Biased placement of Mitochondria fission facilitates asymmetric inheritance of protein aggregates during yeast cell division.

Mitochondria are essential and dynamic eukaryotic organelles that must be inherited during cell division. In yeast, mitochondria are inherited asymmetrically based on quality, which is thought to be vital for maintaining a rejuvenated cell population; however, the mechanisms underlying mitochondrial remodeling and segregation during this process are not understood. We used high spatiotemporal imaging to quantify the key aspects of mitochondrial dynamics, including motility, fission, and fusion characteristics, upon aggregation of misfolded proteins in the mitochondrial matrix. Using these measured parameters, we developed an agent-based stochastic model of dynamics of mitochondrial inheritance. Our model predicts that biased mitochondrial fission near the protein aggregates facilitates the clustering of protein aggregates in the mitochondrial matrix, and this process underlies asymmetric mitochondria inheritance. These predictions are supported by live-cell imaging experiments where mitochondrial fission was perturbed. Our findings therefore uncover an unexpected role of mitochondrial dynamics in asymmetric mitochondrial inheritance.

The effect of an organ procurement organization surgeon on pediatric organ utilization.

INTRODUCTION: Organ procurement organizations (OPO) have started to employ transplant-trained surgeons dedicated to organ procurement with the aim to increase allograft utilization and enhance the use of procured organs. We investigated the effects of an OPO-employed surgeon on the procurement and utilization of organs from pediatric donors within the Southwestern Transplant Alliance OPO. METHODS: OPO data were obtained for all procurements that were performed between 2014 and 2019. The analysis was performed to see if the presence of an OPO donor surgeon impacted the utilization of pediatric livers. Donor and recipient demographic data were examined between allografts procured with the presence of an OPO surgeon (OPO-Present) and those without an OPO surgeon (OPO-Absent). A p-value of <.05 was considered significant. RESULTS: Of 149 pediatric procurements, 91 included an OPO-donor surgeon. In procurements with OPO-Present, donors were younger (8.2 vs. 11.2, p < .05) and had longer distances to travel to the recipient center (334 vs. 175 miles p < .05), but had comparable cold ischemic times. In terms of organ share type, more OPO-Present livers were shared nationally and there was no difference in discard rate between OPO-Present and OPO-Absent procurements. Finally, OPO-Present livers were more likely to be transplanted to pediatric recipients compared to OPO-Absent (47.3% vs. 24.1% p < .05). CONCLUSION: The presence of an OPO surgeon has impacted organ utilization, leading to increased transplantation of pediatric livers in pediatric recipients, and has expanded the geographical share of pediatric livers.

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.

Biliary atresia and liver transplantation in the United States: A contemporary analysis.

BACKGROUND: Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown. METHODS: We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non-BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing-risk regression analysis, graft survival rates were compared using Kaplan-Meier time-to-event analysis and Cox proportional hazards modelling provided adjusted estimates. RESULTS: There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non-BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living-donor liver transplantations (LDLT) and 611 (27.7%) split deceased-donor LTs. Five-year graft survival was significantly higher among BA versus non-BA cholestatic patients in the older group (88.3% vs. 79.5%, p < .01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03-3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87-6.2). CONCLUSION: Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes.

Use of DCD organs: Expanding the donor pool to increase pediatric transplantation.

The number of children being listed for transplant continues to be greater than the number of available organs. In fact, over the past decade, rates of liver and kidney transplants in pediatric transplantation are essentially unchanged (Am J Transplant. 2020;20:193 and Am J Transplant. 2020;20:20). The use of DCD donors offers a potential solution to organ scarcity; however, the use of DCD organs in pediatric transplantation remains a rare event. Pediatric transplants done using carefully chosen DCD donor organs have shown to have outcomes similar to those seen with the use of donation after brain death (DBD) donors. Herein, we review the literature to examine the utilization of DCD livers and kidneys, outcomes of these allografts, and assess if DCD organs are a viable method to increase organ availability in pediatric transplantation.

Delayed graft function in pediatric living donor kidney transplantation.

BACKGROUND: Pediatric recipients of living donor kidneys have a low rate of delayed graft function (DGF). We examined the incidence, risk factors and outcomes of DGF in pediatric patients who received a living donor allograft. METHODS: The STARfile was queried to examine all pediatric patients transplanted with a living donor kidney between 2000 and 2020. Donor and recipient demographic data were examined, as were survival and outcomes. Recipients were stratified into DGF and no DGF groups. DGF was defined as the need for dialysis within the first week after transplant. RESULTS: 6480 pediatric patients received a living donor (LD) kidney transplant during the study period. 269 (4.2%) developed DGF post-transplant. Donors were similar in age, creatinine, and cold ischemia time. Recipients of kidneys with DGF were similar in age, sensitization status and HLA mismatch. Focal segmental glomerulosclerosis (FSGS) was the most common diagnosis in recipients with DGF, and allograft thrombosis was the most common cause of graft loss in this group. Small recipients (weight < 15 kg) were found to have a significantly higher rate of DGF. Length of stay doubled in recipients with DGF, and rejection rates were higher post-transplant. Recipients of LD kidneys who developed DGF had significantly worse 1 year allograft survival (67% vs. 98%, p < .0001). CONCLUSIONS: Pediatric living donor kidney transplant recipients who experience DGF have significantly poorer allograft survival. Optimizing the donor and recipient matching to avoid compounding risks may allow for better outcomes.

Normothermic machine perfusion for older transplant recipients.

INTRODUCTION: Elderly patients (≥65 years old) are increasingly undergoing liver transplantation and are more likely to be removed from the waitlist. Normothermic machine perfusion (NMP) holds promise in expanding the number of livers available for transplant and improving outcomes for marginal donors and recipients. We aimed to determine the impact of NMP on outcomes in elderly recipients at our institution and nationally using the UNOS database. METHODS: The use of NMP on outcomes in elderly recipients was reviewed using both the UNOS/SRTR database (2016-2022) and institutional data (2018-2020). Characteristics and clinical outcomes were compared between the NMP and static cold (control) groups within both populations. RESULTS: Nationally, using the UNOS/SRTR database, we identified 165 elderly recipients from 28 centers who received a liver allograft undergoing NMP and 4270 that underwent traditional cold static storage. NMP donors were older (48.3 vs. 43.4 years, p < 0.01), had similar rates of steatosis (8.5% vs 8.5%, p = 0.58), were more likely to be from a DCD (41.8% vs 12.3%, p < 0.01), and had a higher donor risk index (DRI; 1.70 vs. 1.60, p < 0.02). NMP recipients had similar age but had a lower MELD score at transplant (17.9 vs. 20.7, p = 0.01). Despite increased marginality of the donor graft, NMP recipients had similar allograft survival and decreased length of stay, even after accounting for recipient characteristics including MELD. Institutional data showed that 10 elderly recipients underwent NMP and 68 underwent cold static storage. At our institution, NMP recipients had a similar length of stay, rates of complications, and readmissions. CONCLUSIONS: NMP may mitigate donor risk factors that are relative contraindications for transplantation in elderly liver recipients, increasing the donor pool. The application of NMP in older recipients should be considered.

Short-term kidney transplant outcomes from severe acute respiratory syndrome coronavirus 2 lower respiratory tract positive donors.

OBJECTIVE: In this study, we aim to assess short-term allograft outcomes following deceased donor kidney transplantation from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lower respiratory tract (LRT) nucleic acid testing (NAT) positive donors. METHODS: From September to December 2021, SARS-CoV-2 NAT positive organ donors, whose solid abdominal organs were transplanted at our academic medical center were identified. Donors were stratified into having tested positive for SARS-CoV-2 in an upper respiratory tract (URT) or LRT sample. For this study, the SARS-CoV-2 LRT NAT positive deceased kidney donors and their respective recipients were examined. Donor and recipient demographic data, coronavirus disease 2019 (COVID-19)-related history, patient outcomes, as well as postoperative graft function were evaluated. RESULTS: Thirteen SARS-CoV-2 positive deceased donors were identified. Of these, eight were LRT NAT positive and yielded nine kidneys. These allografts were successfully transplanted into vaccinated and unvaccinated recipients. All recipients received standard induction immunosuppression and did not receive any prophylactic therapy for SARS-CoV-2. Two recipients had delayed graft function. At 1-month post-transplant, there was no clinical evidence of donor-derived COVID-19 or graft loss, and all recipients were free from dialysis. CONCLUSION: We describe the first case series of SARS-CoV-2 LRT NAT positive deceased kidney donors for vaccinated and unvaccinated recipients with excellent short-term allograft outcomes and no clinical evidence of donor-derived COVID-19 post-transplantation. Given the increasing prevalence of SARS-CoV-2 in the population, utilization of SARS-CoV-2 LRT NAT positive deceased donors could be considered an acceptable source of organs for renal transplantation, especially as multi-center experiences and longer-term follow-up emerge.

Normothermic Machine Perfusion in pediatric liver transplantation: A survey of attitudes and barriers.

BACKGROUND: NMP provides a superior strategy for the assessment and preservation of marginal donor livers and has demonstrated increased utilization and enhances organ quality when used in adult liver transplantation. We aimed to evaluate the interest of incorporating the use of NMP in pediatric liver transplantation. METHODS: An anonymous online survey was distributed to pediatric transplant surgeons and hepatologists across the United States. Respondent demographic information, attitudes toward NMP in pediatric liver transplantation, and barriers to utilization were examined. RESULTS: Thirty-two providers (18 transplant surgeons and 14 hepatologists) completed the survey, yielding a response rate of 64%. Half (50%) of respondents indicated prior exposure to NMP. Overall, 96% of respondents believed there was benefit to using NMP in pediatric liver transplantation. DCD (68%) and post-cross-clamp (75%) grafts were the greatest opportunity for NMP use. A role in splitting livers ex vivo (71%) was also seen as a potential major opportunity. Cost was perceived as a barrier to implementation (36%), followed by institutional factors (32%). Cost tolerance was significantly greater in respondents residing in OPTN regions with greater than median wait times (63% vs. 11% in OPTN regions with greater vs. shorter wait times, p = .010). CONCLUSIONS: There is significant interest within the pediatric liver transplant community for NMP to expand the donor pool. Interest appears particularly strong in regions where wait times for suitable pediatric donors are prolonged.

Simultaneous ex vivo normothermic preservation of liver and heart grafts from a donation after circulatory death donor.

Normothermic machine perfusion of organs is growing in popularity and has been used for both abdominal and thoracic organ preservation before transplantation. The use of normothermic machine perfusion for donation after cardiac death organs can reduce cold ischemia time and help prevent ischemia-related complications. We present a successful case of a donation after cardiac death procurement with both liver and heart allografts preserved by normothermic machine perfusion. Both allografts were perfused without complications and transplanted successfully. As the technology continues to become more prevalent, the situation described will become more commonplace, and we offer a view of the future in transplantation.

Liver Transplantation in the Time of a Pandemic: A Widening of the Racial and Socioeconomic Health Care Gap During COVID-19.

OBJECTIVE: During the initial wave of the COVID-19 pandemic, organ transplantation was classified a CMS Tier 3b procedure which should not be postponed. The differential impact of the pandemic on access to liver transplantation was assessed. SUMMARY BACKGROUND DATA: Disparities in organ access and transplant outcomes among vulnerable populations have served as obstacles in liver transplantation. METHODS: Using UNOS STARfile data, adult waitlisted candidates were identified from March 1, 2020 to November 30, 2020 (n = 21,702 pandemic) and March 1, 2019 to November 30, 2019 (n = 22,797 pre-pandemic), and further categorized and analyzed by time periods: March to May (Period 1), June to August (Period 2), and September to November (Period 3). Comparisons between pandemic and pre-pandemic groups included: Minority status, demographics, diagnosis, MELD, insurance type, and transplant center characteristics. Liver transplant centers (n = 113) were divided into tertiles by volume (small, medium, large) for further analyses. Multivariable logistic regression was fitted to assess odds of transplant. Competing risk regression was used to predict probability of removal from the waitlist due to transplantation or death and sickness. Additional temporal analyses were performed to assess changes in outcomes over the course of the pandemic. RESULTS: During Period 1 of the pandemic, Minorities showed greater reduction in both listing (-14% vs -12% Whites), and transplant (-15% vs -7% Whites), despite a higher median MELD at transplant (23 vs 20 Whites, P < 0.001). Of candidates with public insurance, Minorities demonstrated an 18.5% decrease in transplants during Period 1 (vs -8% Whites). Although large programs increased transplants during Period 1, accounting for 61.5% of liver transplants versus 53.4% pre-pandemic (P < 0.001), Minorities constituted significantly fewer transplants at these programs during this time period (27.7% pandemic vs 31.7% pre-pandemic, P = 0.04). Although improvements in disparities in candidate listings, removals, and transplants were observed during Periods 2 and 3, the adjusted odds ratio of transplant for Minorities was 0.89 (95% CI 0.83-0.96, P = 0.001) over the entire pandemic period. CONCLUSIONS: COVID-19's effect on access to liver transplantation has been ubiquitous. However, Minorities, especially those with public insurance, have been disproportionately affected. Importantly, despite the uncertainty and challenges, our systems have remarkable resiliency, as demonstrated by the temporal improvements observed during Periods 2 and 3. As the pandemic persists, and the aftermath ensues, health care systems must consciously strive to identify and equitably serve vulnerable populations.

Comparison of Clinical Outcomes of Induction Regimens in Patients Undergoing Liver Transplantation for Acute Liver Failure.

Spontaneous survival rates in acute liver failure (ALF) are vastly improved by liver transplantation (LT). However, the value of induction agents beyond steroids continues to be debated. To understand the potential benefit of different induction regimens in the ALF population, we compared overall survival of recipients undergoing LT in the United States for ALF. Using the Scientific Registry of Transplant Recipients, we assessed the impact of induction immunosuppression (IS) in a cohort of 3754 first-time LT recipients with a diagnosis of ALF from 2002 to 2018. Induction IS therapy was grouped into steroid-only induction, use of antithymocyte globulin (ATG), or interleukin 2 receptor antibody. Other regimens were excluded from analysis. Survival analysis was estimated via Cox proportional hazards models and expressed as hazard ratios (HRs). In LT for ALF, the use of induction agents beyond steroids is increasingly frequent over the last 2 decades. The use of ATG is associated with worse overall survival, even after adjusting for donor and recipient factors, with HR of 1.24 (95% confidence interval, 1.00-1.53; P = 0.05). An elevated serum creatinine, recipient and donor age, and Black ethnicity, were all associated with reduced survival, whereas maintenance IS with calcineurin inhibitors (CNIs) was associated with improved survival. Although adjunct induction therapy has become more common, our analysis shows that compared with a steroid-only induction regimen, the addition of ATG is associated with worse overall survival after LT for ALF. CNI maintenance was highly protective, suggesting that an IS strategy focusing on corticosteroid-only induction followed by CNI maintenance may offer the best overall survival rate.

Making Every Liver Count: Increased Transplant Yield of Donor Livers Through Normothermic Machine Perfusion.

OBJECTIVE: Normothermic machine perfusion (NMP) enables optimized ex-vivo preservation of a donor liver in a normal physiologic state. The impact of this emerging technology on donor liver utilization has yet to be assessed. SUMMARY BACKGROUND DATA: NMP of the donor liver and ex-vivo enhancement of its function has been envisioned for decades, however only with recent technological advances have devices been suitable for transition to clinical practice. The present study examines the effect NMP on liver utilization in the United States. METHODS: The United Network for Organ Sharing database was queried to identify deceased donor livers procured from 2016 to 2019 (n = 30596). Donor livers were divided by preservation method: standard cold-static preservation (COLD, n = 30,368) versus NMP (n = 228). Donor and recipient risk factors, liver disposition, and discard reasons were analyzed. The primary outcome was liver discard rate between 2 groups. RESULTS: A total of 4037 livers were discarded. The NMP group had a 3.5% discard rate versus 13.3% in the COLD group (P < 0.001), and this was despite NMP donors being older (47.7 vs 39.5 years, P < 0.0001), more frequently donation after cardiac death (DCD) (18% vs 7%, P < 0.001), and having a greater donor risk index (1.6 vs 1.5, P < 0.05). The most common reasons for liver discard in the COLD group were biopsy findings (38%), DCD warm ischemic time (11%), and prolonged preservation time (10%). Survival analysis, following propensity score matching, found no significant difference in 1-year overall survival between recipients of NMP versus COLD livers. CONCLUSIONS: NMP reduces the discard rate of procured livers despite its use in donors traditionally considered of more marginal quality. NMP maintains excellent graft and patient survival. Broader application of NMP technology holds the potential to generate a significant number of additional liver grafts for transplantation every year, thus greatly reducing the nationwide disparity between supply and demand.

Trends in utilization of deceased donor kidneys based on hepatitis C virus status and impact of public health service labeling on discard.

BACKGROUND: Kidneys from deceased donors infected with hepatitis C virus (HCV) are underutilized. Most HCV virus-infected donors are designated as Public Health Service increased donors (PHS-IR). Impact of PHS and HCV designations on discard is not well studied. METHODS: We queried the UNOS data set for all deceased donor kidneys between January 2015 and December 2018. The final study cohort donors (n = 38 702) were stratified into three groups based on HCV antibody (Ab) and NAT status: (a) Ab-/NAT- (n = 35 861); (b) Ab+/NAT- (n = 973); and (c) Ab±/NAT+ (n = 1868). We analyzed utilization/discard rates of these organs, the impact of PHS-IR and HCV designations on discard using multivariable two-level hierarchical logistic regression models, forecasted number of HCV viremic donors/kidneys by 2023. RESULTS: During the study period, (a) the number of viremic donor kidneys increased 2 folds; (b) the multilevel mixed-effects logistic regression models showed that, overall, the PHS labeling (OR 1.20, CI 95% CI 1.15-1.29) and HCV designation (OR 2.29; 95% CI 2.15-2.43) were independently associated with increased risk of discard; (c) contrary to the general perception, PHS-IR kidneys across all HCV groups, compared to PHS-IR kidneys were more likely to be discarded; (d) we forecasted that the number of kidneys from HCV viremic donor kidneys might increase from 1376 in 2019 to 2092 in 2023. CONCLUSION: Hepatitis C virus viremic kidneys might represent 10%-15% of deceased donor organ pool soon with the current rate of the opioid epidemic. PHS labeling effect on discard requires further discussion of the utility of this classification.

Donation after cardiac death kidneys are suitable for pediatric recipients.

Despite the high number of children listed for kidney transplantation and shortage of deceased organ donors, there is reluctance to utilize DCD kidneys in pediatric recipients. We examined outcomes in pediatric kidney transplant patients who received a DCD kidney allograft. UNOS database was queried to examine outcomes in all pediatric kidney transplant recipients from 1994 to 2017. Pediatric status was defined as <18 years at the time of transplantation. Recipients were divided by DBD or DCD allograft status. Donor and recipient demographic data were examined. Patient and allograft survival was calculated, and Kaplan-Meier survival curves were generated. A P-value of <0.05 was considered to be significant. A total of 286 pediatric kidney transplant recipients received a DCD allograft. The donors in the DCD group were significantly younger than those in the DBD group (21.7 vs 23.3 years), with a higher KDPI (26.5% vs 22.9%). In the DCD group, the average age at transplant was younger (11.6 vs 12.9 years), with no difference in cold ischemia time or length of stay between the two groups. Rates of delayed graft function were higher in the DCD group, but despite this, there were no significant differences in allograft or patient survival between the groups. There is no difference in allograft survival in pediatric kidney transplant recipients who receive a DCD kidney allograft. DCD kidney allografts are suitable for transplantation in pediatric patients and can greatly expand the donor pool.

Should more donation after cardiac death livers be used in pediatric transplantation?

INTRODUCTION: There is a mismatch that exists in donor liver organ supply and demand. DCD livers represents a potential source to increase the number of liver grafts available for use in pediatric recipients; however, there has been hesitancy to use such organs. We evaluated patient and allograft outcomes in pediatric liver transplant recipients of DCD livers. METHODS: The UNOS database was queried to examine outcomes in all liver transplant recipients from 1993 to 2017. Patients were then divided according to adult and pediatric status, DBD or DCD allograft status, and era of transplant. Donor and recipient demographic data were examined, and patient and allograft survival were calculated. A P-value of <0.05 was considered to be significant. RESULTS: A total of 57 pediatric recipients received a DCD liver allograft. DCD recipients were older than DBD recipients. There was no difference in the final PELD score between the groups. There were no differences in causes of allograft failure between the DCD and DBD groups. Importantly, the overall allograft survival in the DCD and DBD groups was similar, as was allograft survival based on era. CONCLUSION: Pediatric liver transplant recipients of DCD allografts have comparable patient and allograft survival when compared to DBD allograft recipients. Use of DCD allografts in the pediatric liver transplant population should be strongly considered to increase the donor organ pool.

Utilizing increased risk for disease transmission (IRD) kidneys for pediatric renal transplant recipients.

BACKGROUND: Strategies to expand numbers of deceased donor kidneys suitable for pediatric recipients are urgently needed to prevent long-term dialysis-associated morbidity and mortality. Donors designated as increased risk of disease transmission (IRD) are infrequently used in pediatric recipients. We examined outcomes of these kidneys in pediatric patients and the potential to increase the donor pool. METHODS: The United Network for Organ Sharing (UNOS) database records presence of IRD in all deceased donors since 2004. All pediatric kidney transplant recipients from 2004 to 2017 were identified and stratified by IRD status, and outcomes were examined. RESULTS: Four hundred seventy-three pediatric kidney transplant recipients received an IRD allograft. IRD donors had lower kidney donor profile index (KDPI); were more likely to be younger, male, and Caucasian; and were more likely to have used drugs. IRD kidneys were more likely to have been biopsied and placed on pulsatile perfusion. Other than an older recipient age, demographic data were not different between groups. Allograft and patient survivals were similar, as were rejection and delayed graft function rates. Compared with adult recipients and adult IRD recipients, pediatric recipients were more likely to have a younger donor, receive a kidney with a lower creatinine, and were less likely to have delayed graft function (p < 0.05). There were no recorded disease transmissions in IRD group. CONCLUSIONS: Patient and allograft survivals are similar in IRD and non-IRD kidneys. High-quality IRD organs used in adults represent a large number of donors with excellent outcomes. IRD allografts have a potential to increase transplant volume and should be considered for pediatric patients.

Attenuation of insulin signalling contributes to FSN-1-mediated regulation of synapse development.

A neuronal F-box protein FSN-1 regulates Caenorhabditis elegans neuromuscular junction development by negatively regulating DLK-mediated MAPK signalling. In the present study, we show that attenuation of insulin/IGF signalling also contributes to FSN-1-dependent synaptic development and function. The aberrant synapse morphology and synaptic transmission in fsn-1 mutants are partially and specifically rescued by reducing insulin/IGF-signalling activity in postsynaptic muscles, as well as by reducing the activity of EGL-3, a prohormone convertase that processes agonistic insulin/IGF ligands INS-4 and INS-6, in neurons. FSN-1 interacts with, and potentiates the ubiquitination of EGL-3 in vitro, and reduces the EGL-3 level in vivo. We propose that FSN-1 may negatively regulate insulin/IGF signalling, in part, through EGL-3-dependent insulin-like ligand processing.

Increased risk of vascular thrombosis in pediatric liver transplant recipients with thrombophilia.

BACKGROUND: Pediatric patients who undergo liver transplantation are at higher risk of developing vascular complications when compared to adult liver transplant recipients. The consequences of hepatic artery thrombosis (HAT) or portal vein thrombosis (PVT) can cause significant morbidity and mortality. We examined pediatric liver transplant recipients who developed vascular thrombosis and the presence of thrombophilia. METHODS: We examined outcome in all pediatric patients who underwent liver transplantation. Recipient, donor demographic data, and outcome data were examined. Categorical differences were compared using the unpaired Student t-test and nominal variables using either the chi-square or the Fischer exact test. A P value of <0.05 was considered significant. RESULTS: Forty-six pediatric patients underwent liver transplantation. Twenty-one recipients were found to have thrombophilia, including 5 with HAT and 2 with PVT. When comparing recipients with or without any vascular thrombosis, those with thrombophilia had a significantly higher incidence of developing a vascular thrombosis (7/21 versus 0/25, P = 0.0017). Five of 42 recipients with artery-to-artery reconstruction developed HAT versus 0 of 4 with a conduit. Recipients who developed any thrombosis were significantly lower in weight than those who did not develop any thrombosis (9.0 ± 1.6 kg versus 22.2 ± 16.0 kg, P = 0.0366). CONCLUSIONS: All pediatric liver transplant recipients who developed any vascular thrombosis were also found to have thrombophilia. Recipients who were smaller in size were at significantly higher risk of developing vascular thrombosis. Lower weight recipients with thrombophilia may benefit from arterial reconstruction with a conduit to decrease the risk of vascular thrombosis.