BACKGROUND： In patients with end-stage fiver disease, fiver transplantation is the only available curative treatment. Al- though the outcome and quality of life in the patients have improved over the past decades, pr...BACKGROUND： In patients with end-stage fiver disease, fiver transplantation is the only available curative treatment. Al- though the outcome and quality of life in the patients have improved over the past decades, primary dys- or nonfimction （PDF/PNF） can occur. Early detection of PDF and PNF is crucial and could lead to individual therapies. This study was designed to identify early markers of reperfusion injury and PDF in liver biopsies taken during the first hour after reperfusion.展开更多
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
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
BACKGROUND Primary ciliary dyskinesia(PCD)is a rare genetic disorder caused by motile cilia dysfunction.Identifying pathogenic variants is essential for diagnosis and personalized care,especially in consanguineous pop...BACKGROUND Primary ciliary dyskinesia(PCD)is a rare genetic disorder caused by motile cilia dysfunction.Identifying pathogenic variants is essential for diagnosis and personalized care,especially in consanguineous populations like Saudi Arabia.CASE SUMMARY This report presents a Saudi pediatric patient diagnosed with PCD who exhibited persistent neonatal tachypnea,chronic productive cough,and recurrent otitis media.Whole-exome sequencing revealed a novel homozygous nonsense variant in the C3orf67 gene(NM_198463.2:c.508C>T),resulting in a truncated,nonfunctional protein.This mutation likely impairs ciliary motility due to the production of a truncated,non-functional protein.The clinical findings were supported by multiple positive sputum cultures and a significant family history of similar symptoms,suggesting a genetic etiology consistent with autosomal recessive inheritance.CONCLUSION This case highlights the importance of genetic studies in diagnosing PCD,particularly in communities with a high rate of consanguinity.The identification of a novel homozygous variant in the C3orf67 gene expands the known genetic landscape of the disease.Further research is essential to clarify the functional role of C3orf67 in ciliary biology and its contribution to PCD pathogenesis.展开更多
The probability of developing primary dysfunction(PD)is a function of the probability of ischemia/reperfusion(I/R)injury.The probability of I/R injury in turn,is a function of several donor and transplantation process...The probability of developing primary dysfunction(PD)is a function of the probability of ischemia/reperfusion(I/R)injury.The probability of I/R injury in turn,is a function of several donor and transplantation process variables,among which is ischemia time.Custodio et al studied the duration of a special type of warm ischemia and showed,contrary to what is known,that a longer duration is not statistically different from a shorter one in PD development.This finding opens the door to the unforeseen opportunity of training fellows in performing hepatectomies,since the duration will not jeopardize liver transplant outcomes,albeit with some precautions.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
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
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
基金supported by an unrestricted grant from Novartis Pharma Gmb H,Nürnberg,Germany
文摘BACKGROUND： In patients with end-stage fiver disease, fiver transplantation is the only available curative treatment. Al- though the outcome and quality of life in the patients have improved over the past decades, primary dys- or nonfimction （PDF/PNF） can occur. Early detection of PDF and PNF is crucial and could lead to individual therapies. This study was designed to identify early markers of reperfusion injury and PDF in liver biopsies taken during the first hour after reperfusion.
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.
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BACKGROUND Primary ciliary dyskinesia(PCD)is a rare genetic disorder caused by motile cilia dysfunction.Identifying pathogenic variants is essential for diagnosis and personalized care,especially in consanguineous populations like Saudi Arabia.CASE SUMMARY This report presents a Saudi pediatric patient diagnosed with PCD who exhibited persistent neonatal tachypnea,chronic productive cough,and recurrent otitis media.Whole-exome sequencing revealed a novel homozygous nonsense variant in the C3orf67 gene(NM_198463.2:c.508C>T),resulting in a truncated,nonfunctional protein.This mutation likely impairs ciliary motility due to the production of a truncated,non-functional protein.The clinical findings were supported by multiple positive sputum cultures and a significant family history of similar symptoms,suggesting a genetic etiology consistent with autosomal recessive inheritance.CONCLUSION This case highlights the importance of genetic studies in diagnosing PCD,particularly in communities with a high rate of consanguinity.The identification of a novel homozygous variant in the C3orf67 gene expands the known genetic landscape of the disease.Further research is essential to clarify the functional role of C3orf67 in ciliary biology and its contribution to PCD pathogenesis.
文摘The probability of developing primary dysfunction(PD)is a function of the probability of ischemia/reperfusion(I/R)injury.The probability of I/R injury in turn,is a function of several donor and transplantation process variables,among which is ischemia time.Custodio et al studied the duration of a special type of warm ischemia and showed,contrary to what is known,that a longer duration is not statistically different from a shorter one in PD development.This finding opens the door to the unforeseen opportunity of training fellows in performing hepatectomies,since the duration will not jeopardize liver transplant outcomes,albeit with some precautions.
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.
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.
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.
