RESUMO
Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.
RESUMO
BACKGROUND AND AIM: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. MATERIALS AND METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.
RESUMO
BACKGROUND: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers. METHODS: Six diseased livers recovered from LT recipients with different diagnoses were collected. The diseased livers were connected to the machine perfusion system that circulated tailored perfusate, providing oxygen and nutrients. The pressure and flow of the system were recorded, and blood gas analysis and laboratory tests of perfusate and bile were examined to analyze the function of the diseased livers. Liver tissues before and after NMP were collected for histological analysis. RESULTS: Experiments showed that the system maintained the diseased livers in a physiological state, ensuring stable hemodynamics and a suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory tests demonstrated a restoration and sustenance of metabolism with minimal damage. Notably, a majority of the diseased livers exhibited bile production continuously, signifying their vivid functional integrity. The pathological characteristics remained stable before and after NMP. CONCLUSION: We successfully established the machine perfusion system tailored specifically for diseased human whole livers. Through the application of this system, we have developed a novel in vitro model that faithfully recapitulates the main features of human liver disease. This model holds immense promise as an advanced disease modeling platform, offering profound insights into liver diseases and potential implications for research and therapeutic development.
Assuntos
Transplante de Fígado , Fígado , Preservação de Órgãos , Perfusão , Humanos , Perfusão/métodos , Perfusão/instrumentação , Transplante de Fígado/métodos , Fígado/cirurgia , Fígado/patologia , Preservação de Órgãos/métodos , Preservação de Órgãos/instrumentação , Masculino , Pessoa de Meia-Idade , Feminino , Hepatopatias/patologiaRESUMO
BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.
Assuntos
Doença Hepática Terminal , Transplante de Fígado , Traumatismo por Reperfusão , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Doença Hepática Terminal/complicações , Isquemia/patologia , Fígado/patologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/patologia , Perfusão/métodos , Preservação de Órgãos/métodosRESUMO
Immune checkpoint inhibitors (ICIs) may lead to rejection and even graft loss of solid organ transplant recipients, making them not widely used in transplant patients. There is insufficient clinical experience in using ICIs as a bridging or downstaging therapy before transplantation. We performed a retrospective review of patients receiving programmed cell death 1 inhibitor (PD1) before liver transplantation for HCC in our center and analyzed the data of these patients with the purpose of investigating the safety and feasibility of preoperative PD1 inhibitor among liver transplant recipients and exploring the preoperative correlation ICIs and the postoperative risk of rejection and immune-related graft loss. A total of 16 patients enrolled in this study. Acute rejection occurred in 9 patients, with an incidence of 56.3%. The median time of rejection was 7 days after surgery. The median FK506 concentration at the time of rejection was 7.1 µg/L. All rejection reactions were reversed after adjusting the immunosuppression regimen. The interval between the last PD1 inhibitor and transplantation in the rejection group was shorter than that in the nonrejection group, and there was a statistical difference [21.0 (15.5-27.5) days vs. 60.0 (34.0-167.0) days, p =0.01]. In conclusion, PD1 inhibitor is a safe and feasible method for bridging or downstaging treatment before liver transplantation. Although preoperative PD1 inhibitor may increase the incidence of postoperative rejection, it is not associated with increased immune-related graft loss and patient death.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Carcinoma Hepatocelular/cirurgia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Neoplasias Hepáticas/cirurgia , ApoptoseRESUMO
BACKGROUND: Normothermic machine perfusion (NMP) provides a novel platform to preserve isolated organs in an artificial condition. Our study aimed to explore the interaction between the liver and kidney at an ex vivo organ level by adding a liver to the kidney NMP circuit. METHODS: Porcine kidney and liver obtained from abattoir were subjected to 9 h NMP after suffering 30-min warm ischemia time and 90-min cold ischemia time. The liver-kidney NMP group (n = 5) and the single-kidney NMP group (n = 5) were designed. During the NMP, perfusion parameters, blood gas analysis, and tissue samples were compared. RESULTS: The perfusate of both groups remained stable, and continuous urine production was observed during NMP. In the liver-kidney NMP group, the lactate level was low, while blood urea nitrogen increased and glucose levels decreased. After the NMP, the renal tissue in the liver-kidney group exhibited fewer histological changes such as tubular epithelium vacuolization, along with reduced expression of IL-6, IL-8, IL-1ß, NLRP3, and GSDMD. CONCLUSIONS: Our results indicated that the expression of renal pro-inflammatory factors was reduced in the liver-kidney NMP system.
Assuntos
Fígado , Preservação de Órgãos , Suínos , Animais , Preservação de Órgãos/métodos , Perfusão/métodos , Rim/patologia , Isquemia Quente/métodosRESUMO
BACKGROUND: The hepatocellular carcinoma (HCC) belongs to a common malignancy especially in China. Recent data have clarified important roles of long non-coding RNAs (lncRNAs) in HCC. However, the role of a novel intergenic lncRNA termed TGLC15 is still elusive. METHODS: We screened for novel lncRNAs using lncRNA profiling. TGLC15 expression was quantified by qRT-PCR. In vitro experiments such as migration and viability assays were performed. In vivo implantation experiments were conducted to investigate tumorigenic functions of TGLC15. Combined RNA immunoprecipitation (RIP) and mass spectrometry (MS) were utilized to uncover Sox4 as TGLC15 binding protein. RESULTS: TGLC15 is significantly overexpressed in tumor tissues and HCC cell lines. Higher TGLC15 levels correlated with advanced malignant characteristics such as TNM stages, tumor size, and metastasis. TGLC15 advanced HCC migration and viability. The in vivo experiments supported that xenograft tumor growth and proliferation were facilitated by TGLC15 overexpression. Mechanistic studies showed that TGLC15 interacted with Sox4 and interaction between TGLC15 and Sox4 could stabilize Sox4 via reduction in proteasome-mediated degradation. CONCLUSIONS: Collectively, our data have identified a novel lncRNA TGLC15 during HCC development. The TGLC15-Sox4 signaling might be a potential target for pharmaceutical intervention.
Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/metabolismo , Fatores de Transcrição SOXC/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Humanos , Estabilidade Proteica , Proteólise , RNA Longo não Codificante/genéticaRESUMO
In this paper, a glutathione functionalized gold nanocluster (GSH-AuNCs) was prepared. GSH-AuNCs can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide to produce a blue-green ox-TMB. By using its peroxidase activity and the GSH-AuNCs-TMB-H2O2 system, the visualization of Fe3+ and Cu2+ and the high sensitivity detection of Fe3+ and Cu2+ can be realized according to the change of absorbance value and color of the system. The results showed that the sensitivity of the system to detect Fe3+ and Cu2+ in industrial wastewater reached 1.25 × 10-9 M and 1.25 × 10-10M, respectively. At the same time, the chelating agents NH4F and EDTA · 2Na were introduced to realize the selective detection of the two ions under the coexistence of Fe3+ and Cu2+ ions.
Assuntos
Ouro , Nanopartículas Metálicas , Colorimetria , Glutationa , Peróxido de Hidrogênio , Limite de DetecçãoRESUMO
The dynamic and residues of florasulam and flumetsulam in corn field ecosystem were investigated using quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The limits of quantification (LOQs) of the proposed method ranged from 0.005 to 0.01 mg/kg. Mean recoveries and relative standard deviations (RSDs) of the two compounds in all samples at three spiking levels ranged 94-110 % and 2.0-9.2 %, respectively. Florasulam and flumetsulam degradation followed first-order kinetics with half-lives 1.7-2.9 and 3.3-8.7 days in soil and 1.3-1.8 and 0.9-1.7 days in plant, respectively. The residues in all the samples were found to be less than the LOQs at preharvest intervals of 53 and 78 days. The results suggest that the combined use of florasulam and flumetsulam on corn is considered to be safe under the recommended conditions and can be utilized for establishing the maximum residue limit (MRL) of florasulam in corn in China.
Assuntos
Monitoramento Ambiental , Herbicidas/análise , Resíduos de Praguicidas/análise , Pirimidinas/administração & dosagem , Pirimidinas/análise , Sulfonamidas/administração & dosagem , Sulfonamidas/análise , Zea mays , China , Cromatografia Líquida , Ecossistema , Meia-Vida , Cinética , Espectrometria de Massas , Solo/química , Poluentes do Solo/análise , Espectrometria de Massas em TandemRESUMO
An integrated method for the simultaneous determination of insecticide fipronil and its three metabolites, desulfinyl, sulfide, and sulfone, in maize grain, maize stem, and soil was developed. This three-step method uses liquid-solid extraction with ultrasound or mechanical grinding, followed by liquid-liquid partitioning and florisil solid-phase extraction (SPE) for cleanup. The quantification was conducted by gas chromatography-electron capture detection in triplicate for each sample. The method was validated with five replicates at three fortification concentrations, 0.002, 0.01, and 0.1 mg kg(-1), in each matrix and gave mean recoveries from 83 to 106 % with relative standard deviation ≤ 8.9 %. The limits of quantification (LOQ) were 0.002 mg kg(-1) for the compounds in all matrixes. In the field study in Beijing and Shandong 2012, fipronil-coated maize seeds were planted and the proposed method was applied for checking the possible existence of four compounds in maize and soil samples, but none of them contained residues higher than the LOQs in both application rates. Moreover, the dissipation of fipronil in soil fits first-order kinetics with half-lives 9.90 and 10.34 days in Beijing and Shandong, respectively. Combined with an adequate sample treatment, this technique offers good sensitivity and selectivity in the three complex matrixes. The results could provide guidance for the further research on pesticide distribution and safe use of fipronil as seed coat in cereals.
Assuntos
Cromatografia Gasosa/métodos , Inseticidas/análise , Pirazóis/análise , Solo/química , Zea mays/metabolismo , Elétrons , Monitoramento Ambiental , Inseticidas/metabolismo , Pirazóis/metabolismo , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Extração em Fase Sólida/métodos , Zea mays/químicaRESUMO
Background: In organ transplantation, ischemia, and reperfusion injury (IRI) is considered as an inevitable event and the major contributor to graft failure. Ischemia-free liver transplantation (IFLT) is a novel transplant procedure that can prevent IRI and provide better transplant outcomes. However, a large animal model of IFLT has not been reported. Therefore, we develop a new, reproducible, and stable model of IFLT in pigs for investigating mechanisms of IFLT in IRI. Methods: Ten pigs were subjected to IFLT or conventional liver transplantation (CLT). Donor livers in IFLT underwent 6-h continuous normothermic machine perfusion (NMP) throughout graft procurement, preservation, and implantation, whereas livers in CLT were subjected to 6-h cold storage before implantation. The early reperfusion injury was compared between the 2 groups. Results: Continuous bile production, low lactate, and liver enzyme levels were observed during NMP in IFLT. All animals survived after liver transplantation. The posttransplant graft function was improved with IFLT when compared with CLT. Minimal histologic changes, fewer apoptotic hepatocytes, less sinusoidal endothelial cell injury, and proinflammatory cytokine (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-α) release after graft revascularization were documented in the IFLT group versus the CLT group. Conclusions: We report that the concept of IFLT is achievable in pigs. This innovation provides a potential strategy to investigate the mechanisms of IRI and provide better transplant outcomes for clinical practice.
RESUMO
Background and Aims: Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation. However, consensus of definition of early allograft failure is lacking. Methods: A retrospective, multicenter study was performed to validate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers. L-GrAFT (L-GrAFT7 and L-GrAFT10) was compared with existing models: the Early Allograft Failure Simplified Estimation (EASE) score, the model of early allograft function (MEAF), and the Early Allograft Dysfunction (EAD) model. Univariate and multivariate logistic regression were used to find risk factors of L-GrAFT high-risk group. Results: L-GrAFT7 had an area under the curve of 0.85 in predicting 90-day graft survival, significantly superior to MEAF [area under the curve (AUC=0.78, p=0.044)] and EAD (AUC=0.78, p=0.006), while there was no statistical significance between the predicting abilities of L-GrAFT7 and EASE (AUC=0.84, p>0.05). Furthermore, L-GrAFT7 maintains good predicting ability in the subgroup of high-donor risk index (DRI) cases (AUC=0.83 vs. MEAF, p=0.007 vs. EAD, p=0.014) and recipients of donors after cardiac death (AUC=0.92 vs. EAD, p<0.001). Through multivariate analysis, pretransplant bilirubin level, units of packed red blood cells, and the DRI score were selected as independent risk factors of a L-GrAFT7 high-risk group. Conclusions: The accuracy of L-GrAFT7 in predicting early allograft failure was validated in a Chinese multicenter cohort, indicating that it has the potential to become an accurate endpoint of clinical practice and transitional study of machine perfusion.
RESUMO
INTRODUCTION: Preservation fluid (PF) contaminations are common in conventional liver transplantation (CLT) and presumably originate from organ or PF exposures to the external environment in a non-strict sterile manner. Such exposures and PF contamination may be avoided in ischaemia-free liver transplantation (IFLT) because of the strict sterile surgical procedures. In this study, the authors evaluated the impact of IFLT on organ PF contamination. METHODS: A post-hoc analysis using data from the first randomized controlled trial of IFLT was performed to compare the incidence, pathogenic spectrum of PF contamination, and incidence of early recipient infection between IFLT and CLT. Multivariable logistic regression was used to explore risk factors for PF contamination. RESULTS: Of the 68 cases recruited in the trial, 64 were included in this post-hoc analysis. The incidence of culture-positive PF was 9.4% (3/32) in the IFLT group versus 78.1% (25/32) in the CLT group ( P <0.001). Three microorganisms were isolated from PF in the IFLT group, while 43 were isolated in the CLT group. The recipient infection rate within postoperative day 14 was 3.1% (1/32) in the IFLT group vs 15.6% (5/32) in the CLT group, although this difference did not reach statistical significance ( P =0.196). Multivariate analysis revealed that adopting IFLT is an independent protective factor for culture-positive PF. CONCLUSION: PF contamination is substantially decreased in IFLT, and IFLT application is an independent protective factor for PF contamination. Using rigorous sterile measures and effective antibiotic therapy during IFLT may decrease PF contamination.
Assuntos
Transplante de Fígado , Soluções para Preservação de Órgãos , Preservação de Órgãos , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Adulto , IdosoRESUMO
Ningnanmycin is a novel biochemical pesticide which was now used extensively in China. A fast and simple method using high-performance liquid chromatography with ultraviolet detection coupled with solid phase extraction was developed and validated for determination of ningnanmycin in cucumber and soil. The recoveries of ningnanmycin from the fortified cucumber and soil samples ranged from 80.7 % to 107.7 % with relative standard deviations less than 6.6 %. Limits of quantification of the method for both cucumber and soil were 0.02 mg kg(-1). The proposed method was successfully applied to determine the dissipation and residues of ningnanmycin in cucumber and soil under field conditions. Direct confirmation of the analytes in samples was realized by liquid chromatography-mass spectrometry.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cucumis sativus/metabolismo , Fungicidas Industriais/farmacocinética , Resíduos de Praguicidas/farmacocinética , Poluentes do Solo/farmacocinética , Espectrofotometria Ultravioleta/métodos , Calibragem , Limite de Detecção , Espectrometria de MassasRESUMO
In today's booming society and in the age of science and technology, the diversification of food processing methods, the continuous extension of the food trade chain, and the potential hazard factors in the food production process all make people pay more and more attention to the establishment, development, and improvement of the hazard analysis and critical control points (HACCP) system. Only terminal control and post-processing supervision of food can guarantee the absolute safety of food. In the process of processing, it is particularly important to strictly identify and evaluate the food safety hazards. To better assist food production enterprises in establishing and implementing HACCP systems, to implement the primary responsibility of food safety, and to improve the theoretical level and practical application of HACCP system in China, an investigation of the current situation and development frontier of HACCP system in China was conducted. Based on the core journal database of China Knowledge Network, the Chinese Social Science Citation Index database, and the Chinese Science Citation Database as the literature search database platform, the study used the CiteSpace visual metrics software system to analyze 1,084 pieces of literature in the field of HACCP research, in order to track the dynamics and impact of research in this field by Chinese research institutions and major authors, and analyze the research hotspots in the field. It is important for further research on HACCP. The results of the study showed that (1) the number of publications in the field of HACCP in China increased steadily from 1992 to 2004 and then began to decrease; (2) the indexes of journals with more publications were more concentrated, and the journal Food Science published the most; (3) the indexes of major research institutions showed that the cultivation bases of the State Key Laboratory of Chinese Medicinal Materials in the Center of Chinese Medicine Resources of the Chinese Academy of Traditional Medicine, the Guangdong Institute of Occupational Diseases, the Nanchang University of Life Sciences, and the Guangdong Institute of Occupational Diseases were more concentrated. Prevention and Treatment Institute, School of Life Sciences of Nanchang University, China Aquatic Products Quality Certification Center, School of Food Science and Nutrition Engineering of China Agricultural University, and other research structures have the most publications and strong scientific research strength; (4) from the main author indicators, the research in the field of HACCP has formed a total of four more active research teams, involving Chinese herbal medicine, ecological planting, ecological agriculture, occupational disease prevention and treatment, light industry handicrafts, computer software and computer application, agricultural economy, and other research directions. The cooperation between the authors of each team is closer. It is suggested that in terms of food safety requirements, China should not only integrate the traditional supervision measures for food terminals and after the event but also reflect the role of food hazard analysis and assessment in the production process and comprehensively integrate the pre-production, production, and post-production management of food so that food can really be safe.
RESUMO
BACKGROUND: There is no consensus on the usage of extended criteria donor (ECD) grafts in liver transplantation (LT) for acute-on-chronic liver failure (ACLF) patients. AIM: To summarize the experience of using ECD livers in ACLF-LT. METHODS: A retrospective cohort study was conducted, enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021. The patients were divided into ECD and non-ECD groups for analysis. RESULTS: A total of 145 recipients were enrolled in this study, of which ECD and non-ECD recipients accounted for 53.8% and 46.2%, respectively. Donation after cardiac death (DCD) recipients accounted for the minority compared with donation after brain death (DBD) recipients (16.6% vs 83.4%). Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients. ECD grafts were associated with a significantly higher incidence of early allograft dysfunction (EAD) than non-ECD grafts (67.9% vs 41.8%, P = 0.002). Postoperative outcomes between DCD and DBD recipients were comparable (P > 0.05). ECD graft (P = 0.009), anhepatic phase (P = 0.034) and recipient gamma glutamyltransferase (P = 0.016) were independent risk factors for EAD. Recipient preoperative number of extrahepatic organ failures > 2 (P = 0.015) and intraoperative blood loss (P = 0.000) were independent predictors of poor post-LT survival. CONCLUSION: Although related to a higher risk of EAD, ECD grafts can be safely used in ACLF-LT. The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.
Assuntos
Insuficiência Hepática Crônica Agudizada , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Transplante de Fígado/efeitos adversos , Insuficiência Hepática Crônica Agudizada/cirurgia , Insuficiência Hepática Crônica Agudizada/etiologia , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Seleção do Doador , Doadores de Tecidos , Morte Encefálica , Sobrevivência de Enxerto , MorteRESUMO
Introduction: The use of extended criteria donor (ECD) grafts such as donor with infection of hepatitis B virus (HBV) is a potential solution for organ shortage. In this study, we aimed to evaluate the safety and long-term survival of utilization of hepatitis B surface antigen-positive (HBsAg+) donor livers in HCC patients using propensity score matching (PSM) analysis. Methods: Forty-eight donors with HBsAg-positive and 279 donors with HBsAg-negative were transplanted and enrolled in this study. PSM analysis were used to eliminate selection bias. Perioperative data and survival were collected and analyzed. Results: PSM generated 44 patient pairs. When comparing intra- and post-operative data, no significant difference was found between groups (P > 0.05). Patients with a HBsAg-positive donor had significantly worse progression-free survival (1-year: 65.9% vs. 90.9%; 3-year: 18.1% vs. 70.4%, P = 0.0060) and overall survival (1-year: 84.1% and 95.4%; 3-year: 27.2% vs. 79.5%, P = 0.0039). In multivariate analysis, donor HBsAg-positivity was an independent risk factor for survival and occurrence (P = 0.005 and 0.025, respectively). Conclusion: In conclusion, with adequate antiviral prophylaxis and treatment, utilization of HBsAg positive liver grafts did not increase the incidence of early-stage complications. However, patient with an HBsAg-positive graft had poorer progression-free survival and overall survival.
RESUMO
BACKGROUND: Ischemia-free liver transplantation (IFLT) has been innovated to avoid graft ischemia during organ procurement, preservation, and implantation. However, the metabolism activity of the donor livers between in the in situ and ex situ normothermic machine perfusion (NMP) conditions, and between standard criteria donor and extend criteria donor remains unknown. METHODS: During IFLT, plasma samples were collected both at the portal vein and hepatic vein of the donor livers in situ during procurement and ex situ during NMP. An ultra-high performance liquid chromatography-mass spectrometry was conducted to investigate the common and distinct intraliver metabolite exchange. RESULTS: Profound cysteine and methionine metabolism, and aminoacyl-tRNA biosynthesis were found in both in situ and ex situ conditions. However, obvious D-arginine and D-ornithine metabolism, arginine and proline metabolism were only found in the in situ condition. The suppressed activities of the urea cycle pathway during ex situ condition were confirmed in an RNA expression level. In addition, compared with extend criteria donor group, standard criteria donor group had more active intraliver metabolite exchange in metabonomics level. Furthermore, we found that the relative concentration of p-cresol, allocystathionine, L-prolyl-L-proline in the ex situ group was strongly correlated with peak alanine aminotransferase and aspartate aminotransferase at postoperative days 1-7. CONCLUSIONS: In the current study, we show the common and distinct metabolism activities during IFLT. These findings might provide insights on how to modify the design of NMP device, improve the perfusate components, and redefine the criteria of graft viability.
Assuntos
Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Doadores Vivos , Perfusão/métodos , Fígado/irrigação sanguíneaRESUMO
A study on the value accounting of forest carbon sink services can promote the rapid development of the carbon sink market and help better understand the impact of forest carbon sinks on climate change and economic development. However, few studies have evaluated the value of China's current forest carbon sink services. Based on research on carbon peak and carbon neutrality, according to the characteristics of China's forest ecosystems and forest resource inventory data, the stock volume method was used to measure the amount and value of forest carbon sinks in China in 2009-2013 and 2014-2018. The results showed that: (1) the physical amount of forest carbon aggregates in China increased from 2009 to 2013 and from 2014 to 2018. The carbon storage of natural and plantation forests both showed an upward trend. Among them, the growth rate of the carbon storage of plantation forests was higher than that of natural forests. (2) The state, adjoint, and coupling equations of forest carbon sinks were employed to ascertain the best price for China's forest carbon sinks in 2020. The results showed that the price of China's forest carbon sinks was slightly higher than the internationally accepted carbon sink price, reflecting that the changes in the value of China's forest carbon sinks and international carbon sinks were roughly the same. (3) We obtained an appropriate accounting model for China's forest carbon sinks. (4) The value of China's forest carbon sinks increased from 2009 to 2013 and from 2014 to 2018. Although the price of carbon sinks has declined, the overall forest resource stock has increased, especially in plantation forests. The increase in the value of carbon sinks was as high as 24.7%, resulting in an overall increase in the value of forest carbon sinks, which was also in line with the physical amount of forest carbon sinks. The measurement conclusions were consistent. Several key points to note based on these findings are as follows: (1) China's current forest carbon sink transactions are all project-level certified emission reduction transactions, and diversified non-market means should be constructed to comprehensively promote carbon sink transactions. (2) China's current carbon sink transactions are mainly clean development mechanism projects, with few transactions between enterprises, and the carbon trading market situation is not optimistic. (3) The key to effective forest carbon sequestration trading is the accurate accounting of forest carbon storage and carbon sequestration value. Thus, it is of great significance to establish a forest carbon sequestration measurement method that is economical, simple, and accurate. (4) The physical amount and value of carbon sequestration of China's forest resources are rising, and the contribution rate is increasing year by year. However, there is still a gap in per capita forest area and storage compared with those in other countries worldwide. Thus, China must be vigilant in times of peace and further strengthen the protection and construction of forest resources.
Assuntos
Sequestro de Carbono , Ecossistema , Carbono/análise , China , Florestas , ÁrvoresRESUMO
BACKGROUND: Traditional liver transplant strategies with cold preservation usually result in ischemia-reperfusion injury (IRI) to the donor liver. Regular normothermic machine perfusion (NMP) donor livers suffer IRI twice. Here, we aimed to introduce a novel technique called continuous NMP without recooling to avoid a second IRI and its application in livers from extended criteria donors. METHODS: Seven donor livers transplanted following continuous NMP without recooling, 7 donor livers transplanted following standard NMP, and 14 livers under static cold storage (SCS) were included in this study. Perioperative outcomes were recorded and analyzed between groups. RESULTS: During the NMP without a recooling procedure, all livers cleared lactate quickly to normal levels in a median time of 100 min (interquartile range, 60-180) and remained stable until the end of perfusion. In the NMP without recooling and standard NMP groups, posttransplant peak aspartate aminotransferase and alanine aminotransferase levels were both significantly lower than those in the SCS group (P = 0.0015 and 0.016, respectively). The occurrence rate of early allograft dysfunction was significantly lower in the NMP without recooling group than in the SCS group (P = 0.022), whereas there was no difference in the NMP group with or without recooling (P = 0.462). CONCLUSIONS: Our pilot study revealed a novel technique designed to avoid secondary IRI. This novel technique is shown to have at least a comparable effect on the standard NMP, although more data are needed to show its superiority in the future.