Effects of early postnatal gastric and colonic microbiota transplantation on piglet gut health

Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut.To secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period.Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(CON,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and diversity.Results Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single housing.However,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to CON(all P<0.05).CcFT also showed a lower ETEC prevalence on d 27(P<0.05).CMT showed a higher alpha diversity and a difference in beta diversity compared to CON(P<0.05).Growth and other paraclinical endpoints were similar across groups.Conclusion In conclusion,only CcFT reduced ETEC-related post-weaning diarrhea.However,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration,longer treatment periods,and better donor quality should be explored by future research to optimize the protective effects of transplantation.

Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.

A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients.Unfortunately,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD.Herein,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages.Comparison of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))neutrophils.Moreover,we verified this immune niche and its association with EAD occurrence in two independent cohorts.Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.

Outcomes of early hospital readmission after kidney transplantation: Perspectives from a Canadian transplant centre

BACKGROUND Early hospital readmissions(EHRs)after kidney transplantation range in incidence from 18%-47%and are important and substantial healthcare quality indicators.EHR can adversely impact clinical outcomes such as graft function and patient mortality as well as healthcare costs.EHRs have been extensively studied in American healthcare systems,but these associations have not been explored within a Canadian setting.Due to significant differences in the delivery of healthcare and patient outcomes,results from American studies cannot be readily applicable to Canadian populations.A better understanding of EHR can facilitate improved discharge planning and long-term outpatient management post kidney transplant.AIM To explore the burden of EHR on kidney transplant recipients(KTRs)and the Canadian healthcare system in a large transplant centre.METHODS This single centre cohort study included 1564 KTRs recruited from January 1,2009 to December 31,2017,with a 1-year follow-up.We defined EHR as hospitalizations within 30 d or 90 d of transplant discharge,excluding elective procedures.Multivariable Cox and linear regression models were used to examine EHR,late hospital readmissions(defined as hospitalizations within 31-365 d for 30-d EHR and within 91-365 d for 90-d EHR),and outcomes including graft function and patient mortality.RESULTS In this study,307(22.4%)and 394(29.6%)KTRs had 30-d and 90-d EHRs,respectively.Factors such as having previous cases of rejection,being transplanted in more recent years,having a longer duration of dialysis pretransplant,and having an expanded criteria donor were associated with EHR post-transplant.The cumulative probability of death censored graft failure,as well as total graft failure,was higher among the 90-d EHR group as compared to patients with no EHR.While multivariable models found no significant association between EHR and patient mortality,patients with EHR were at an increased risk of late hospital readmissions,poorer kidney function throughout the 1st year post-transplant,and higher hospital-based care costs within the 1st year of follow-up.CONCLUSION EHRs are associated with suboptimal outcomes after kidney transplant and increased financial burden on the healthcare system.The results warrant the need for effective strategies to reduce post-transplant EHR.

Prognostic implication of early posttransplant hypercholesterolemia in liver transplantation for patients with hepatocellular carcinoma

Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. Results: Early posttransplant hypercholesterolemia(EPHC) was independently inversely associated with the risk of recurrence [hazard ratio(HR) = 0.630;P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC(B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence(HR = 0.504;P = 0.006) and mortality(HR = 0.511;P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival(89.6% and 83.7% vs. 83.8% and 72.7% respectively;P = 0.023), and 1-year and 3-year overall survival(95.8% and 84.8% vs. 94.6% and 77.6% respectively;P = 0.039). In the subgroup analysis, BEPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria;whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC(recurrence HR = 0.306, P = 0.011;mortality HR = 0.325, P = 0.031).Conclusions: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.

Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation

BACKGROUND Clinical factors predicting graft survival(GS)after ABO-incompatible(ABOi)liver transplantation(LT),and differences between recipients with and without hepatocellular carcinoma(HCC)are unclear.AIM To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without(HCC)in ABOi living-donor liver transplantation(LDLT).METHODS We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT,including 47 patients with HCC.RESULTS The 1-,3-,5-,and 10-year GS rates were 85.9%,73.3%,71.4%,and 71.4%,respectively,and there were no significant differences between HCC and non-HCC recipients.In multivariate Coxregression analyses,tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT,in addition to the antibody-mediated rejection(AMR)were associated with poor-graft outcomes.In HCC patients,AMR[hazard ratio(HR)=63.20,P<0.01]and HCC recurrence(HR=20.72,P=0.01)were significantly associated with poor graft outcomes.HCCs outside Milan criteria,and tacrolimus concentrations at 4 wk post-LT>7.3 ng/mL were significant predictive factors for HCC recurrence.After propensity score matching,patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free survival.CONCLUSION Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC recurrence.Therefore,careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.

Inferior outcomes of liver transplantation for hepatocellular carcinoma during early-COVID-19 pandemic in the United States

BACKGROUND Early in the coronavirus disease 2019(COVID-19)pandemic,there was a significant impact on routine medical care in the United States,including in fields of transplantation and oncology.AIM To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation(LT)for hepatocellular carcinoma(HCC)in the United States.METHODS WHO declared COVID-19 as a pandemic on March 11,2020.We retrospectively analyzed data from the United Network for Organ Sharing(UNOS)database regarding adult LT with confirmed HCC on explant in 2019 and 2020.We defined pre-COVID period from March 11 to September 11,2019,and early-COVID period as from March 11 to September 11,2020.RESULTS Overall,23.5%fewer LT for HCC were performed during the COVID period(518 vs 675,P<0.05).This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July 2020.Among LT recipients for HCC,concurrent diagnosis of non-alcoholic steatohepatitis significantly increased(23 vs 16%)and alcoholic liver disease(ALD)significantly decreased(18 vs 22%)during the COVID period.Recipient age,gender,BMI,and MELD score were statistically similar between two groups,while waiting list time decreased during the COVID period(279 days vs 300 days,P=0.041).Among pathological characteristics of HCC,vascular invasion was more prominent during COVID period(P<0.01),while other features were the same.While the donor age and other characteristics remained same,the distance between donor and recipient hospitals was significantly increased(P<0.01)and donor risk index was significantly higher(1.68 vs 1.59,P<0.01)during COVID period.Among outcomes,90-day overall and graft survival were the same,but 180-day overall and graft were significantly inferior during COVID period(94.7 vs 97.0%,P=0.048).On multivariable Coxhazard regression analysis,COVID period emerged as a significant risk factor of post-transplant mortality(Hazard ratio 1.85;95%CI:1.28-2.68,P=0.001).CONCLUSION During COVID period,there was a significant decrease in LTs performed for HCC.While early postoperative outcomes of LT for HCC were same,the overall and graft survival of LTs for HCC after 180 days were significantly inferior.

Symptomatic Val122del mutated hereditary transthyretin amyloidosis: Need for early diagnosis and prioritization for heart and liver transplantation

Background: Hereditary transthyretin(ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils(i.e. amyloid). Apart from the common Val30 Met mutation there is a very heterogeneous group of non-Val30 Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy. Methods: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122 del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed. Results: Three patients needed a staged(1 patient) or simultaneous(2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac(allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months. Conclusions: This is the first report in(liver) transplant literature about the rare Val122 del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.

Influence of Transplantation in Different Stage on Growth and Yield of Spring Maize in Shanxi Early Mature Area

In order to explore a new mulch-free maize planting mode and the best seedling age for maize transplantation in Shanxi early mature area,a field experiment was carried out using completely randomized block design.Taking mulch-based direct sowing as the control group,effects of transplantation in different stage on maize growing process,plant height,three-ear leaf area in mature period,and yield and composition factors of maize were studied.Results indicate that growing process of maize seedlings transplanted in every stage is slightly slower than the control group.Transplantation has effect of reducing plant height and three-ear leaf area in mature period.There was no significant difference between the yield of maize transplanted on May 1st and the control group,and the yield declined only by 7% compared with mulch-based direct sowing(CK).Damages to maize seedlings by the local late frost must be noticed when maize is planted by the method of mulch-free transplantation in early mature area.Transplanting the seedlings earlier after the late frost is deemed as an appropriate period in this area.

Risk factors associated with early and late HAT after adult liver transplantation

AIM: To identify risk factors that might contribute to hepatic artery thrombosis (HAT) after liver transplantation (LT). METHODS: The perioperative and follow-up data of a total of 744 liver transplants, performed from February 1999 to July 2010, were retrospectively reviewed. HAT developed in 20 patients (2.7%). HAT was classified as early (occurring in fewer than 30 d post LT) or late (occurring more than 30 d post LT). Early HAT devel-oped in 14 patients (1.9%). Late HAT developed in 6 patients (0.8%). Risk factors associated with HAT were analysed using the chi(2) test for univariate analysis and logistic regression for multivariate analysis. RESULTS: Lack of ABO compatibility, recipient/donor weight ratio >= 1.15, complex arterial reconstruction, duration time of hepatic artery anastomosis > 80 min, duration time of operation > 10 h, dual grafts, number of units of blood received intraoperatively >= 7, number of units of fresh frozen plasma (FFP) received intraoperatively >= 6, postoperative blood transfusion and postoperative FFP use were significantly associated with early HAT in the univariate analysis (P < 0.1). After logistic regression, independent risk factors associated with early HAT were recipient/donor weight ratio >= 1.15 (OR = 4.499), duration of hepatic artery anastomosis > 80 min (OR = 5.429), number of units of blood received intraoperatively >= 7 (OR = 4.059) and postoperative blood transfusion (OR = 6.898). Graft type (whole/living-donor/split), duration of operation > 10 h, retransplantation, rejection reaction, recipients with diabetes preoperatively and recipients with a high level of blood glucose or diabetes postoperatively were significantly associated with late HAT in the univariate analysis (P < 0.1). After logistic regression, the independent risk factors associated with early HAT were duration of operation > 10 h (OR = 6.394), retransplantation (OR = 21.793) and rejection reactions (OR = 16.936). CONCLUSION: Early detection of these risk factors, strict surveillance protocols by Doppler ultrasound and prophylactic anticoagulation for recipients at risk might be determined prospectively. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Effect of perioperative fluid therapy on early phase prognosis after liver transplantation

BACKGROUND: Although liver transplantation (LT) has made rapid progress, early pulmonary complications still occur. More attention should be paid to fluid therapy that may be an important factor leading to these complications. It is necessary to investigate the correlation between intraoperative and postoperative fluid therapy and early pulmonary complications after LT, then attempt to provide a reasonable fluid therapy in the perioperative period. METHODS: Sixty-two patients who had undergone Ff were enrolled and analyzed retrospectively. Based on early phase prognosis after LT, the 62 patients were divided into a non-pulmonary complication group and a pulmonary complication group. Twenty perioperative variables were analyzed in both groups to screen out several factors causing early pulmonary complications, then the parameters reflecting postoperative recovery were analyzed. RESULTS: The pulmonary complication group had 29 patients (46.77%), 3 (4.84%) of whom died during the perioperative period. Using monofactorial analysis for each variable, the two groups differed in the following variables: preoperative lung function, volume of intraoperative transfusion, volume of intraoperative bleeding, and volume of intraoperative net fluid retention and fluid balance (<=-500 ml) in >= 2 of the first 3 days after operation. Analysis of the relationship between multivariate factors and pulmonary complications after LT by logistic multivariate regression analysis showed that preoperative lung function, volume of intraoperative bleeding, and fluid balance (<=-500 ml) in >=-2 of the first 3 days after operation were influential factors. CONCLUSIONS: It is important to maintain fluid balance during the perioperative period of LT. If the hemodynamics are stable, appropriate negative fluid balance in the first 3 days after operation apparently decreases the incidence of early pulmonary complications after LT. These measures are associated with better postoperative recovery.

Comprehensive risk assessment for early neurologic complications after liver transplantation

AIM: To determine risk factors for early neurologic complications(NCs) after liver transplantation from perspective of recipient, donor, and surgeon. METHODS: In all, 295 adult recipients were enrolled consecutively between August 2001 and February 2014 from a single medical center in Taiwan. Any NC in the first 30 d post-liver transplantation, and perioperative variables from multiple perspectives were collected and analyzed. The main outcome was a 30-d NC. Generalized additive models were used to detect the non-linear effect of continuous variables on outcome, and to determine cut-off values for categorizing risk. Risk factors were identified using multiple logistic regression analysis. RESULTS: In all, 288 recipients were included, of whom 142(49.3%) experienced at least one NC, with encephalopathy being the most common 106(73%). NCs prolonged hospital stay(35.15 ± 43.80 d vs 20.88 ± 13.58 d, P < 0.001). Liver recipients' age < 29 or ≥ 60 years, body mass index < 21.6 or >27.6 kg/m^2, Child-Pugh class C, history of preoperative hepatoencephalopathy or mental disorders, day 7 tacrolimus level > 8.9 ng/m L, and postoperative intraabdominal infection were more likely associated with NCs. Novel risk factors for NCs were donor age < 22 or ≥ 40 years, male-to-male gender matching, graftrecipient weight ratio 0.9%-1.9%, and sequence of transplantation between 31 and 174. CONCLUSION: NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation.

Noninvasive indocyanine green plasma disappearance rate predicts early complications,graft failure or death after liver transplantation

BACKGROUND:Early detection of graft malfunction or postoperative complications is essential to save patients and organs after orthotopic liver transplantation (OLT).Predictive tests for graft dysfunction are needed to enable earlier implementation of organ-saving interventions following transplantation.This study was undertaken to assess the value of indocyanine green plasma disappearance rates (ICG-PDRs) for predicting postoperative complications,graft dysfunction and patient survival following OLT.METHODS:Eighty-six patients undergoing OLT were included in this single-centre trial.ICG-PDR was assessed daily for the first 7 days following OLT.Endpoints were graft loss or death within 30 days and postoperative complications,graft loss,or death within 30 days.RESULTS:Postoperative complications of 31 patients included deaths (12 patients) or graft losses.ICG-PDR was significantly different in patients whose endpoints were graft loss or death beginning from day 3 and in those whose endpoints were graft loss,death,or postoperative complications beginning from day 4 after OLT.For day 7 measurements,receiver operating characteristic curve analysis revealed an ICG-PDR cut-off for predicting death or graft loss of 9.6% per min (a sensitivity of 75.0%,a specificity of 72.6%,positive predictive value 0.35 negative predictive value 0.94).For prediction of graft loss,death or postoperative complications,the ICG-PDR cut-off was 12.3%per min (a sensitivity of 68.9%,a specificity of 66.7%,positive predictive value 0.57,negative predictive value 0.77).CONCLUSIONS:ICG-PDR measurements on postoperative day 7 are predictive of early patient outcomes following OLT.The added value over that of routinely determined laboratory parameters is low.

Prediction of early recurrence of hepatocellular carcinoma after liver transplantation based on computed tomography radiomics nomogram

Background:Early recurrence results in poor prognosis of patients with hepatocellular carcinoma(HCC)after liver transplantation(LT).This study aimed to explore the value of computed tomography(CT)-based radiomics nomogram in predicting early recurrence of patients with HCC after LT.Methods:A cohort of 151 patients with HCC who underwent LT between December 2013 and July 2019 were retrospectively enrolled.A total of 1218 features were extracted from enhanced CT images.The least absolute shrinkage and selection operator algorithm(LASSO)logistic regression was used for dimension reduction and radiomics signature building.The clinical model was constructed after the analysis of clin-ical factors,and the nomogram was constructed by introducing the radiomics signature into the clinical model.The predictive performance and clinical usefulness of the three models were evaluated using re-ceiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA),respectively.Cali-bration curves were plotted to assess the calibration of the nomogram.Results:There were significant differences in radiomics signature among early recurrence patients and non-early recurrence patients in the training cohort(P<0.001)and validation cohort(P<0.001).The nomogram showed the best predictive performance,with the largest area under the ROC curve in the training(0.882)and validation(0.917)cohorts.Hosmer-Lemeshow testing confirmed that the nomogram showed good calibration in the training(P=0.138)and validation(P=0.396)cohorts.DCA showed if the threshold probability is within 0.06-1,the nomogram had better clinical usefulness than the clinical model.Conclusions:Our CT-based radiomics nomogram can preoperatively predict the risk of early recurrence in patients with HCC after LT.

Clinical practice of early extubation after liver transplantation

BACKGROUND: Anesthetic practices such as early tracheal extubation facilitate postoperative recovery. Early extubation after liver transplantation has been adopted by some centers in the recent two decades. No universal clinical guidelines are used and questions remain. This review aimed to address the current status of early extubation after liver transplantation. DATA SOURCES: A literature search of MEDLINE and ISI Web of Knowledge databases was performed using terms such as liver transplantation, early extubation, immediate tracheal extubation fast tracking or fast track anesthesia and postoperative tracheal extubation. Additional papers were identified by a manual search of the references in the key articles. RESULTS: Review of the available literature provided an insight into the definition, evolution, advantages and risks of early extubation, and anesthetic techniques that prompt early extubation in liver transplant patients. Early extubation has proved to be feasible and safe in these patients, but the outcomes are still uncertain. CONCLUSIONS: Early extubation after liver transplantation is feasible, safe and cost-effective in the majority of patients and has been increasingly accepted as an option for conventional postoperative ventilation. Comprehensive and individualized evaluation of the patient’s condition before extubation by an experienced anesthesiologist is the cornerstone of success Understanding of its effect on the outcome remains incomplete In the future, additional trials are required to establish universal early extubation guidelines and to determine its benefits for patients and practitioners.

Expression of iNOS in early injury in a rat model of small-for-size liver transplantation

BACKGROUND: Living donor liver transplantation has been widely accepted as the treatment of choice for end-stage liver disease. Large amounts of nitric oxide generated by inducible nitric oxide synthase (iNOS) have been shown to play an important role in many inflammatory and immune reactions, but expression of iNOS in small-for-size liver transplantation is unknown. The aims of this study were to determine the time course of iNOS mRNA and protein as well as the redox state of liver biopsies in a rat model of small-for-size liver transplantation. METHODS: Male Sprague-Dawley rats were divided into a control group, a warm ischemia-reperfusion (IR) group, and a small-for-size liver graft group. Real-time RT-PCR and Western blotting were used to characterize the time course of the expression of iNOS mRNA and protein, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) were used as markers to characterize the redox state of liver tissues, and the time courses of MDA and SOD levels were also measured. RESULTS: The expression of iNOS mRNA and protein levels in the warm IR and small-for-size graft groups both significantly increased after reperfusion, and peaked at 3 hours. Moreover, the increase in MDA was accompanied by increased iNOS in the period of 1-24 hours after reperfusion. The MDA levels in the warm IR and small-for-size graft groups significantly increased after reperfusion, peaked at 3 hours, and decreased thereafter. The direction of change in SOD was opposite that of the change in MDA. CONCLUSIONS: The expression of iNOS mRNA and protein is activated after reperfusion both in hepatic warm IR injury and small-for-size liver graft. Furthermore, the results of this study suggest that iNOS contributes to the damage in warm IR injury and small-for-size grafts via free oxygen radicals.

Predicting early outcomes of liver transplantation in young children: The EARLY study

AIM To determine potentially modifiable predictors of early outcomes after liver transplantation in children of age < 3 years.METHODS This study was a retrospective chart review including all consecutive children of age less than 3-years-old having had a liver transplant done at the Western Canadian referral center from June 2005 to June 2015.Pre-specified potential predictor variables and primary and secondary outcomes were recorded using standard definitions and a case report form. Associations between potential predictor variables and outcomes were determined using univariate and multiple logistic [odds ratio(OR); 95%CI] or linear(effect size, ES; 95%CI) regressions. RESULTS There were 65 children, of mean age 11.9(SD 7.1) mo and weight 8.5(2.1) kg, with biliary-atresia in 40(62%), who had a living related donor [LRD; 29(45%)], split/reduced [21(32%)] or whole liver graft [15(23%)]. Outcomes after liver transplant included: ventilator-days of 12.5(14.1); pediatric intensive care unit mortality of 5(8%); re-operation in 33(51%), hepatic artery thrombosis(HAT) in 12(19%), portal vein thrombosis(PVT) in 11(17%), and any severe complication(HAT, PVT, bile leak, bowel perforation, intraabdominal infection, retransplant, or death) in 32(49%) patients. Predictors of the prespecified primary outcomes on multiple regression were:(1) HAT: split/reduced(OR 0.06; 0.01, 0.76; P = 0.030) or LRD(OR 0.16; 0.03, 0.95; P = 0.044) vs whole liver graft; and(2) ventilator-days: surgeon(P < 0.05), lowest antithrombin(AT) postoperative day 2-5(ES-0.24;-0.47,-0.02; P = 0.034), and split/reduced(ES-12.5;-21.8,-3.2; P = 0.009) vs whole-liver graft. Predictors of the pre-specified secondary outcomes on multiple regression were:(1) any thrombosis: LRD(OR 0.10; 0.01, 0.71; P = 0.021) or split/reduced(OR 0.10; 0.01, 0.85; P = 0.034) vs whole liver graft, and lowest AT postoperative day 2-5(OR 0.93; 0.87, 0.99; P = 0.038); and(2) any severe complication: surgeon(P < 0.05), lowest AT postoperative day 2-5(OR 0.92; 0.86-0.98; P = 0.016), and split/reduced(OR 0.06; 0.01, 0.78; P = 0.032) vs whole-liver graft. CONCLUSION In young children, whole liver graft and surgeon was associated with more complications, and higher AT postoperative day 2-5 was associated with fewer complications early after liver transplantation.

Preoperative hepatic hemodynamics in the prediction of early portal vein thrombosis after liver transplantation in pediatric patients with biliary atresia

BACKGROUND： Portal vein thrombosis （PVT） is one of the main vascular complications after liver transplantation （LT）, especially in pediatric patients with biliary atresia （BA）. This study aimed to assess the preoperative hepatic hemodynamics in pediatric patients with BA using Doppler ultrasound and determine whether ultrasonographic parameters may predict early PVT after LT.METHODS： One hundred and twenty-eight pediatric patients with BA younger than 3 years of age underwent Doppler ultra- sound within seven days before LT, between October 2006 and June 2013. The preoperative hepatic hemodynamic parameters were then compared between patients with early PVT （within 1 month following LT） and those without PVT. Receiver oper- ating characteristic analysis was performed to determine the optimal cutoff value for predicting early PVT. RESULTS： Of the 128 transplant recipients, 41 （32.03%） had a hypoplastic portal vein （PV）, 52 （40.63%） had hepatofugal PV flow and 40 （31.25%） had a high hepatic artery resistance index （HARI） of 〉1. Nine cases （7.03%） experienced early PVT. A PV diameter 〈4 mm （sensitivity 88.89%, specificity 72.27%）, and a hepatofugal PV flow （sensitivity 77.78%, specificity 62.18%） with a high HARI ≥1 （sensitivity 77.78%, specificity 72.27%） were hepatic hemodynamic risk factors for early PVT.（ CONCLUSIONS： Hepatic hemodynamic disturbances in pediatric recipients with BA were more common. Small PV diameter （≤4 mm） and hepatofugal PV flow combined with high HARI （≥1） are strong warning signs of early PVT after LT in pediatric patients with BA. Intense monitoring of vascular patency and prophylactic thrombolytic therapy should be considered in pediatric patients undergoing LT for BA.

Individualized peri-operative fluid therapy facilitating early-phase recovery after liver transplantation

AIM:To investigate the correlation between peri-operative fluid therapy and early-phase recovery after liver transplantation(LT) by retrospectively reviewing 102 consecutive recipients.METHODS:Based on whether or not the patients had pulmonary complications,the patients were categorized into non-pulmonary and pulmonary groups.Twentyeight peri-operative variables were analyzed in both groups to screen for the factors related to the occurrence of early pulmonary complications.RESULTS:The starting hemoglobin(Hb) value,an intra-operative transfusion > 100 mL/kg,and a fluid balance ≤-14 mL/kg on the first day and the second or third day post-operatively were significant factors for early pulmonary complications.The extubation time,time to initial passage of flatus,or intensive care unit length of stay were significantly prolonged in patients who had not received an intra-operative transfusion ≤ 100 mL/kg or a fluid balance ≤-14 mL/kg on the first day and the second or the third day post-operatively.Moreover,these patients had poorer results in arterial blood gas analysis.CONCLUSION:It is important to offer a precise and individualized fluid therapy during the peri-operative period to the patients undergoing LT for cirrhosis-associated hepatocellular carcinoma.

Intra-arterial thrombolysis for early hepatic artery thrombosis after liver transplantation

BACKGROUND Early hepatic artery thrombosis(E-HAT)is a serious complication after liver transplantation(LT),which often results in graft failure and can lead to patient deaths.Treatments such as re-transplantation and re-anastomosis are conventional therapeutic methods which are restricted by the shortage of donors and the patient’s postoperative intolerance to re-laparotomy.Due to the advances in interventional techniques and thrombolytics,endovascular treatments are increasingly being selected by more and more centers.This study reviews and reports our single-center experience with intra-arterial thrombolysis as the first choice therapy for E-HAT after deceased donor LT.AIM To evaluate the feasibility and reasonability of intra-arterial thrombolysis for EHAT after deceased donor LT.METHODS A total of 147 patients who underwent deceased donor LT were retrospectively reviewed in our hospital between September 2011 and December 2016.Four patients were diagnosed with E-HAT.All of these patients underwent intraarterial thrombolysis with alteplase as the first choice therapy after LT.The method of arterial anastomosis and details of the diagnosis and treatment of EHAT were collated.The long-term prognosis of E-HAT patients was also recorded.The median follow-up period was 26 mo(range:23 to 30 mo).RESULTS The incidence of E-HAT was 2.7%(4/147).E-HAT was considered when Doppler ultrasonography showed no blood flow signals and a definite diagnosis was confirmed by immediate hepatic arterial angiography when complete occlusion of the hepatic artery was observed.The patients were given temporary thrombolytics(mainly alteplase)via a 5-Fr catheter which was placed in the proximal part of the thrombosed hepatic artery followed by continuous alteplase using an infusion pump.Alteplase dose was adjusted according to activated clotting time.The recanalization rate of intra-arterial thrombolysis in our study was 100%(4/4)and no thrombolysis-related mortality was observed.During the follow-up period,patient survival rate was 75%(3/4),and biliary complications were present in 50%of patients(2/4).CONCLUSION Intra-arterial thrombolysis can be considered first-line treatment for E-HAT after deceased donor LT.Early diagnosis of E-HAT is important and follow-up is necessary even if recanalization is successful.