecular structures.

Recent strides in the development of multifunctional synthetic biomimetic materials through the self-assembly of multi-domain peptides and proteins over the past decade have been realized. Such engineered systems have wide-ranging application in bioengineering and medicine. This review focuses on fundamental fiber forming α-helical coiled-coil peptides, peptide amphiphiles, and amyloid-based self-assembling peptides; followed by higher order collagen- and elastin-mimetic peptides with an emphasis on chemical / biological characterization and biomimicry.

Highly angiogenic peptide nanofibers.

Major limitations of current tissue regeneration approaches using artificial scaffolds are fibrous encapsulation, lack of host cellular infiltration, unwanted immune responses, surface degradation preceding biointegration, and artificial degradation byproducts. Specifically, for scaffolds larger than 200-500 µm, implants must be accompanied by host angiogenesis in order to provide adequate nutrient/waste exchange in the newly forming tissue. In the current work, we design a peptide-based self-assembling nanofibrous hydrogel containing cell-mediated degradation and proangiogenic moieties that specifically address these challenges. This hydrogel can be easily delivered by syringe, is rapidly infiltrated by cells of hematopoietic and mesenchymal origin, and rapidly forms an extremely robust mature vascular network. Scaffolds show no signs of fibrous encapsulation and after 3 weeks are resorbed into the native tissue. These supramolecular assemblies may prove a vital paradigm for tissue regeneration and specifically for ischemic tissue disease.

A nanostructured synthetic collagen mimic for hemostasis.

Collagen is a major component of the extracellular matrix and plays a wide variety of important roles in blood clotting, healing, and tissue remodeling. Natural, animal derived, collagen is used in many clinical applications but concerns exist with respect to its role in inflammation, batch-to-batch variability, and possible disease transfection. Therefore, development of synthetic nanomaterials that can mimic the nanostructure and properties of natural collagen has been a heavily pursued goal in biomaterials. Previously, we reported on the design and multihierarchial self-assembly of a 36 amino acid collagen mimetic peptide (KOD) that forms nanofibrous triple helices that entangle to form a hydrogel. In this report, we utilize this nanofiber forming collagen mimetic peptide as a synthetic biomimetic matrix useful in thrombosis. We demonstrate that nanofibrous KOD synthetic collagen matrices adhere platelets, activate them (indicated by soluble P-selectin secretion), and clot plasma and blood similar to animal derived collagen and control surfaces. In addition to the thrombotic potential, THP-1 monocytes incubated with our KOD collagen mimetic showed minimal proinflammatory cytokine (TNF-α or IL-1ß) production. Together, the data presented demonstrates the potential of a novel synthetic collagen mimetic as a hemostat.