Anti-apoptotic treatment of warm ischemic male rat livers in machine perfusion improves symptoms of ischemia-reperfusion injury.

Background: Liver donation after cardiac death (DCD) makes up a small percentage of the organs used in transplantation and poses a higher risk of graft loss compared to donation after brain death (DBD); this is a result of ischemia reperfusion for which the exact injury mechanisms are currently not fully understood. However, reperfusion injury has been shown to lead to necrosis as well as apoptosis through oxidative stress and mitochondrial dysfunction. In this work, we propose that use of the pro-survival, anti-apoptotic CEPT cocktail in post-ischemia normothermic machine perfusion (NMP) may improve recovery in rat livers subjected to extended durations of warm ischemia. Materials and Methods: Livers procured from male Lewis rats were subjected to 90 min of warm ischemia, followed by 6 h of NMP where they were treated either with the survival-enhancing anti-apoptotic cocktail (CEPT), the vehicle (DMSO) or the base media with no additives. Results: The CEPT-treated group exhibited lower expression of hepatic injury biomarkers, and improvement in a range of hepatocellular symptoms associated with the hepatic parenchyma, biliary epithelium and the sinusoidal endothelium, including recovery of bile secretion and lowered vascular resistance. Conclusions: This study's findings suggest apoptosis plays a more significant role in ischemia-reperfusion injury than previously understood, and provide useful insight for further investigation of the specific underlying mechanisms and development of novel treatment methods.

Acellular Perfusate is an Adequate Alternative to Packed Red Blood Cells During Normothermic Human Kidney Perfusion.

Background: Brief normothermic machine perfusion is increasingly used to assess and recondition grafts before transplant. During normothermic machine perfusion, metabolic activity is typically maintained using red blood cell (RBC)-based solutions. However, the utilization of RBCs creates important logistical constraints. This study explored the feasibility of human kidney normothermic perfusion using William's E-based perfusate with no additional oxygen carrier. Methods: Sixteen human kidneys declined for transplant were perfused with a perfusion solution containing packed RBCs or William's E medium only for 6 h using a pressure-controlled system. The temperature was set at 37 °C. Renal artery resistance, oxygen extraction, metabolic activity, energy metabolism, and histological features were evaluated. Results: Baseline donor demographics were similar in both groups. Throughout perfusion, kidneys perfused with William's E exhibited improved renal flow (P = 0.041) but similar arterial resistance. Lactic acid levels remained higher in kidneys perfused with RBCs during the first 3 h of perfusion but were similar thereafter (P = 0.95 at 6 h). Throughout perfusion, kidneys from both groups exhibited comparable behavior regarding oxygen consumption (P = 0.41) and reconstitution of ATP tissue concentration (P = 0.55). Similarly, nicotinamide adenine dinucleotide levels were preserved during perfusion. There was no evidence of histological damage caused by either perfusate. Conclusions: In human kidneys, William's E medium provides a logistically convenient, off-the-shelf alternative to packed RBCs for up to 6 h of normothermic machine perfusion.

Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21.

Dietary restriction promotes resistance to surgical stress in multiple organisms. Counterintuitively, current medical protocols recommend short-term carbohydrate-rich drinks (carbohydrate loading) prior to surgery, part of a multimodal perioperative care pathway designed to enhance surgical recovery. Despite widespread clinical use, preclinical and mechanistic studies on carbohydrate loading in surgical contexts are lacking. Here we demonstrate in ad libitum-fed mice that liquid carbohydrate loading for one week drives reductions in solid food intake, while nearly doubling total caloric intake. Similarly, in humans, simple carbohydrate intake is inversely correlated with dietary protein intake. Carbohydrate loading-induced protein dilution increases expression of hepatic fibroblast growth factor 21 (FGF21) independent of caloric intake, resulting in protection in two models of surgical stress: renal and hepatic ischemia-reperfusion injury. The protection is consistent across male, female, and aged mice. In vivo, amino acid add-back or genetic FGF21 deletion blocks carbohydrate loading-mediated protection from ischemia-reperfusion injury. Finally, carbohydrate loading induction of FGF21 is associated with the induction of the canonical integrated stress response (ATF3/4, NF-kB), and oxidative metabolism (PPARγ). Together, these data support carbohydrate loading drinks prior to surgery and reveal an essential role of protein dilution via FGF21.

Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.

Effect of Donor Age and Liver Steatosis on Potential of Decellularized Liver Matrices to be used as a Platform for iPSC-Hepatocyte Culture.

Decellularization of discarded whole livers and their recellularization with patient-specific induced pluripotent stem cells (iPSCs) to develop a functional organ is a promising approach to increasing the donor pool. The effect of extracellular matrix (ECM) of marginal livers on iPSC-hepatocyte differentiation and function has not been shown. To test the effect of donor liver ECM age and steatosis, young and old, as well as no, low, and high steatosis livers, are decellularized. All livers are decellularized successfully. High steatosis livers have fat remaining on the ECM after decellularization. Old donor liver ECM induces lower marker expression in early differentiation stages, compared to young liver ECM, while this difference is closed at later stages and do not affect iPSC-hepatocyte function significantly. High steatosis levels of liver ECM lead to higher albumin mRNA expression and secretion while at later stages of differentiation expression of major cytochrome (CYP) 450 enzymes is highest in low steatosis liver ECM. Both primary human hepatocytes and iPSC-hepatocytes show an increase in fat metabolism marker expression with increasing steatosis levels most likely induced by excess fat remaining on the ECM. Overall, removal of excess fat from liver ECM may be needed for inducing proper hepatic function after recellularization.

Impact of Median MELD at Transplant Minus 3 National Policy on Quality of Transplanted Livers for Patients With and Without Hepatocellular Carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) have been overprioritized in the deceased donor liver allocation system. The United Network for Organ Sharing adopted a policy in May 2019 that limited HCC exception points to the median Model for End-Stage Liver Disease at transplant in the listing region minus 3. We hypothesized this policy change would increase the likelihood to transplant marginal quality livers into HCC patients. METHODS: This was a retrospective cohort study of a national transplant registry, including adult deceased donor liver transplant recipients with and without HCC from May 18, 2017, to May 18, 2019 (prepolicy) to May 19, 2019, to March 1, 2021 (postpolicy). Transplanted livers were considered of marginal quality if they met ≥1 of the following: (1) donation after circulatory death, (2) donor age ≥70, (3) macrosteatosis ≥30% and (4) donor risk index ≥95th percentile. We compared characteristics across policy periods and by HCC status. RESULTS: A total of 23 164 patients were included (11 339 prepolicy and 11 825 postpolicy), 22.7% of whom received HCC exception points (prepolicy versus postpolicy: 26.1% versus 19.4%; P = 0.03). The percentage of transplanted donor livers meeting marginal quality criteria decreased for non-HCC (17.3% versus 16.0%; P < 0.001) but increased for HCC (17.7% versus 19.4%; P < 0.001) prepolicy versus postpolicy. After adjusting for recipient characteristics, HCC recipients had 28% higher odds of being transplanted with marginal quality liver independent of policy period (odds ratio: 1.28; confidence interval, 1.09-1.50; P < 0.01). CONCLUSIONS: The median Model for End-Stage Liver Disease at transplant in the listing region minus 3 policy limited exception points and decreased the quality of livers received by HCC patients.

Single-center experience with early liver transplantation for acute alcohol-related hepatitis-Limitations of the SALT score and directions for future study.

Alcohol-related liver disease (ALD) is the leading indication for liver transplantation worldwide. Since Mathurin et al. described their experience in providing early liver transplantation for patients with ALD in 2011, other centers have followed suit with generally favorable survival outcomes. This patient population poses a unique clinical challenge given the expedited nature of the evaluation and the lack of any significant sobriety period prior to transplantation. The SALT (Sustained Alcohol Use Post-Liver Transplant) score is a standardized psychometric tool increasingly used to help stratify the risk of relapse and guide listing decisions for these challenging clinical situations. In 2018, our center introduced a protocol for early liver transplantation for acute alcohol-related hepatitis (AAH). In this article, we offer a retrospective review of 26 patients transplanted between May 2018 and May 2021, including at least 1-year follow-up, and compare outcomes to initial SALT scores; we further identify additional factors that may impact post-transplant success. As transplant committees continue to weigh the ethical dilemma of denying lifesaving treatment against the obligation to remain stewards of a limited resource, we aim to contribute to a more nuanced understanding of risk regarding early transplantation for ALD.

Sex-based Disparities in Access to Liver Transplantation for Waitlisted Patients With Model for End-stage Liver Disease Score of 40.

OBJECTIVE: To determine the association of sex with access to liver transplantation among candidates with the highest possible model for end-stage liver disease score (MELD 40). BACKGROUND: Women with end-stage liver disease are less likely than men to receive liver transplantation due in part to MELD's underestimation of renal dysfunction in women. The extent of the sex-based disparity among patients with high disease severity and equally high MELD scores is unclear. METHODS: Using national transplant registry data, we compared liver offer acceptance (offers received at match MELD 40) and waitlist outcomes (transplant vs death/delisting) by sex for 7654 waitlisted liver transplant candidates from 2009 to 2019 who reached MELD 40. Multivariable logistic and competing-risks regression was used to estimate the association of sex with the outcome and adjust for the candidate and donor factors. RESULTS: Women (N = 3019, 39.4%) spent equal time active at MELD 40 (median: 5 vs 5 days, P = 0.28) but had lower offer acceptance (9.2% vs 11.0%, P < 0.01) compared with men (N = 4635, 60.6%). Adjusting for candidate/donor factors, offers to women were less likely accepted (odds ratio = 0.87, P < 0.01). Adjusting for candidate factors, once they reached MELD 40, women were less likely to be transplanted (subdistribution hazard ratio = 0.90, P < 0.01) and more likely to die or be delisted (subdistribution hazard ratio = 1.14, P = 0.02). CONCLUSIONS: Even among candidates with high disease severity and equally high MELD scores, women have reduced access to liver transplantation and worse outcomes compared with men. Policies addressing this disparity should consider factors beyond MELD score adjustments alone.

Sodium Hydrosulfide Treatment During Porcine Kidney Ex Vivo Perfusion and Transplantation.

Background: In rodents, hydrogen sulfide (H2S) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of H2S are conserved in pigs, a more clinically relevant model. Methods: Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion. Kidney perfusion was evaluated with dynamic contrast-enhanced MRI. MRI spectroscopy was further employed to assess energy metabolites including ATP. Renal biopsies were collected at various time points for histopathological analysis. Results: Perfusion for 4 h pig kidneys with Belzer MPS UW + NaHS resulted in similar renal perfusion and ATP levels than perfusion with UW alone. Similarly, no difference was observed when NaHS was administered in the renal artery before ischemia. After autotransplantation, no improvement in histologic lesions or cortical/medullary kidney perfusion was observed upon H2S administration. In addition, AMP and ATP levels were identical in both groups. Conclusions: In conclusion, treatment of porcine kidney grafts using NaHS did not result in a significant reduction of ischemia-reperfusion injury or improvement of kidney metabolism. Future studies will need to define the benefits of H2S in human, possibly using other molecules as H2S donors.

Transition from stromatolite to thrombolite fabric: potential role for reticulopodial protists in lake microbialites of a Proterozoic ecosystem analog.

Prior observations suggest that foraminiferan protists use their reticulopodia (anastomosing pseudopodia) to alter sediment fabric by disrupting laminations of subtidal marine stromatolites, erasing the layered structures in an experimental setting. Because microbialites and foraminifera are found in non-marine settings, we hypothesized that foraminifera living in lakes could also disrupt layered microbialite fabric. With this aim and using a variety of multidisciplinary approaches, we conducted field surveys and an experiment on microbialites from Green Lake (GL; Fayetteville, New York State, United States), which has been studied as a Proterozoic ecosystem analog. The lake is meromictic and alkaline, receiving calcium sulfate-rich water in the monimolimnion; it supports a well-developed carbonate platform that provides access to living and relict microbialites. The living microbialites grow from early spring to autumn, forming a laminated mat at their surface (top ~5 mm), but a clotted or massive structure exists at depth (> ~ 1 cm). We observed a morphotype of "naked" foraminiferan-like protist in samples from GL microbialites and sediments; thus, considered the possibility of freshwater foraminiferan impact on microbialite fabric. Results of an experiment that seeded the cultured freshwater foraminifer Haplomyxa saranae onto the GL microbialite surface indicates via micro-CT scanning and anisotropy analysis that the introduced foraminifer impacted uppermost microbialite layering (n = 3 cores); those cores with an added inhibitor lacked changes in anisotropy for two of those three cores. Thus, it remains plausible that the much smaller, relatively common, native free-form reticulate protist, which we identified as Chlamydomyxa labyrinthuloides, can disrupt microbialite fabrics on sub-millimeter scales. Our observations do not exclude contributions of other possible causal factors.

Anti-apoptotic treatment of warm ischemic male rat livers in machine perfusion improves symptoms of ischemia-reperfusion injury.

Liver donation after cardiac death (DCD) makes up a small percentage of the donor pool and poses a higher risk of graft loss compared to donation after brain death (DBD); this is a result of ischemia reperfusion for which the exact injury mechanisms are currently not fully understood. However, reperfusion injury has been shown to lead to necrosis as well as apoptosis at the cellular level. In this work, we propose that use of the pro-survival, anti-apoptotic CEPT cocktail in post-ischemia normothermic machine perfusion (NMP) may improve recovery in rat livers subjected to extended durations of warm ischemia. Livers procured from male lewis rats were subjected to 90 minutes of warm ischemia, followed by 6 hours of NMP where they were treated with the survival-enhancing anti-apoptotic cocktail (CEPT), the vehicle (DMSO) or the base media with no additives. The CEPT-treated group exhibited lower expression of hepatic injury biomarkers, and improvement in a range of hepatocellular functions associated with the hepatic parenchyma, biliary epithelium and especially the sinusoidal endothelium. This study's findings provide useful insight for further investigation of the extent of apoptotic contribution to ischemia reperfusion injury (IRI).

Impact of Portable Normothermic Machine Perfusion for Liver Transplantation From Adult Deceased Donors.

OBJECTIVE: To assess how liver allografts preserved using portable normothermic machine perfusion (NMP) compare against those that underwent ischemic cold storage (ICS) in the setting of donation after brain death (DBD) and donation after circulatory death (DCD) liver transplantation (LT). BACKGROUND: Compared with conventional ICS, NMP may offer more homeostatic preservation, permit physiological assessment of organ function, and provide opportunities for graft improvement/modification. We report a single-center US experience of liver NMP. METHODS: A single-center, retrospective analysis of collected data on 541 adult whole LTs from 469 DBD donors [NMP (n = 58) vs ICS (n = 411)] and 72 DCD donors [NMP (n = 52) vs ICS (n = 20)] between January 2016 and December 2022. RESULTS: In DBD LT, male sex [odds ratio (95% CI): 1.83 (1.08-3.09)] and >10% macrosteatosis of the donor liver [1.85 (1.10-3.10)] were statistically significant independent risk factors of early allograft dysfunction (EAD). Donor age >40 years and cold ischemia time >7 hours were independent risk factors of reperfusion syndrome (RPS). One-year, 3-year, and 5-year incidences of ischemic cholangiopathy (IC) did not differ significantly in DBD cases between the NMP and ICS cohorts. In DCD LT, NMP was an independent protective factor against EAD [0.11 (0.03-0.46)] and RPS [0.04 (0.01-0.25)]. The incidence of IC in the DCD cases at 1-year and 3-year time points was significantly lower in the NMP cohort (1.9% compared with 20% in the ICS group). CONCLUSIONS: Compared with conventional ICS, NMP can significantly reduce the incidence of EAD, RPS, and IC after DCD LT.

Preferred language and disease severity predict evaluation for liver transplantation among patients admitted with alcohol-associated hepatitis.

BACKGROUND: Liver transplantation (LT) for alcohol-associated hepatitis (AH) is a relatively new practice and limited work exists surrounding the role social determinants of health may play in evaluation. This includes language that defines how patients interact with the healthcare system. We explored characteristics of patients with AH evaluated for LT within an integrated health system. METHODS: Using a system-wide registry, we identified admissions for AH from 1 January 2016 to 31 July 2021. A multivariable logistic regression model was developed to evaluate independent predictors of LT evaluation. RESULTS: Among 1723 patients with AH, 95 patients (5.5%) underwent evaluation for LT. Evaluated patients were more likely have English as their preferred language (95.8% vs 87.9%, P = 0.020), and had higher INR (2.0 vs 1.4, P < 0.001) and bilirubin (6.2 vs 2.9, P < 0.001). AH patients who underwent evaluation had a lower burden of mood and stress disorders (10.5% vs 19.2%, P < 0.05). Patients with English preferred language had a greater than three times adjusted odds of LT evaluation compared with all others when adjusting for clinical disease severity, insurance status, sex, and psychiatric comorbid conditions (OR, 3.20; 95% CI, 1.14-9.02). CONCLUSION: Patients with AH evaluated for LT were more likely to have English as their preferred language, more psychiatric comorbidities, and more severe liver disease. Despite adjustment for psychiatric comorbidities and disease severity, English preferred language remained the strongest predictor of evaluation. As programs expand LT for AH, it is vital to build equitable systems that account for the interaction between language and healthcare in transplantation.

Donor-derived disorders of hemostasis and thrombosis in liver transplantation: Considerations for deceased donor liver selection.

OLT is known to be associated with a precarious perioperative hemostatic state due to dysregulation of procoagulant and anticoagulant factors, endothelial injury, and inflammation. Transmission of inherited bleeding and clotting disorders from the liver donor to the recipient may further complicate hemostasis during and after transplantation. As a result, consideration of congenital coagulation disorders in the liver donor is a practical concern for donor selection. However, there is no clear consensus regarding the selection of donors with known or suspected thrombophilia or bleeding disorders. While multiple case reports and retrospective studies, subject to reporting bias, describe donor-derived thrombophilic and bleeding disorders, there are no large-scale studies in the adult liver transplant literature that examine the frequency of transmission, utility of donor screening, or clinical impact of donor hemostatic disorders. Based on the reported literature, we summarize our approach for donor selection with an aim to balance improved organ utility and optimal post-transplant outcomes.

Impact of donor sex on hepatocellular carcinoma recurrence in liver transplantation after brain death.

BACKGROUND: Hepatocellular carcinoma (HCC) is predominantly seen in males but has a better prognosis in females. No prior studies have investigated HCC recurrence based on sex combination following liver transplant donated after brain death (DBDLT). This study sought to elucidate the effects of donor and recipient sex on HCC recurrence rates. METHODS: 9232 adult recipients from the United Network for Organ Sharing (UNOS) database who underwent DBDLT for HCC from 2012 to 2018 were included. Donor-recipient pairs were divided into (1) female donor/female recipient (F-F) (n = 1089); (2) male donor/female recipient (M-F) (n = 975); (3) female donor/male recipient (F-M) (n = 2691); (4) male donor/male recipient (M-M) (n = 4477). The primary prognostic outcome was HCC recurrence. A multivariable competing risk regression analysis was used to assess prognostic influences. RESULTS: The median recipient age and model for end-stage liver disease (MELD) scores were similar among the four groups. Livers of male recipients demonstrated greater in size and number of HCC (both p-values were <.0001). There was also a higher rate of vascular invasion in male recipients compared to female (p < .0001). Competing risk analyses showed that the cumulative HCC recurrence rate was significantly lower in the M-F group (p = .013). After adjusting for tumor characteristics, liver grafts from male donors were associated with a lower HCC recurrence rate in female recipients (HR: .62 95%CI: .42-.93) (p = .021). CONCLUSION: In DBDLT, male donor to female recipient pairing exhibited lower HCC recurrence rates. SUMMARY: Lowest rates of HCC recurrence were confirmed among the female recipients of male donor grafts group in the deceased donor LT cohort. A competing risk multivariable regression analysis demonstrated that male donor sex was significantly associated with low HCC recurrence in female but not male recipients.

Alterations in Cytoskeleton and Mitochondria in the Development and Reversal of Steatosis in Human Hepatocytes.

BACKGROUND & AIMS: Alterations in mitochondrial morphology and function and increased oxidative stresses in hepatocytes are well established in nonalcoholic fatty liver disease (NAFLD). Patients can undergo lifestyle changes, especially in earlier NAFLD stages, to reverse disease-induced phenotypes on a gross level. Yet, little is known about whether mitochondrial function and injuries recover upon reversal. Thus, we elucidated this question and interplays between the cytoskeletal network and mitochondria in the development and reversal of steatosis. METHODS: We cultured primary human hepatocytes stably for 2 weeks and used free fatty acid supplementation to induce steatosis over 7 days and reversed steatosis by free fatty acid withdrawal over the next 7 days. We assessed cytoskeletal and mitochondrial morphologies using immunocytochemistry and confocal microscopy. We evaluated mitochondrial respiration and function via the Seahorse analyzer, in which we fully optimized reagent dosing specifically for human hepatocytes. RESULTS: During early steatosis, intracellular lipid droplets displaced microtubules altering mitochondrial distribution, and disrupted the F-actin network, leading to loss of bile canaliculi in steatotic hepatocytes. Basal mitochondrial respiration, maximum respiratory capacity, and resistance to H2O2-induced cell death also increased as an adaptative response. Upon reversal of steatosis, F-actin and bile canaliculi were restored in hepatocytes. Nevertheless, we observed an increase in elongated mitochondrial branches accompanied by decreases in α-tubulin expression, mitochondrial proton leak, and susceptibility to H2O2-induced cell death. CONCLUSIONS: Despite the restoration of cytoskeletons morphologically upon reversal of steatosis, the mitochondria in hepatocytes were impaired owing to early adaptative respiratory increase. Hepatocytes thus were highly predisposed to H2O2-induced cell death. These results indicate the persistence of potential health risks for recovering NAFLD patients.

Continuous versus Pulsatile Flow in 24-Hour Vascularized Composite Allograft Machine Perfusion in Swine: A Pilot Study.

INTRODUCTION: Multiple perfusion systems have been investigated on vascularized composite allografts, with various temperatures and different preservation solutions, most using continuous flow (CF). However, physiological flow is pulsatile and provides better outcomes in kidney and lung ex vivo perfusions. The objective of this pilot study is to compare pulsatile flow (PF) with CF in our 24-h subnormothermic machine perfusion protocol for swine hindlimbs. METHODS: Partial hindlimbs were harvested from Yorkshire pigs and perfused with a modified Steen solution at 21°C for 24 h either with CF (n = 3) or with pulsatile flow (PF) at 60 beats/min (n = 3). Perfusion parameters, endothelial markers, and muscle biopsies were assessed at different timepoints. RESULTS: Overall, lactate levels were significantly lower in the PF group (P = 0.001). Glucose uptake and potassium concentration were similar in both groups throughout perfusion. Total nitric oxide levels were significantly higher in the PF group throughout perfusion (P = 0.032). Nitric oxide/endothelin-1 ratio also tends to be higher in the PF group, reflecting a potentially better vasoconductivity with PF, although not reaching statistical significance (P = 0.095). Arterial resistances were higher in the PF group (P < 0.001). Histological assessment did not show significant difference in muscular injury between the two groups. Weight increased quicker in the CF group but reached similar values with the PF after 24 h. CONCLUSIONS: This pilot study suggests that PF may provide superior preservation of vascularized composite allografts when perfused for 24 h at subnormothermic temperatures, with potential improvement in endothelial function and decreased ischemic injury.

The Effect of Language on Access to Timely COVID-19 Vaccination of Solid Abdominal Organ Transplant Recipients.

In dynamic healthcare environments including the COVID-19 pandemic, it is paramount to communicate health recommendations expediently and clearly. Research has shown social determinants of health affect the impact of COVID-19 on abdominal transplant recipients, but there has been less research on the effect of language proficiency. This is a cohort study of time to first COVID-19 vaccination among abdominal organ transplant recipients in an academic medical center in Boston, MA between 18 December 2020, and 15 February 2021. Cox proportional hazards analysis of time to vaccination by preferred language were adjusted for race, age group, insurance, and transplanted organ. Among 3001 patients, 53% were vaccinated during the study period. Language preference other than English was independently associated with delay to vaccination (0.64, p = 0.001), on adjusted analysis. In addition, Black, Hispanic and other race patients were less likely to be vaccinated than white patients (0.58, 0.67, 0.68 vs. reference, all p < 0.03). Language preference other than English is an independent barrier to solid abdominal organ transplant recipients' access to timely COVID-19 vaccination. Equity in care should be improved by providing targeted services to minority language speakers.

COVID-19 infection and vaccination rarely impact HLA antibody profile in waitlisted renal transplant candidates- a multicenter cohort.

Although rare, infection and vaccination can result in antibodies to human leukocyte antigens (HLA). We analyzed the effect of SARS-CoV-2 infection or vaccination on HLA antibodies in waitlisted renal transplant candidates. Specificities were collected and adjudicated if the calculated panel reactive antibodies (cPRA) changed after exposure. Of 409 patients, 285 (69.7 %) had an initial cPRA of 0 %, and 56 (13.7 %) had an initial cPRA > 80 %. The cPRA changed in 26 patients (6.4 %), 16 (3.9 %) increased, and 10 (2.4 %) decreased. Based on cPRA adjudication, cPRA differences generally resulted from a small number of specificities with subtle fluctuations around the borderline of the participating centers' cutoff for unacceptable antigen listing. All five COVID recovered patients with an increased cPRA were female (p = 0.02). In summary, exposure to this virus or vaccine does not increase HLA antibody specificities and their MFI in approximately 99 % of cases and 97 % of sensitized patients. These results have implications for virtual crossmatching at the time of organ offer after SARS-CoV-2 infection or vaccination, and these events of unclear clinical significance should not influence vaccination programs.