Research and Innovation in Organ Donation: Recommendations From an International Consensus Forum.

This report provides recommendations from the Research and Innovation domain as part of the International Donation and Transplantation Legislative and Policy Forum (hereafter the Forum) to provide expert guidance on the structure of an ideal organ and tissue donation and transplantation system. The recommendations focus on deceased donation research and are intended for clinicians, investigators, decision-makers, and patient, family, and donor (PFD) partners involved in the field. Methods: We identified topics impacting donation research through consensus using nominal group technique. Members performed narrative reviews and synthesized current knowledge on each topic, which included academic articles, policy documents, and gray literature. Using the nominal group technique, committee members discussed significant findings, which provided evidence for our recommendations. The Forum's scientific committee then vetted recommendations. Results: We developed 16 recommendations in 3 key areas to provide stakeholders guidance in developing a robust deceased donor research framework. These include PFD and public involvement in research; donor, surrogate, and recipient consent within a research ethics framework; and data management. We highlight the importance of PFD and public partner involvement in research, we define the minimum ethical requirements for the protection of donors and recipients of both target and nontarget organ recipients, and we recommend the creation of a centrally administered donor research oversight committee, a single specialist institutional review board, and a research oversight body to facilitate coordination and ethical oversight of organ donor intervention research. Conclusions: Our recommendations provide a roadmap for developing and implementing an ethical deceased donation research framework that continually builds public trust. Although these recommendations can be applied to jurisdictions developing or reforming their organ and tissue donation and transplantation system, stakeholders are encouraged to collaborate and respond to their specific jurisdictional needs related to organ and tissue shortages.

Chinese Efforts to Pursue Effective Communication With Family of Potential Organ and Tissue Donor.

Within the last decade, deceased organ donation and transplantation in China have made great progress, but there is still much room for improvement. Inefficient communication with the family of potential organ and tissue donors is one of the major reasons for donor loss. In this study, the current progress of the deceased organ donation program in China was summarized, with a particular focus on the analysis of problems and solutions for achieving best practices in communication with the family of potential organ and tissue donors. This paper is in compliance with the Helsinki Congress and the Declaration of Istanbul.

Understanding public opinion regarding organ donation in China: A social media content analysis.

Organ donation provides a life-saving opportunity for patients with organ failure. China, like most countries, is faced with organ shortages. Understanding public opinion regarding organ donation in China is critical to ensure an increased donation rate. Our study explored public concerns and attitudes toward organ donation, factors involved, and how the public pays attention to organ donation. Sixteen million users' public information (i.e. gender, age, and geographic information) and posts from January 2017 to December 2017 were collected from Weibo, a social media platform. Of these, 1755 posts related to organ donation were included in the analysis. We categorized the posts and coded the users' attitudes toward organ donation and the associations between the demographics. The most popular posts mentioning organ donation were "publicly expressing the willingness to donate organs." Furthermore, 87.62% of posts exhibited a positive attitude toward organ donation, whereas only 7.44% exhibited a negative attitude. Most positive posts were "saluting the organ donors," and most negative posts involved "fear of the family's passive medical decision." There was no significant gender difference in the users' attitudes, but older people generally had a more negative attitude. Users with negative attitudes mainly distrust the medical system and are worried that the donated organs may be used in improper trading. Social media may be an important channel for promoting organ donation activities, and it is important to popularize scientific knowledge related to organ donation in order to eliminate the public's misunderstanding of organ donation and transplantation.

Characterizing Media Content and Effects of Organ Donation on a Social Media Platform: Content Analysis.

BACKGROUND: The lack of organ donors has become a barrier for the development of organ transplantation programs, and many countries are currently facing a severe shortage of deceased organs. Media campaigns on social media have the potential to promote organ donation. However, little is known about what kind of media content is the most appropriate for this purpose. OBJECTIVE: This study aimed to analyze media posts regarding organ donation on Weibo, a social media platform, and to identify the media themes that are most advantageous in promoting public awareness and attitudes concerning organ donation. METHODS: Based on 16 million social media users' posts randomly extracted from January 1 to December 31, 2017, 1507 reposts of 141 distinct media posts relevant to organ donation were found. We analyzed the media posts' themes and examined their effects in promoting public awareness about organ donation by comparing the number of reposts and comments they prompted. The themes' impact on attitude toward organ donation was gauged using the comments indicating support and intentions for organ donation. RESULTS: Overall, 5 major themes were identified from the media posts, among which "organ donation behaviors" constituted the highest proportion (58/141, 41.13%). However, themes of "statistical descriptions of organ donation" and "meaningfulness of donation" were the most influential in promoting awareness on organ donation: approximately 3 of 10 commenters for the former theme and 2 of 10 commenters for the latter expressed intentions to become organ donors. These two themes, along with "meaningfulness of organ donation for society," a subtheme of "meaningfulness of donation," were the most effective for evoking support and intentions for donation. CONCLUSIONS: A discrepancy was revealed between the media themes that were the most salient on the media agenda and those that were the most effective in increasing organ donation awareness and intentions on social media. These findings provide guidance for campaigns on organ donation. The results also suggest the potential of campaigns on social media for promoting prosocial health behaviors and highlight the importance of strategic message design for serving this goal.

Smaller grafts do not imply early recurrence in recipients transplanted for hepatocellular carcinoma: A Chinese experience.

Liver graft size has long been a critical issue in adult-to-adult living donor liver transplantation (LDLT). We analyzed China Liver Transplant Registry data (January 2007-December 2009), identifying 295 patients who underwent LDLT for hepatocellular carcinoma (HCC). The recipients were divided into two groups: A, graft-to-recipient body weight ratio (GRWR) ≤ 0.8% (n = 56); B, GRWR > 0.8% (n = 239). We evaluated donor, recipient, and operative factors and analyzed survival outcome and the risk factors affecting overall and recurrence survival. As a result, the overall survival rates of group B were significantly higher than that of group A (p = 0.009); the corresponding tumor-free survival rates did not differ significantly (p = 0.133). The overall survival rates among the 151 recipients who met the Hangzhou criteria did not differ significantly (p = 0.953), nor did the corresponding tumor-free survival rates (p = 0.893). Multivariate analysis determined that GRWR was a significant risk factor for poor survival but not for early recurrence. In conclusion, small grafts may predict poorer survival outcome but do not indicate earlier HCC recurrence in recipients transplanted for HCC, and survival outcome with smaller grafts is merely acceptable in selected recipients.

Liver transplantation for hepatocellular carcinoma beyond the Milan criteria.

OBJECTIVE: Liver transplantation is an optimal radical therapy for selected patients with hepatocellular carcinoma. The stringent organ allocation system driven by the Milan criteria has been challenged by alternative sets of expanded criteria. Careful analysis is needed to prove that the Milan criteria can be expanded safely and effectively. DESIGN: This study collectively reviewed 6012 patients of hepatocellular carcinoma from the China Liver Transplant Registry. Expanded criteria were evaluated to characterise an optimised expansion with acceptable outcomes beyond the Milan criteria. RESULTS: Compared with the Milan criteria, Valencia, University of California, San Francisco, University Clinic of Navarra and Hangzhou criteria provided an expansion of 12.4%, 16.3%, 19.6%, and 51.5%, respectively. The post-transplant survivals of patients fulfilling the expanded criteria were comparable to that of the Milan criteria. The analysis of net reclassification improvement and area under the receiver operating characteristic curves showed an excellent efficiency in recurrence prediction for the expanded criteria compared with the Milan criteria. In patients exceeding Milan but fulfilling the Hangzhou criteria (N=1352), α-fetoprotein (AFP) >100 ng/mL and tumour burden>8 cm were the only two independent prognostic factors (p<0.001). Accordingly, the Hangzhou criteria were stratified as type A (tumour burden ≤8 cm, or tumour burden >8 cm but AFP≤100 ng/mL) and type B (tumour burden >8 cm but AFP between 100 and 400 ng/mL). Type A showed significantly higher 5-year tumour-free survival rates compared with type B (p<0.001). CONCLUSIONS: The Milan criteria can be expanded safely and effectively. The prognostic stratification system based on the Hangzhou criteria serves as a hierarchy of transplant candidates for hepatocellular carcinoma.

Protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats.

OBJECTIVE: To observe the protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats. METHODS: A total of 60 Wister rats were included in the study and divided into control group (n = 10), model group (n = 25) and treatment group (n = 25). Model group and treatment group received intraperitoneal injection of endotoxin (ET) to establish acute renal injury models while the control group only received daily intraperitoneal injection of normal saline 1 mL. Five rats were taken out of model group and treatment group respectively at 1 h (T1), 6 h (T2), 12 h (T3), 24 h (T4) and 48 h (T5), for intraperitoneal injection of ET 30 mg/kg. Treatment group received intraperitoneal injection of fasudil hydrochloride 30 mg/kg 1 h before injection of ET. For three groups, 5 mL blood samples were collected from postcava for determination of serum creatinine and urea nitrogen levels at different time points. Concentrations of serum tumor necrosis factor α and ET-1 were determined by using ELISA. The renal pathologic changes were observed under the microscope. RESULTS: Serum creatinine levels in both model group and treatment group were significantly higher than control group at T2-T5 (P < 0.05) while the levels in treatment group were significantly lower than control group at T3-T5 (P < 0.05). At T2-T5, blood urea nitrogen levels in model group and treatment group were significantly higher than control group (P < 0.05) while the levels in treatment group were significantly lower than model group at T3-T5 (P < 0.05). Concentrations of serum tumor necrosis factor α in model group and treatment group were significantly higher than control group at T1-T5 (P < 0.05) while the levels in treatment group were significantly lower than model group at T1-T5 (P < 0.05). Serum ET-1 concentrations in model group and treatment group were significantly higher than control group at T1-T5 (P < 0.05) while the levels in treatment group at T1-T4 were significantly lower than model group (P < 0.05). Rats in control group showed no swelling or hyperemia in kidney cells but normal structure and normally arranged renal tubular epithelial cells. Obvious injury was observed in model group at T3 and renal tubular epithelial cells in disorder and at swelling condition, hyperemia and angiectasis in glomerulus, degenerative opacities and vacuolar degeneration, and maximized injury were observed at T4. Injury in renal tissue in treatment group was significantly milder than model group. CONCLUSIONS: Fasudil hydrochloride has the significantly protective effect against acute renal injury in septicopyemia rats.

Luteolin-induced protection of H2O2-induced apoptosis in PC12 cells and the associated pathway.

Increasing evidence has indicated that the generation of reactive oxygen species (ROS) contributes to H2O2­induced nerve injury. This may result in oxidative stress that leads to cell damage or death. Dietary or pharmaceutical augmentation of the endogenous antioxidant defense capacity is a potential means by which to prevent ROS­induced damage. The aim of the current study was to investigate the effect of luteolin on H2O2­induced cell apoptosis in cultured rat pheochromocytoma cells (PC12 cells) and to investigate the role of the phosphatidylinositol­3­kinase (PI3K)/protein kinase B (Akt) pathway on H2O2­induced apoptosis. The results demonstrated that luteolin was able to inhibit the reduction in cell viability induced by H2O2. In addition, luteolin reduced ROS generation and lactate dehydrogenase release in H2O2­treated PC12 cells. The levels of superoxide dismutase and glutathione peroxidase activity were increased following treatment with luteolin, however malondialdehyde levels were observed to be reduced. Additionally, luteolin increased the Bcl­2/Bax ratio and enhanced Akt phosphorylation. However, these alterations were attenuated by pretreatment with an inhibitor of the PI3K/Akt pathway. In conclusion, luteolin inhibited H2O2­induced apoptosis via reducing ROS levels and activating the PI3K/Akt pathway.

Liver transplantation in mainland China: the overview of CLTR 2011 annual scientific report.

China Liver Transplant Registry (CLTR) is the official national liver transplant registry in Mainland China that has been authorized by the National Health and Family Planning Commission of the People's Republic of China (NHFPC) and serves for both regulatory and scientific purposes. The CLTR 2011 annual scientific reports released national statistics describing current status of liver transplant (LT) in China. This article, as an accompanying document of CLTR 2011 annual scientific report, provides an overview of scientific results for LT in China. Up to December 2011, a total number of 20,877 LT performed during 1980-2011 in 81 certified transplant centers had been reported to CLTR. Of these donated livers, 92.63% were procured from deceased donors (N=19,338) and 7.37% were from living donors (N=1,539). In March 2010, the pilot project of the new deceased organ donation was initiated. From the initiation of the pilot program to the end of 2011, there were 115 LT (0.55% of all LT) using the liver grafts from Chinese categories donors. The recipient post-transplant survival had been significantly improved over years. The median post-transplant follow-up was 14.74 months, of which the longest follow-up time was 192.47 months. The 1-year, 3-year and 5-year cumulative survival rate for all recipients was 77.97%, 65.38% and 60.53%, respectively.

Major influence of renal function on hyperlipidemia after living donor liver transplantation.

AIM: To investigate the impact of renal and graft function on post-transplant hyperlipidemia (PTHL) in living donor liver transplantation (LDLT). METHODS: A total of 115 adult patients undergoing LDLT from January 2007 to May 2009 at a single center were enrolled. Data were collected and analyzed by the China Liver Transplant Registry retrospectively. PTHL was defined as serum triglycerides ≥ 150 mg/dL or serum cholesterol ≥ 200 mg/dL or the need for pharmacologic treatment at the sixth month after LDLT. Early renal dysfunction (ERD) was defined as serum creatinine ≥ 2 mg/dL and/or the need for renal replacement therapy in the first post-transplant week. RESULTS: In 115 eligible patients, the incidence of PTHL was 24.3%. Recipients with PTHL showed a higher incidence of post-transplant cardiovascular events compared to those without PTHL (17.9% vs 4.6%, P = 0.037). Serum creatinine showed significant positive correlations with total serum triglycerides, both at post-transplant month 1 and 3 (P < 0.01). Patients with ERD had much higher pre-transplant serum creatinine levels (P < 0.001) and longer duration of pre-transplant renal insufficiency (P < 0.001) than those without ERD. Pre-transplant serum creatinine, graft-to-recipient weight ratio, graft volume/standard liver volume ratio, body mass index (BMI) and ERD were identified as risk factors for PTHL by univariate analysis. Furthermore, ERD [odds ratio (OR) = 9.593, P < 0.001] and BMI (OR = 6.358, P = 0.002) were identified as independent risk factors for PTHL by multivariate analysis. CONCLUSION: Renal function is closely associated with the development of PTHL in LDLT. Post-transplant renal dysfunction, which mainly results from pre-transplant renal insufficiency, contributes to PTHL.