BACKGROUND: Primary graft dysfunction (PGD) causes complications in liver transplantation, which result in poor prognosis. Recipients who develop PGD usually experience a longer intensive care unit and hospital stay a...BACKGROUND: Primary graft dysfunction (PGD) causes complications in liver transplantation, which result in poor prognosis. Recipients who develop PGD usually experience a longer intensive care unit and hospital stay and have higher mortality and graft loss rates compared with those without graft dysfunction. However, because of the lack of universally accepted definition, early diagnosis of graft dysfunction is difficult. Additionally, numerous factors affect the allograft function after transplantation, making the prediction of PGD more difficult. The present review was to analyze the literature available on PGD and to propose a definition.DATA SOURCE: A search of PubMed (up to the end of 2012) for English-language articles relevant to PGD was performed to clarify the characteristics, risk factors, and possible treatments or interventions for PGD.RESULTS: There is no pathological diagnostic standard; many documented definitions of PGD are different. Many factors such as donor status, procurement and transplant process and recipient illness may affect the function of graft, and ischemia reperfusion injury is considered the direct cause. Potentia managements which are helpful to improve graft function were investigated. Some of them are promising.CONCLUSIONS: Our analyses suggested that the definition of PGD should include one or more of the following variables: (1)bilirubin ≥10 mg/dL on postoperative day 7; (2) internationa normalized ratio ≥1.6 on postoperative day 7; and (3) alanine aminotransferase or aspartate aminotransferase 】2000 IU/L within 7 postoperative days. Reducing risk factors may decrease the incidence of PGD. A majority of the recipients could recover from PGD; however, when the graft progresses intoprimary non-function, the patients need to be treated with retransplantation.展开更多
AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The whole experiment was divided into three groups: (1) Normal g...AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The whole experiment was divided into three groups: (1) Normal group (n = 12): normal BN rats without any drug or operation; (2) SGT group (syngeneic transplant of BN-BN, n = 12): both donors and recipients were BN rats; and (3) AGT group (allogeneic transplant of LEW-BN, n = 12): Donors were Lewis and recipients were BN rats. In the AGT group, all recipients were subcutaneously injected by Cyclosporin A after LT. Survival time was observed for 1 year. All the dying rats were sampled, biliary tract tissues were performed bacterial culture and liver tissues for histological study. Twenty-one d after LT, 8 rats were selected randomly in each group for sampling. Blood samples from caudal veins were collected for measurements of plasma endotoxin, cytokines and metabonomic analysis, and faeces were analyzed for intestinal microflora. RESULTS: During the surgery of LT, no complications of blood vessels or bile duct happened, and all rats in each group were still alive in the next 2 wk. The long term observation revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft diseases, 5 rats in which died of chronic bile duct hyperplasia. Compared to the SGT and normal groups, survival ratio of rats significantly decreased in the AGT group (aP < 0.01, bP < 0.001, respectively). Moreover, liver necrosis, liver infection, and severe chronic bile duct hyperplasia were observed in the AGT group by H and E stain. On 21 d after LT, compared with the normal group (25.38 ± 7.09 ng/L) and SGT group (33.12 ± 10.26 ng/L), plasma endotoxin in the AGT group was remarkably increased (142.86 ± 30.85 ng/L) (both P < 0.01). Plasma tumor necrosis factor-α and interleukin-6 were also significantly elevated in the AGT group (593.6 ± 171.67 pg/mL, 323.8 ± 68.30 pg/mL) vs the normal (225.5 ± 72.07 pg/mL, 114.6 ± 36.67 pg/mL) and SGT groups (321.3 ± 88.47 pg/mL, 205.2 ± 53.06 pg/mL) (P < 0.01). Furthermore, Bacterial cultures of bile duct tissues revealed that the rats close to death from the SGT and AGT groups were strongly positive, while those from the normal group were negative. The analysis of intestinal microflora was performed. Compared to the normal group (7.98 ± 0.92, 8.90 ± 1.44) and SGT group (8.51 ± 0.46, 9.43 ± 0.69), the numbers of Enterococcus and Enterobacteria in the AGT group (8.76 ± 1.93, 10.18 ± 1.64) were significantly increased (both aP < 0.01, bP < 0.05, respectively). Meanwhile, compared to the normal group (9.62 ± 1.60, 9.93 ± 1.10) and SGT group (8.95 ± 0.04, 9.02 ± 1.14), the numbers of Bifidobacterium and Lactobacillus in the AGT group (7.83 ± 0.72, 8.87± 0.13) were remarkably reduced (both aP < 0.01, bP < 0.05, respectively). In addition, metabonomics analysis showed that metabolic profiles of plasma in rats in the AGT group were severe deviated from the normal and SGT groups. CONCLUSION: Chronic bile duct hyperplasia is a pathological type of CGD following LT in rats. The mechanism of this kind of CGD is associated with the alterations of inflammation, intestinal barrier function and microflora as well as plasma metabolic profiles.展开更多
AIM:To describe a condition that we define as early graft dysfunction(EGD)which can be identified preoperatively. METHODS:Small-for-size graft dysfunction following living-related liver transplantation(LRLT)is charact...AIM:To describe a condition that we define as early graft dysfunction(EGD)which can be identified preoperatively. METHODS:Small-for-size graft dysfunction following living-related liver transplantation(LRLT)is characterized by EGD when the graft-to-recipient body weight ratio(GRBWR)is below 0.8%.However, patients transplanted with GRBWR above 0.8%can develop dysfunction of the graft.In 73 recipients of LRLT(GRBWR>0.8%),we identified 10 patients who developed EGD.The main measures of outcomes analyzed were overall mortality,number of re-transplants and length of stay in days(LOS).Furthermore we analyzed other clinical pre-transplant variables,intraoperative parameters and post transplant data.RESULTS:A trend in favor of the non-EGD group(3-mo actuarial survival 98%vs 88%,P=0.09;3-mo graft mortality 4.7%vs 20%,P=0.07)was observed as well as shorter LOS(13 d vs 41.5 d;P=0.001)and smaller requirement of peri-operative Units of Plasma (4 vs 14;P=0.036).Univariate analysis of pre- transplant variables identified platelet count,serum bilirubin,INR and Meld-Na score as predictors of EGD. In the multivariate analysis transplant Meld-Na score (P=0.025,OR:1.175)and pretransplant platelet count(P=0.043,OR:0.956)were independently associated with EGD. CONCLUSION:EGD can be identified preoperatively and is associated with increased morbidity after LRLT. A prompt recognition of EGD can trigger a timely treatment.展开更多
Lung transplantation is the treatment of choice for patients with end-stage lung disease.Currently,just under 5000 lung transplants are performed worldwide annually.However,a major scourge leading to 90-d and 1-year m...Lung transplantation is the treatment of choice for patients with end-stage lung disease.Currently,just under 5000 lung transplants are performed worldwide annually.However,a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction.It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant.This review aims to provide an in-depth analysis of the epidemiology,pathophysiology,risk factors,outcomes,and future frontiers involved in mitigating primary graft dysfunction.The current diagnostic criteria are examined alongside changes from the previous definition.We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion.Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality,ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.展开更多
BACKGROUNDThe impact of long-term dialysis (LTD) therapy on the survival benefit of kidneytransplantation compared to short-term dialysis (STD) remains unclear. Additionally,donor organ quality has been identified as ...BACKGROUNDThe impact of long-term dialysis (LTD) therapy on the survival benefit of kidneytransplantation compared to short-term dialysis (STD) remains unclear. Additionally,donor organ quality has been identified as a significant predictor ofpatient survival in deceased donor kidney transplantation.AIMTo investigate the effects of the best graft function within three months posttransplant,as well as dialysis duration, on transplant outcomes.METHODSA total of 255 patients were included in this retrospective cohort study. Patientswere divided into two groups: Those with LTD (≥ 15 years;Group LTD) and thosewith STD (< 15 years;Group STD). Clinical backgrounds and outcomes werecompared between the groups.RESULTSGroup LTD comprised 28 patients, while Group STD included 227 patients. Therewere no significant differences between the two groups in terms of age at transplant,donor age, lowest serum creatinine (best S-Cr) within three months posttransplant,or the frequency of cardiovascular events after transplantation. Multivariateanalysis identified age [hazard ratio (HR): 1.058;95%CI: 1.002-1.116;P =0.040], post-transplant incidence of cardiovascular disease (HR: 20.264;95%CI:6.052-67.850;P < 0.001), and best S-Cr (HR: 4.155;95%CI: 2.234-7.730;P < 0.001) asindependent predictors of mortality after transplantation. The pre-operative dialysisperiod was not statistically significant.CONCLUSIONThese findings suggest that early graft dysfunction, rather than dialysis duration, may serve as a critical risk factorfor poor transplant outcomes.展开更多
BACKGROUND In a previous paper,we reported a high prevalence of donor-specific antibody(DSA)in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.AIM...BACKGROUND In a previous paper,we reported a high prevalence of donor-specific antibody(DSA)in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.AIM To clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients.METHODS We performed a retrospective analysis of 123 pediatric liver transplantation(LT)recipients who participated in yearly follow-ups including Luminex testing for DSA at our center.The cohort was split into two groups according to the DSA status(DSA-positive n=54,DSA-negative n=69).Groups were compared with regard to liver function,biopsy findings,graft survival,need for re-LT and immunosuppressive medication.RESULTS DSA-positive pediatric patients showed a higher prevalence of chronic rejection(P=0.01),fibrosis(P<0.001)and re-transplantation(P=0.018)than DSA-negative patients.Class II DSAs particularly influenced graft survival.Alleles DQ2,DQ7,DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis.Mean fluorescence intensity levels and DSA number did not impact graft survival.Previous episodes of chronic rejection might lead to DSA development.CONCLUSION DSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT.Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibodymediated rejection improved early identification of patients at risk of graft loss.展开更多
Hepatic ischemia-reperfusion injury is an important mechanism of liver failure that occurs in many clinical conditions,including massive hemorrhage,major hepatectomy and liver transplantation,and leads to poor outcome...Hepatic ischemia-reperfusion injury is an important mechanism of liver failure that occurs in many clinical conditions,including massive hemorrhage,major hepatectomy and liver transplantation,and leads to poor outcomes.The underlying cellular and molecular reactions are extremely complex and not completely understood.Anaerobic metabolism,ATP depletion,intracellular acidosis,calcium overload,mitochondrial dysfunction,oxidative stress,activation of Kupffer cells and neutrophils,platelet aggregation,nitric oxide production,activation of the complement system and overexpression of cytokines and chemokines constitute the main pathophysiological actions and pathways for possible therapeutic strategies.Prostaglandins(PGs)are a group of biologically active lipid compounds called eicosanoids with many physiological activities.Prostacyclin(PGI_(2))is a member of the PGs family with an unstable chemical structure and a very short half-life.PGI_(2)has potent vasodilating activity,inhibits platelet activation and exerts anti-inflammatory effects.PGI_(2)has been evaluated in chronic liver disease as a mediator of hepatic stellate cell function,an antiproliferative and antifibrotic agent and a regulator of the hepatic microcirculation.In recent decades,the cytoprotective effects of PGI_(2)analogs on hepatic ischemiareperfusion injury have been experimentally and clinically studied.Moreover,the administration of synthetic PGI_(2)analogs to patients who underwent liver transplantation produced very encouraging results.The downregulation of PGE_(2) production,reduction of neutrophil aggregation in liver lobules,regulation of local microcirculatory homeostasis,improvement in mitochondrial function,alleviation of hepatic oxidative stress,suppression of the c-Jun N-terminal kinase and p38 cascades and downregulation of tumor necrosis factor-alpha and interleukin-1βproduction constitute some of the underlying physiological mechanisms of the beneficial effects of PGI_(2)on hepatic ischemia-reperfusion injury.Thus,PGI_(2)analogs appear to hold great promise for the management of hepatic ischemia-reperfusion injury,but further research is needed.展开更多
BACKGROUND Portal vein arterialization(PVA)has been used in liver transplantation(LT)to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for co...BACKGROUND Portal vein arterialization(PVA)has been used in liver transplantation(LT)to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis(PVT).The effect of PVA on portal perfusion and primary graft dysfunction(PGD)has not been assessed.All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed.To account for the time-sensitive effects of graft perfusion,patients were classified into two groups:prereperfusion(pre-PVA),if the arterioportal anastomosis was performed before graft revascularization,and postreperfusion(post-PVA),if PVA was performed afterward.The pre-PVA rationale contemplated poor portal hemodynamics,severe vascular steal,or PVT.Post-PVA was considered if graft hypoperfusion became evident.Conservative interventions were attempted before PVA.展开更多
The use of extracorporeal membrane oxygenation(ECMO)in the field of lung transplantation has rapidly expanded over the past 30 years.It has become an important tool in an increasing number of specialized centers as a ...The use of extracorporeal membrane oxygenation(ECMO)in the field of lung transplantation has rapidly expanded over the past 30 years.It has become an important tool in an increasing number of specialized centers as a bridge to transplantation and in the intra-operative and/or post-operative setting.ECMO is an extremely versatile tool in the field of lung transplantation as it can be used and adapted in different configurations with several potential cannulation sites according to the specific need of the recipient.For example,patients who need to be bridged to lung transplantation often have hypercapnic respiratory failure that may preferably benefit from veno-venous(VV)ECMO or peripheral veno-arterial(VA)ECMO in the case of hemodynamic instability.Moreover,in an intraoperative setting,VV ECMO can be maintained or switched to a VA ECMO.The routine use of intra-operative ECMO and its eventual prolongation in the postoperative period has been widely investigated in recent years by several important lung transplantation centers in order to assess the graft function and its potential protective role on primary graft dysfunction and on ischemia-reperfusion injury.This review will assess the current evidence on the role of ECMO in the different phases of lung transplantation,while analyzing different studies on pre,intra-and post-operative utilization of this extracorporeal support.展开更多
Lung transplantation(LT)is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease.Furthermore,as a therapeutic option for high-risk candidates,single LT(SLT)can be feasible ...Lung transplantation(LT)is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease.Furthermore,as a therapeutic option for high-risk candidates,single LT(SLT)can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single(double)LT(SSLTx).Still,the long-term overall survival is,in general,better for SSLTx.Despite the great success over the years,the early post-SLT period remains a perilous time for these patients.Patients who undergo SLT are predisposed to evolving early or late postoperative complications.This review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction,native lung complications,anastomosis complications,infections,cardiovascular,gastrointestinal,renal,and metabolite complications,and their association with morbidity and mortality in these patients.Furthermore,we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.展开更多
Lung ischemia-reperfusion injury(IRI)stands as the primary culprit behind primary graft dysfunction(PGD)after lung transplantation,yet viable therapeutic options are lacking.In the present study,we used a murine hilar...Lung ischemia-reperfusion injury(IRI)stands as the primary culprit behind primary graft dysfunction(PGD)after lung transplantation,yet viable therapeutic options are lacking.In the present study,we used a murine hilar clamp(1 h)and reperfusion(3 h)model to study IRI.The left lung tissues were harvested for metabolomics,transcriptomics,and single-cell RNA sequencing.Metabolomics of plasma from human lung transplantation recipients was also performed.Lung histology,pulmonary function,pulmonary edema,and survival analysis were measured in mice.Integrative analysis of metabolomics and transcriptomics revealed a marked up-regulation of arachidonate 12-lipoxygenase(ALOX12)and its metabolite 12-hydroxyeicosatetraenoic acid(12-HETE),which played a pivotal role in promoting ferroptosis and neutrophil extracellular trap(NET)formation during lung IRI.Additionally,single-cell RNA sequencing revealed that ferroptosis predominantly occurred in pulmonary endothelial cells.Importantly,Alox12-knockout(KO)mice exhibited a notable decrease in ferroptosis,NET formation,and tissue injury.To investigate the interplay between endothelial ferroptosis and NET formation,a hypoxia/reoxygenation(HR)cell model using 2 human endothelial cell lines was established.By incubating conditioned medium from HR cell model with neutrophils,we found that the liberation of high mobility group box1(HMGB1)from endothelial cells undergoing ferroptosis facilitated the formation of NETs by activating the TLR4/MYD88 pathway.Last,the administration of ML355,a targeted inhibitor of Alox12,mitigated lung IRI in both murine hilar clamp/reperfusion and rat left lung transplant models.Collectively,our study indicates ALOX12 as a promising therapeutic strategy for lung IRI.展开更多
文摘BACKGROUND: Primary graft dysfunction (PGD) causes complications in liver transplantation, which result in poor prognosis. Recipients who develop PGD usually experience a longer intensive care unit and hospital stay and have higher mortality and graft loss rates compared with those without graft dysfunction. However, because of the lack of universally accepted definition, early diagnosis of graft dysfunction is difficult. Additionally, numerous factors affect the allograft function after transplantation, making the prediction of PGD more difficult. The present review was to analyze the literature available on PGD and to propose a definition.DATA SOURCE: A search of PubMed (up to the end of 2012) for English-language articles relevant to PGD was performed to clarify the characteristics, risk factors, and possible treatments or interventions for PGD.RESULTS: There is no pathological diagnostic standard; many documented definitions of PGD are different. Many factors such as donor status, procurement and transplant process and recipient illness may affect the function of graft, and ischemia reperfusion injury is considered the direct cause. Potentia managements which are helpful to improve graft function were investigated. Some of them are promising.CONCLUSIONS: Our analyses suggested that the definition of PGD should include one or more of the following variables: (1)bilirubin ≥10 mg/dL on postoperative day 7; (2) internationa normalized ratio ≥1.6 on postoperative day 7; and (3) alanine aminotransferase or aspartate aminotransferase 】2000 IU/L within 7 postoperative days. Reducing risk factors may decrease the incidence of PGD. A majority of the recipients could recover from PGD; however, when the graft progresses intoprimary non-function, the patients need to be treated with retransplantation.
基金Supported by National Basic Research Program (973) of China, No. 2007CB513005, No. 2009CB522401 and No. 2009CB522406
文摘AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The whole experiment was divided into three groups: (1) Normal group (n = 12): normal BN rats without any drug or operation; (2) SGT group (syngeneic transplant of BN-BN, n = 12): both donors and recipients were BN rats; and (3) AGT group (allogeneic transplant of LEW-BN, n = 12): Donors were Lewis and recipients were BN rats. In the AGT group, all recipients were subcutaneously injected by Cyclosporin A after LT. Survival time was observed for 1 year. All the dying rats were sampled, biliary tract tissues were performed bacterial culture and liver tissues for histological study. Twenty-one d after LT, 8 rats were selected randomly in each group for sampling. Blood samples from caudal veins were collected for measurements of plasma endotoxin, cytokines and metabonomic analysis, and faeces were analyzed for intestinal microflora. RESULTS: During the surgery of LT, no complications of blood vessels or bile duct happened, and all rats in each group were still alive in the next 2 wk. The long term observation revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft diseases, 5 rats in which died of chronic bile duct hyperplasia. Compared to the SGT and normal groups, survival ratio of rats significantly decreased in the AGT group (aP < 0.01, bP < 0.001, respectively). Moreover, liver necrosis, liver infection, and severe chronic bile duct hyperplasia were observed in the AGT group by H and E stain. On 21 d after LT, compared with the normal group (25.38 ± 7.09 ng/L) and SGT group (33.12 ± 10.26 ng/L), plasma endotoxin in the AGT group was remarkably increased (142.86 ± 30.85 ng/L) (both P < 0.01). Plasma tumor necrosis factor-α and interleukin-6 were also significantly elevated in the AGT group (593.6 ± 171.67 pg/mL, 323.8 ± 68.30 pg/mL) vs the normal (225.5 ± 72.07 pg/mL, 114.6 ± 36.67 pg/mL) and SGT groups (321.3 ± 88.47 pg/mL, 205.2 ± 53.06 pg/mL) (P < 0.01). Furthermore, Bacterial cultures of bile duct tissues revealed that the rats close to death from the SGT and AGT groups were strongly positive, while those from the normal group were negative. The analysis of intestinal microflora was performed. Compared to the normal group (7.98 ± 0.92, 8.90 ± 1.44) and SGT group (8.51 ± 0.46, 9.43 ± 0.69), the numbers of Enterococcus and Enterobacteria in the AGT group (8.76 ± 1.93, 10.18 ± 1.64) were significantly increased (both aP < 0.01, bP < 0.05, respectively). Meanwhile, compared to the normal group (9.62 ± 1.60, 9.93 ± 1.10) and SGT group (8.95 ± 0.04, 9.02 ± 1.14), the numbers of Bifidobacterium and Lactobacillus in the AGT group (7.83 ± 0.72, 8.87± 0.13) were remarkably reduced (both aP < 0.01, bP < 0.05, respectively). In addition, metabonomics analysis showed that metabolic profiles of plasma in rats in the AGT group were severe deviated from the normal and SGT groups. CONCLUSION: Chronic bile duct hyperplasia is a pathological type of CGD following LT in rats. The mechanism of this kind of CGD is associated with the alterations of inflammation, intestinal barrier function and microflora as well as plasma metabolic profiles.
文摘AIM:To describe a condition that we define as early graft dysfunction(EGD)which can be identified preoperatively. METHODS:Small-for-size graft dysfunction following living-related liver transplantation(LRLT)is characterized by EGD when the graft-to-recipient body weight ratio(GRBWR)is below 0.8%.However, patients transplanted with GRBWR above 0.8%can develop dysfunction of the graft.In 73 recipients of LRLT(GRBWR>0.8%),we identified 10 patients who developed EGD.The main measures of outcomes analyzed were overall mortality,number of re-transplants and length of stay in days(LOS).Furthermore we analyzed other clinical pre-transplant variables,intraoperative parameters and post transplant data.RESULTS:A trend in favor of the non-EGD group(3-mo actuarial survival 98%vs 88%,P=0.09;3-mo graft mortality 4.7%vs 20%,P=0.07)was observed as well as shorter LOS(13 d vs 41.5 d;P=0.001)and smaller requirement of peri-operative Units of Plasma (4 vs 14;P=0.036).Univariate analysis of pre- transplant variables identified platelet count,serum bilirubin,INR and Meld-Na score as predictors of EGD. In the multivariate analysis transplant Meld-Na score (P=0.025,OR:1.175)and pretransplant platelet count(P=0.043,OR:0.956)were independently associated with EGD. CONCLUSION:EGD can be identified preoperatively and is associated with increased morbidity after LRLT. A prompt recognition of EGD can trigger a timely treatment.
文摘Lung transplantation is the treatment of choice for patients with end-stage lung disease.Currently,just under 5000 lung transplants are performed worldwide annually.However,a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction.It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant.This review aims to provide an in-depth analysis of the epidemiology,pathophysiology,risk factors,outcomes,and future frontiers involved in mitigating primary graft dysfunction.The current diagnostic criteria are examined alongside changes from the previous definition.We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion.Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality,ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.
文摘BACKGROUNDThe impact of long-term dialysis (LTD) therapy on the survival benefit of kidneytransplantation compared to short-term dialysis (STD) remains unclear. Additionally,donor organ quality has been identified as a significant predictor ofpatient survival in deceased donor kidney transplantation.AIMTo investigate the effects of the best graft function within three months posttransplant,as well as dialysis duration, on transplant outcomes.METHODSA total of 255 patients were included in this retrospective cohort study. Patientswere divided into two groups: Those with LTD (≥ 15 years;Group LTD) and thosewith STD (< 15 years;Group STD). Clinical backgrounds and outcomes werecompared between the groups.RESULTSGroup LTD comprised 28 patients, while Group STD included 227 patients. Therewere no significant differences between the two groups in terms of age at transplant,donor age, lowest serum creatinine (best S-Cr) within three months posttransplant,or the frequency of cardiovascular events after transplantation. Multivariateanalysis identified age [hazard ratio (HR): 1.058;95%CI: 1.002-1.116;P =0.040], post-transplant incidence of cardiovascular disease (HR: 20.264;95%CI:6.052-67.850;P < 0.001), and best S-Cr (HR: 4.155;95%CI: 2.234-7.730;P < 0.001) asindependent predictors of mortality after transplantation. The pre-operative dialysisperiod was not statistically significant.CONCLUSIONThese findings suggest that early graft dysfunction, rather than dialysis duration, may serve as a critical risk factorfor poor transplant outcomes.
文摘BACKGROUND In a previous paper,we reported a high prevalence of donor-specific antibody(DSA)in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.AIM To clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients.METHODS We performed a retrospective analysis of 123 pediatric liver transplantation(LT)recipients who participated in yearly follow-ups including Luminex testing for DSA at our center.The cohort was split into two groups according to the DSA status(DSA-positive n=54,DSA-negative n=69).Groups were compared with regard to liver function,biopsy findings,graft survival,need for re-LT and immunosuppressive medication.RESULTS DSA-positive pediatric patients showed a higher prevalence of chronic rejection(P=0.01),fibrosis(P<0.001)and re-transplantation(P=0.018)than DSA-negative patients.Class II DSAs particularly influenced graft survival.Alleles DQ2,DQ7,DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis.Mean fluorescence intensity levels and DSA number did not impact graft survival.Previous episodes of chronic rejection might lead to DSA development.CONCLUSION DSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT.Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibodymediated rejection improved early identification of patients at risk of graft loss.
文摘Hepatic ischemia-reperfusion injury is an important mechanism of liver failure that occurs in many clinical conditions,including massive hemorrhage,major hepatectomy and liver transplantation,and leads to poor outcomes.The underlying cellular and molecular reactions are extremely complex and not completely understood.Anaerobic metabolism,ATP depletion,intracellular acidosis,calcium overload,mitochondrial dysfunction,oxidative stress,activation of Kupffer cells and neutrophils,platelet aggregation,nitric oxide production,activation of the complement system and overexpression of cytokines and chemokines constitute the main pathophysiological actions and pathways for possible therapeutic strategies.Prostaglandins(PGs)are a group of biologically active lipid compounds called eicosanoids with many physiological activities.Prostacyclin(PGI_(2))is a member of the PGs family with an unstable chemical structure and a very short half-life.PGI_(2)has potent vasodilating activity,inhibits platelet activation and exerts anti-inflammatory effects.PGI_(2)has been evaluated in chronic liver disease as a mediator of hepatic stellate cell function,an antiproliferative and antifibrotic agent and a regulator of the hepatic microcirculation.In recent decades,the cytoprotective effects of PGI_(2)analogs on hepatic ischemiareperfusion injury have been experimentally and clinically studied.Moreover,the administration of synthetic PGI_(2)analogs to patients who underwent liver transplantation produced very encouraging results.The downregulation of PGE_(2) production,reduction of neutrophil aggregation in liver lobules,regulation of local microcirculatory homeostasis,improvement in mitochondrial function,alleviation of hepatic oxidative stress,suppression of the c-Jun N-terminal kinase and p38 cascades and downregulation of tumor necrosis factor-alpha and interleukin-1βproduction constitute some of the underlying physiological mechanisms of the beneficial effects of PGI_(2)on hepatic ischemia-reperfusion injury.Thus,PGI_(2)analogs appear to hold great promise for the management of hepatic ischemia-reperfusion injury,but further research is needed.
文摘BACKGROUND Portal vein arterialization(PVA)has been used in liver transplantation(LT)to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis(PVT).The effect of PVA on portal perfusion and primary graft dysfunction(PGD)has not been assessed.All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed.To account for the time-sensitive effects of graft perfusion,patients were classified into two groups:prereperfusion(pre-PVA),if the arterioportal anastomosis was performed before graft revascularization,and postreperfusion(post-PVA),if PVA was performed afterward.The pre-PVA rationale contemplated poor portal hemodynamics,severe vascular steal,or PVT.Post-PVA was considered if graft hypoperfusion became evident.Conservative interventions were attempted before PVA.
文摘The use of extracorporeal membrane oxygenation(ECMO)in the field of lung transplantation has rapidly expanded over the past 30 years.It has become an important tool in an increasing number of specialized centers as a bridge to transplantation and in the intra-operative and/or post-operative setting.ECMO is an extremely versatile tool in the field of lung transplantation as it can be used and adapted in different configurations with several potential cannulation sites according to the specific need of the recipient.For example,patients who need to be bridged to lung transplantation often have hypercapnic respiratory failure that may preferably benefit from veno-venous(VV)ECMO or peripheral veno-arterial(VA)ECMO in the case of hemodynamic instability.Moreover,in an intraoperative setting,VV ECMO can be maintained or switched to a VA ECMO.The routine use of intra-operative ECMO and its eventual prolongation in the postoperative period has been widely investigated in recent years by several important lung transplantation centers in order to assess the graft function and its potential protective role on primary graft dysfunction and on ischemia-reperfusion injury.This review will assess the current evidence on the role of ECMO in the different phases of lung transplantation,while analyzing different studies on pre,intra-and post-operative utilization of this extracorporeal support.
文摘Lung transplantation(LT)is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease.Furthermore,as a therapeutic option for high-risk candidates,single LT(SLT)can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single(double)LT(SSLTx).Still,the long-term overall survival is,in general,better for SSLTx.Despite the great success over the years,the early post-SLT period remains a perilous time for these patients.Patients who undergo SLT are predisposed to evolving early or late postoperative complications.This review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction,native lung complications,anastomosis complications,infections,cardiovascular,gastrointestinal,renal,and metabolite complications,and their association with morbidity and mortality in these patients.Furthermore,we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.
基金supported by the National Key Research and Development Program of China(grant no.2024YFC3044600)Scientific and Technological Innovation Action Plans of Science and Technology Commission of Shanghai Municipality(nos.20DZ2253700,22Y2190050,and SHDC22021310-A)+1 种基金Ningbo Top Medical and Health Research Program(no.2022030208)The Young Talent Program of Shanghai Pulmonary Hospital(no.FKCY2302).
文摘Lung ischemia-reperfusion injury(IRI)stands as the primary culprit behind primary graft dysfunction(PGD)after lung transplantation,yet viable therapeutic options are lacking.In the present study,we used a murine hilar clamp(1 h)and reperfusion(3 h)model to study IRI.The left lung tissues were harvested for metabolomics,transcriptomics,and single-cell RNA sequencing.Metabolomics of plasma from human lung transplantation recipients was also performed.Lung histology,pulmonary function,pulmonary edema,and survival analysis were measured in mice.Integrative analysis of metabolomics and transcriptomics revealed a marked up-regulation of arachidonate 12-lipoxygenase(ALOX12)and its metabolite 12-hydroxyeicosatetraenoic acid(12-HETE),which played a pivotal role in promoting ferroptosis and neutrophil extracellular trap(NET)formation during lung IRI.Additionally,single-cell RNA sequencing revealed that ferroptosis predominantly occurred in pulmonary endothelial cells.Importantly,Alox12-knockout(KO)mice exhibited a notable decrease in ferroptosis,NET formation,and tissue injury.To investigate the interplay between endothelial ferroptosis and NET formation,a hypoxia/reoxygenation(HR)cell model using 2 human endothelial cell lines was established.By incubating conditioned medium from HR cell model with neutrophils,we found that the liberation of high mobility group box1(HMGB1)from endothelial cells undergoing ferroptosis facilitated the formation of NETs by activating the TLR4/MYD88 pathway.Last,the administration of ML355,a targeted inhibitor of Alox12,mitigated lung IRI in both murine hilar clamp/reperfusion and rat left lung transplant models.Collectively,our study indicates ALOX12 as a promising therapeutic strategy for lung IRI.
