Early Graft Survival Research Articles

Impact of Medicaid expansion on kidney transplantation in the State Oklahoma.

There is no data evaluating the impact of Medicaid expansion on kidney transplants (KT) in Oklahoma. To investigate the impact of Medicaid expansion on KT patients in Oklahoma. The UNOS database was utilized to evaluate data pertaining to adult KT recipients in Oklahoma in the pre-and post-Medicaid eras. Bivariate analysis, Kaplan Meier analysis was used to estimate, and cox proportional models were utilized. There were 2758 pre- and 141 recipients in the post-Medicaid expansion era. Post-expansion patients were more often non-United States citizens (2.3% vs 5.7%), American Indian, Alaskan, or Pacific Islander (7.8% vs 9.2%), Hispanic (7.4% vs 12.8%), or Asian (2.5% vs 8.5%) (P < 0.0001). Waitlist time was shorter in the post-expansion era (410 vs 253 d) (P = 0.0011). Living donor rates, pre-emptive transplants, re-do transplants, delayed graft function rates, kidney donor profile index values, panel reactive antibodies levels, and insurance types were similar. Patients with public insurance were more frail. Despite increased early (< 6 months) rejection rates, 1-year patient and graft survival were similar. In Cox proportional hazards model, male sex, American Indian, Alaskan or Pacific Islander race, public insurance, and frailty category were independent risk factors for death at 1 year. Medicaid expansion was not associated with graft failure or patient survival (adjusted hazard ratio: 1.07; 95%CI: 0.26-4.41). Medicaid expansion in Oklahoma is associated with increased KT access for non-White/non-Black and non-United States citizen patients with shorter wait times. 1-year graft and patient survival rates were similar before and after expansion. Medicaid expansion itself was not independently associated with graft or patient survival outcomes. Ongoing research is necessary to determine the long-term effects of Medicaid expansion.

The impact of donor-recipient age difference on graft survival after heart transplant in adults with congenital heart disease

BackgroundThe impact of donor-recipient age difference in adult congenital heart disease (ACHD) patients undergoing heart transplant (HT) is unknown. MethodsACHD patients (≥18 years old) who underwent HT (2000-2020) were identified using the United Network for Organ Sharing database. Graft survival through 10 years based on donor-recipient age difference was evaluated by comparing outcomes of donors >5 years older than recipient (Older), donors within 5 years of recipient age (Equal Age), and donors >5 years younger than recipient (Younger, reference group). Cox multivariable analysis was performed to evaluate the effect of donor-recipient age difference on early and late graft survival. ResultsA total of 1,275 ACHD patients underwent HT (60% male, median 35 years-old (interquartile range 24-46) with median graft survival of 13.7 years (95% confidence interval [CI] 11.7-16.0). Compared to Younger donors (n=306 [24%]), graft survival was similar with Equal Age donors (n=698 [55%]; Log rank p=0.61), though significantly reduced with Older donors (n=271 [21%]; Log rank p=0.03). In multivariable analysis, late graft survival was similar with Equal Age donors but lower with Older donors (adjusted hazard ratio [aHR] 1.63, 95% CI 1.16-2.28, p=0.005), with a trend of reduced survival with Older donors in recipients <30 or ≥40 years-old. ConclusionsGraft survival in ACHD patients undergoing HT was similar for those with Younger and Equal Age donors. Recipients with Older donors had reduced 10-year survival, possibly related to increased risk in those <30 and ≥40 years-old. These data help inform optimal donor age for ACHD patients requiring HT.

Association of donor hepatectomy time with liver transplantation outcomes: A multicenter retrospective study.

Prolonged donor hepatectomy time may be implicated in early and late complications of liver transplantation. To evaluate the impact of donor hepatectomy time on outcomes of liver transplant recipients, mainly early allograft dysfunction. This multicenter retrospective study included brain-dead donors and adult liver graft recipients. Donor-recipient matching was obtained through a crossover list. Clinical and laboratory data were recorded for both donors and recipients. Donor hepatectomy, cold ischemia, and warm ischemia times were recorded. Primary outcome was early allograft dysfunction. Secondary outcomes included need for retransplantation, length of intensive care unit and hospital stay, and patient and graft survival at 12 months. From January 2019 to December 2021, a total of 243 patients underwent a liver transplant from a brain-dead donor. Of these, 57 (25%) developed early allograft dysfunction. The median donor hepatectomy time was 29 (23-40) min. Patients with early allograft dysfunction had a median hepatectomy time of 25 (22-38) min, whereas those without it had a median time of 30 (24-40) min (P = 0.126). Donor hepatectomy time was not associated with early allograft dysfunction, graft survival, or patient survival following liver transplantation.

A Drug Safety Briefing (II) in Transplantation from Real-World Individual Pharmacotherapy Management to Prevent Patient and Graft from Polypharmacy Risks at the Very Earliest Stage.

For early and long-term patient and graft survival, drug therapy in solid organ and hematopoietic stem cell transplantation inevitably involves polypharmacy in patients with widely varying and even abruptly changing conditions. In this second part, relevant medication briefing is provided, in addition to the scores defined in the previously published first part on the design of the Individual Pharmacotherapy Management (IPM). The focus is on the growing spectrum of contemporary polypharmacy in transplant patients, including early and long-term follow-up medications. 1. Unlike the available drug-drug interaction (DDI) tables, for the first time, this methodological all-in-one device refers to the entire risks, including contraindications, special warnings, adverse drug reactions (ADRs), and DDIs. The selection of 65 common critical drugs results from 10 years of daily IPM with real-world evidence from more than 60,800 IPM inpatient and outpatient medication analyses. It includes immunosuppressants and typical critical antimicrobials, analgesics, antihypertensives, oral anticoagulants, antiarrhythmics, antilipids, antidepressants, antipsychotics, antipropulsives, antiemetics, propulsives, proton pump inhibitors (PPIs), sedatives, antineoplastics, and protein kinase inhibitors. As a guide for the attending physician, the drug-related risks are presented in an alphabetical overview based on the Summaries of Product Characteristics (SmPCs) and the literature. 2. Further briefing refers to own proven clinical measures to manage unavoidable drug-related high-risk situations. Drug-induced injuries to the vulnerable graft and the immunosuppressed comorbid patient require such standardized, intensive IPM and the comprehensive preventive briefing toolset to optimize the outcomes in the polypharmacy setting.

Preoperative aortic regurgitation and early graft survival in liver transplant recipients

Preoperative aortic regurgitation and early graft survival in liver transplant recipients

Effect of donor resuscitation on early liver graft survival in donation after brain death

Effect of donor resuscitation on early liver graft survival in donation after brain death

TLR4 signalling in ischemia/reperfusion injury: a promising target for linking inflammation, oxidative stress and programmed cell death to improve organ transplantation outcomes.

Transplantations represent the principal therapeutic interventions for terminal organ failure, a procedure that has salvaged myriad lives annually. Ischemia/reperfusion injury (IRI) is frequently correlated with an unfavourable prognosis and is relevant for early graft dysfunction and graft survival. IRI constitutes a complex pathological state influenced by a series of factors such as oxidative stress, metabolic stress, leukocytic infiltration, programmed cell death pathways, and inflammatory immune responses. Reducing ischemia/reperfusion injury is one of the main directions of transplantation research. Toll-like receptors (TLRs) are important pattern-recognition receptors expressed on various organs that orchestrate the immune responses upon recognising PAMPs and DAMPs. Targeting the TLR4 signalling has recently been suggested as a promising approach for alleviating IRI by affecting inflammation, oxidative stress and programmed cell death (PCD). In this minireview, we summarise the role of TLR4 signalling in regulating inflammation, oxidative stress and PCD in organ transplantation and discuss their interactions during IRI. A detailed understanding of the multiple functions of TLR4 in IRI provides novel insights into developing therapies to improve organ transplantation outcomes.

Center Volume Predicts Improved Early Outcomes in Multiorgan Heart Transplantation

Center volume is associated with improved survival after isolated heart transplant, but its impact on multiorgan heart transplant (MHT) outcomes is unknown. This study examines the impact of institutional MHT volume on MHT outcomes. Adult patients undergoing first time MHT from 2011 to 2021 were identified in the United Network for Organ Sharing database. Transplant centers were annually classified as low-, medium-, or high-volume if they performed <3, 3 to 5, or ≥6 MHTs that year, respectively. Graft failure was defined as death, failure, or re-transplantation of any allograft. A total of 1860 MHTs were performed at 104 centers, including 482 (26%) at low-, 601 (32%) at medium-, and 777 (42%) at high-MHT volume centers. Noncardiac allografts included kidney (83%), liver (16%), and lung (2%). The proportion of MHTs performed at high-volume centers increased from 10% in 2011 to 62% in 2021. Recipient age, race, and body mass index did not vary by center volume (all P > .05). Patients at high-volume centers were more likely to be in the intensive care unit pre-transplant (58% vs 44%, P < .001) and have shorter waitlist times (47 vs 92 days, P < .001) than those at low-volume centers. 30-day graft survival was higher in combined medium- and high-volume compared with low-volume centers (95% vs 92%, P = .004). Increasing center MHT volume was protective against 30-day graft failure (adjusted hazard ratio 0.93 [0.88-0.98]) on multivariate Cox regression. Higher MHT volume is associated with improved early graft survival after MHT, which may justify centralizing the performance of MHTs to high-volume centers.

#6888 COMPARISON OF COMBINATION OF RITUXIMAB WITH LOW DOSE THYMOGLOBULIN VERSUS LOW DOSE THYMOGLOBULIN ALONE AS INDUCTION AGENT IN RENAL TRANSPLANTATION

Abstract Background and Aims Current immunosuppressive therapies and protocols have led to significant improvements in early patient and graft survival rates following kidney transplantation. However full dose rATG induction therapy (7-10 mg/kg) has been associated with increased morbidity. There is not much data available on the use of single dose low dose rATG and rituximab, a Anti CD 20 chimeric antibody in low sensitized Indian transplant recipients. To compare the efficacy of low dose single dose rATG(1–1.2mg/kg) versus combination of rituximab with low dose single dose rATG in ABO compatible low sensitization renal transplant recipients. Method Retrospective analysis of all renal transplant recipients between 2010 and 2022 in our center who received low dose rATG(1-1.2mg/kg) or a combination of single dose rituximab(375mg/m2) and low dose thymoglobulin were studied. Demographic data, donor characterstics, HLA matches, infections,rejections was collected Graft function at 3,6 and 12 months post transplant if available was collected. Data was analysed using SPSS 16. Results Of 86 patients studied, 58(67.4%) received single dose of low dose rATG(1-1.2 mg/kg/day) (Grp1) and 28 received a combination of single low dose rATG &amp; Rituximab(375mg/m2)(Grp 2)(32.5%). There was no significant difference between the Grp 1 and Grp 2 in terms of age,gender,vintage of dialysis, PRA status prior to transplant, no of HLA Matches, donor age and Donor GFR. There were 9(15%) of Acute cellular rejections (ACR) in Group1 when compared to 8 (28%) in-group 2(p = 0.263). The number of steroid resistant ACR were 2 (3%)in Grp 1 when compared to 3 (10%)in grp 2(p = 0.365) The number of ABMR were 5(8.6%) in group 1 when compared to 1(3.5%)in grp 2(p = 0.658) 15.5% had graft loss by 1 year in group 1 compared to none in grp 2(p = 0.322)CMV and BKV infections were seen in 1 and no pts and 1 patient in each group respectively.Overall infection rate was 24% when compared to 46.4% in grp 2(p = 0.03). The mean egfr(ml/min/1.73m2) at the end of 3 months, 6 months and 1 year was &amp;95.6,93,95 respectively in grp 1 when compared to 92, 89.4 &amp; 84.3 in grp 2. Conclusion The % of steroid resistant ACR and the number of infections were higher in the 1 year in the Single low dose rATG+Rituximab induction when compared to low single dose rATG alone. However ABMR was lower in the combination grp. Further prospective RCT s are required to establish the role of Rituximab in ABO Compatible transplants.

Analysis of Short-Term and Long-Term Outcomes of Living Donor Liver Transplantation for Patients with a High Model for End-Stage Liver Disease Score

The Model of End-Stage Liver Disease (MELD) scoring system can predict short-term survival among patients awaiting liver transplantation and is used to allocate organs prioritizing liver transplantation. Patients with high MELD scores have been reported to have worse early graft dysfunction and survival. However, recent studies have shown that patients with high MELD scores had satisfactory graft survival, although they showed more postoperative complications. In this study, we examined the effect of the MELD score on the short-term and long-term prognosis of living donor liver transplantation (LDLT). This study included 102 patients who underwent LDLT in our institution between 2005 and 2020. The patients were divided into 3 groups according to MELD score (low MELD group: ≤20, moderate MELD group: 21-30, and high MELD group: ≥31). Perioperative factors were compared among the 3 groups, and cumulative overall survival rates were calculated using the Kaplan-Meier method. The patients' characteristics were comparable, and the median age was 54 years. Hepatitis C virus cirrhosis was the most common primary disease (n=40), followed by hepatitis B virus (n=11). The low MELD group consisted of 68 patients (median score: 16, 10-20); the moderate MELD group, 24 patients (median score: 24, 21-30); and the high MELD group, 10 patients (median score: 35, 31-40). The mean operative time (1241 min versus 1278 min versus 1158 min, P=.19) and mean blood loss (7517 mL vs 11162 mL vs 8808 mL, P=.71) were not significantly different among the 3 groups. The vascular and biliary complication rates were similar. The periods of intensive care unit and hospital stay tended to be longer in the high MELD group, but the difference was insignificant. The 1-year postoperative survival rate (85.3 % vs 87.5 % vs 90.0 %, P=.90) and overall survival rate were also not significantly different among the 3 groups. Our study showed that LDLT patients with high MELD scores do not have a worse prognosis than those with low scores.

IL-18BP Improves Early Graft Function and Survival in Lewis-Brown Norway Rat Orthotopic Liver Transplantation Model.

Interleukin-18 (IL-18) can effectively activate natural killer (NK) cells and induce large concentrations of interferon-γ (IFN-γ). In healthy humans, IL-18 binding protein (IL-18BP) can inhibit the binding of IL-18 to IL-18R and counteract the biological action of IL-18 due to its high concentration and high affinity, thus preventing the production of IFN-γ and inhibiting NK-cell activation. Through previous studies and the phenomena observed by our group in pig-non-human primates (NHPs) liver transplantation experiments, we proposed that the imbalance in IL-18/IL-18BP expression upon transplantation encourages the activation, proliferation, and cytotoxic effects of NK cells, ultimately causing acute vascular rejection of the graft. In this research, we used Lewis-Brown Norway rat orthotopic liver transplantation (OLTx) as a model of acute vascular rejection. AAV8-Il18bp viral vectors as gene delivery vehicles were constructed for gene therapy to overexpress IL-18BP and alleviate NK-cell rejection of the graft after transplantation. The results showed that livers overexpressing IL-18BP had reduced damage and could function longer after transplantation, effectively improving the survival time of the recipients.

Expanding Criteria in Controlled Cardiac Death Donors: Now With 70-Year-Old Donors

Outcomes of kidney transplant (KT) after controlled cardiac death with older donors are under review. We aimed to analyze early and midterm clinical outcomes using older (≥70 years) controlled cardiac death donors (cDCD). Retrospective observational single-center study including all KTs from donors ≥70 years from cDCD and donors after brain death (DBD) performed from January 2017 to January 2022. We performed a comparative study between the 2 groups (cDCD and DBD). An analysis of clinical characteristics, early clinical outcomes, and patient and graft survival rates was made. We included 25 cDCD KTs and 63 DBD KTs ≥70 years. The median follow-up was 18.7 months. Recipients from cDCD were more comorbid. Donors from DBD showed higher hypertension and stroke rate. The KTs from older cDCD showed similar delayed graft function rate (cDCD: 34.6% vs DBD extended criteria donor: 35.3%, P=.59) and primary nonfunction (cDCD 16% vs DBD 17.4%, P=.85) compared with older DBD. Medium (3 years) graft death-censored survival was satisfying (cDCD 73% vs DBD 72%) despite a relevant early graft failure rate in both groups (cDCD 16% vs DBD 23%, P=.26). No differences were observed in patient survival at year 1 (cDCD 94% vs DBD 93%, P=.62). In our series, the outcomes with older cDCD are similar compared with older DBD. Although older donors showed an increase of early graft failure, these kidneys allowed us to maximize the opportunities for candidates that otherwise should remain on dialysis.

Kidney Transplantation Outcomes From Donors After Controlled Circulatory Death: A Comparison With Expanded Criteria Brain Death Donors

The persistent shortage of optimal kidney donors and the progressive increase in patients on the waiting list have led to an expansion of the acceptance criteria, such as donors after controlled cardiac death (cDCD) and donors after brain death with expanded criteria (DBD-EC). Some concerns and doubts about survival outcomes achieved with these allografts are still present. Our aim was to compare transplant outcomes from cDCD vs DBD-EC. A retrospective single-center observational study including all kidney transplant (KT) donors from all cDCD and DBD-EC (>60 years) from January 2015 to January 2022 was performed. We analyzed clinical characteristics, early clinical outcomes, and patient and graft survival rates. 129 cDCD and 166 DBD-EC KT recipients were included. The median follow-up was 30,2 months. DBD-EC were older and had more comorbidities than cDCD. KTs from cDCD and DBD-EC showed similar rates of delayed graft function and primary nonfunction. Patient survival at 1 year was similar (85% DBD-EC vs 90% cDCD, P=.32). Death-censored graft survival at 1 year was similar among young cDCD (18-59 years) and elderly DBD (60-69 years; 97% vs 92.3%, P=.2). Recipient age and expanded criteria in KT from cDCD were related to worse early graft outcomes. The outcomes achieved with KT from cDCD were similar to those observed in older and more comorbid DBD donors. This assumption is worth consideration when choosing the most suitable donor for each recipient.

Outcome of pediatric-to-adult liver transplantation:a single-center study in China

Objective: To explore the outcome of the pediatric-to-adult liver transplantation, including postoperative complications and relevant factors which affecting graft survival. Methods: Data of 55 patients undergoing pediatric-to-adult liver transplantation at the First Affiliated Hospital of Zhejiang University between January 2015 and August 2021 were retrospectively analyzed. The donors consisted of 34 males and 21 females, and the age was (11.8±4.7) years (range: 1 to 17 years). Among the cases,17 cases (30.9%) were donation of brain death,32 cases (58.2%) were donation of cardiac death, and 6 cases (10.9%) were donation after brain death plus cardiac death. The recipients consisted of 32 males and 23 females, and the age was (51.6±10.1) years (range: 27 to 70 years). Among the recipients,10 cases (18.2%) were ABO-incompatible liver transplantation.The influencing factors of early graft survival were analyzed by Student t test,Mann-Whitney U test or χ2 test,respectively.Survival curve was drawn by Kaplan-Meier method.Logistic multivariate analysis was used to analyze the independent relevant factors of early postoperative graft loss. Results: Up to October 31,2021,the follow-up time (M(IQR)) was 36.0(43.1)months(range:5.9 to 81.7 months).There were 13 cases with graft loss (two of them underwent re-transplantation due to acute liver failure).The monofactor analysis indicated that cold ischemia time and donor-recipient blood group matching were the relevant factors affecting the early graft survival rate(both P<0.05).Logistic multivariate analysis showed that cold ischemia time and history of recipient gastrointestinal bleeding were independent relevant factors(both P<0.05).Postoperative hepatic artery thrombosis occurred in 3 cases(5.5%), portal vein thrombosis diagnosed in 4 cases(7.3%), portal vein stenosis occurred in 2 cases(3.6%),biliary complications diagnosed in 7 cases(12.7%), and small liver syndrome was found in 8 cases(14.5%). Conclusions: Adult liver transplantation with pediatric donor liver is an effective method to treat end-stage liver disease.Cold ischemia time and history of recipient gastrointestinal bleeding were independent relevant factors for the early graft survival.

A Potential Route to Reduce Ischemia/Reperfusion Injury in Organ Preservation.

The pathophysiological process of ischemia and reperfusion injury (IRI), an inevitable step in organ transplantation, causes important biochemical and structural changes that can result in serious organ damage. IRI is relevant for early graft dysfunction and graft survival. Today, in a global context of organ shortages, most organs come from extended criteria donors (ECDs), which are more sensitive to IRI. The main objective of organ preservation solutions is to protect against IRI through the application of specific, nonphysiological components, under conditions of no blood or oxygen, and then under conditions of metabolic reduction by hypothermia. The composition of hypothermic solutions includes osmotic and oncotic buffering components, and they are intracellular (rich in potassium) or extracellular (rich in sodium). However, above all, they all contain the same type of components intended to protect against IRI, such as glutathione, adenosine and allopurinol. These components have not changed for more than 30 years, even though our knowledge of IRI, and much of the relevant literature, questions their stability or efficacy. In addition, several pharmacological molecules have been the subjects of preclinical studies to optimize this protection. Among them, trimetazidine, tacrolimus and carvedilol have shown the most benefits. In fact, these drugs are already in clinical use, and it is a question of repositioning them for this novel use, without additional risk. This new strategy of including them would allow us to shift from cold storage solutions to cold preservation solutions including multitarget pharmacological components, offering protection against IRI and thus protecting today’s more vulnerable organs.

The liver transplant surgeon Mondays blues: an Italian perspective

Poor data exist on the influence of holidays and weekdays on the number and the results of liver transplantation (LT) in Italy. The study’s main objective is to investigate the impact of holidays and the different days of the week on the LT number and early graft survival rates in a multi-centric Italian series. We performed a retrospective analysis on 1,026 adult patients undergoing first deceased-donor transplantation between January 2004 and December 2018 in the three university centers in Rome. During the 4,504 workdays, 881 LTs were performed (85.9%; one every 5.1 days on average). On the opposite, 145 LTs were done during the 975 holidays (14.1%; one every 7.1 days on average). Fewer LTs were performed on holidays (P = 0.004). There were no substantial differences in donor-, recipient- and transplant-related characteristics in LTs performed on weekdays or holidays. On Monday, fewer transplants were performed (vs. other weekdays: P < 0.0001; vs. Sunday: P = 0.03). At multivariable Cox regression analysis, LTs performed during the holiday or during the different days of the week were not found to be independent risk factors for the risk of 3- and 12-month graft loss. At three-month survival curves, no differences were observed among the transplants performed during the holidays versus the workdays (86.2 vs. 85.0%; P-0.70). The range of graft survival rates based on the day of the week was 81.6–86.9%, without showing any significant differences (P = 0.57). Fewer transplants are performed on holidays and Mondays. Survivals are not affected by holidays or the day the transplant is performed.

A randomized controlled trial to evaluate efficacy and safety of early conversion to a low-dose calcineurin inhibitor combined with sirolimus in renal transplant patients.

Background:The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods:Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/ cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion:The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration:Chinese Clinical Trial Registry, ChiCTR1800017277.

Analysis of Volatile Anesthetic-Induced Organ Protection in Simultaneous Pancreas-Kidney Transplantation.

Background: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia–reperfusion injury (IRI)—Remains a common cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients. Methods: Medical data of 105 patients undergoing SPKT between 1998–2018 were retrospectively analyzed and stratified according to the used VAs. The primary study endpoint was the association and effect of VAs on pancreas allograft failure following SPKT; secondary endpoint analyses included “IRI- associated posttransplant clinical outcome” as well as long-term graft function and outcome. Additionally, peak serum levels of C-reactive protein (CRP) and lipase during the first 72 h after SPKT were determined and used as further markers for “pancreatic IRI” and graft injury. Typical clinicopathological characteristics and postoperative outcomes such as early graft outcome and long-term function were analyzed. Results: Of the 105 included patients in this study three VAs were used: isoflurane (n = 58 patients; 55%), sevoflurane (n = 22 patients; 21%), and desflurane (n = 25 patients, 24%). Donor and recipient characteristics were comparable between both groups. Early graft loss within 3 months (24% versus 5% versus 8%, p = 0.04) as well as IRI-associated postoperative clinical complications (pancreatitis: 21% versus 5% versus 5%, p = 0.04; vascular thrombosis: 13% versus 0% versus 5%; p = 0.09) occurred more frequently in the Isoflurane group compared with the sevoflurane and desflurane groups. Anesthesia with sevoflurane resulted in the lowest serum peak levels of lipase and CRP during the first 3 days after transplantation, followed by desflurane and isoflurane (p = 0.039 and p = 0.001, respectively). There was no difference with regard to 10-year pancreas graft survival as well as endocrine/metabolic function among all three VA groups. Multivariate analysis revealed the choice of VAs as an independent prognostic factor for graft failure three months after SPKT (HR 0.38, 95%CI: 0.17–0.84; p = 0.029). Conclusions: In our study, sevoflurane and desflurane were associated with significantly increased early graft survival as well as decreased IRI-associated post-transplant clinical outcomes when compared with the isoflurane group and should be the focus of future clinical studies evaluating the positive effects of different VA agents in patients receiving SPKT.

The Utility of Early Allograft Dysfunction Components in Determining 90-Day Liver Graft Survival

Early allograft dysfunction (EAD) had been established as a useful tool to asses graft and patient survival after liver transplant. We wanted to evaluate effect of EAD components on early graft survival. This retrospective study included 264 patients with EAD after liver transplant in the period between 2015 and 2019. The patients with retransplants were excluded from analyses. The EAD was determined with Olthoff criteria. The logistic regression model was used for analyses. The 90-day graft survival was set as a primary outcome measure. The main indications for transplant in the analyzed group were hepatitis C virus infection (53 patients, 20.1%), hepatitis B infection (22, 8.3%), primary sclerosing cholangitis (28, 10.1%), and alcoholic liver disease (62, 23.5%), with a median model for end-stage liver disease score of 13.5 points. The 90-day graft loss occurred in 51 patients (19.3%). Each of the components used in EAD diagnosis was found to be correlated with 90-day graft loss. The bilirubin concentration on day 7 (odds ratio [OR], 3.1; 95% CI, 1.4-6.7; P < .001), international normalized ratio on day 7 (OR, 179; 95% CI, 39-815; P < .001), and the natural logarithm of alanine aminotransferase (OR, 3.1; 95% CI, 1.6-6.4) and aspartate aminotransferase (OR, 1.4; 95% CI, 0.4-4.9) predicted 90-day graft loss. In patients with EAD, international normalized ratio ≥ 1.6 on day 7 was the strongest predictor of early graft-loss among all EAD components.

Early Postoperative Transaminase Activities Affecting Early and Late Liver Graft Survival

This study aimed to examine the effect of transaminases' activities in the first posttransplant day on early (90-day) and late (5-year) graft survival. This retrospective cohort study included 612 patients after liver transplantation (LT) in the period between 2015 and 2019. Patients with acute liver failure and with vascular complications after LT were excluded. The natural logarithms of alanine transaminase (ALT) and aspartate transaminase (AST) were used for analyses using the logistic regression and Cox proportional hazards regression models. The optimal cut-off point for transaminases was determined using receiver operating characteristic curves. The 5-year graft survival was calculated after previously excluding the patients with 90-day graft loss. The ALT and AST were risk factors for 90-day graft loss (odds ratio 2.16; 95% CI 1.45-3.23; P < .001 and 2.23; 95% CI 1.55-3.19; P < .001, respectively). The optimal cut-off for ALT and AST in prediction of 90-day graft loss was ≥1030 and ≥3899 U/L; area under the curve 0.694 (95% CI 0.602-0.786; P < .001), with 11.3% and 97.1% positive predictive value (PPV) and negative predictive (NPV) value, and 0.673 (95% CI 0.575-0.772; P < .001), with 18.4% PPV and 95.6% NPV, respectively. The activities of AST and ALT on first posttransplant day were not identified as risk factors for late graft loss (P=.924 and P=.629, respectively). Early post-transplant transaminase activities can be used to determine early liver graft loss; however, their utility is lost for assessing the late graft survival.