Reactive Oxygen Species Responsive Multifunctional Fusion Extracellular Nanovesicles: Prospective Treatments for Acute Heart Transplant Rejection.

Heart transplantation offers life-saving treatment for patients with end-stage heart failure; however, ischemia-reperfusion injury (IRI) and subsequent immune responses remain significant challenges. Current therapies primarily target adaptive immunity, with limited options available for addressing IRI and innate immune activation. Although plant-derived vesicle-like nanoparticles show promise in managing diseases, their application in organ transplantation complications is unexplored. Here, this work develops a novel reactive oxygen species (ROS)-responsive multifunctional fusion extracellular nanovesicles carrying rapamycin (FNVs@RAPA) to address early IRI and Ly6C+Ly6G- inflammatory macrophage-mediated rejection in heart transplantation. The FNVs comprise Exocarpium Citri grandis-derived extracellular nanovesicles with anti-inflammatory and antioxidant properties, and mesenchymal stem cell membrane-derived nanovesicles expressing calreticulin with macrophage-targeting ability. A novel ROS-responsive bio-orthogonal chemistry approach facilitates the active targeting delivery of FNVs@RAPA to the heart graft site, effectively alleviating IRI and promoting the polarization of Ly6C+Ly6G- inflammatory macrophages toward an anti-inflammatory phenotype. Hence, FNVs@RAPA represents a promising therapeutic approach for mitigating early transplantation complications and immune rejection. The fusion-targeted delivery strategy offers superior heart graft site enrichment and macrophage-specific targeting, promising improved transplant outcomes.

Dihydroartemisinin inhibits follicular helper T and B cells: implications for systemic lupus erythematosus treatment.

Systemic lupus erythematosus (SLE) is a common autoimmune disease, and its pathogenesis mainly involves the aberrant activation of B cells through follicular helper T (Tfh) cells to produce pathogenic antibodies, which requires more effective and safe treatment methods. Dihydroartemisinin (DHA) is the main active ingredient of artemisinin and has immunosuppressive effects. In this study, in vitro experiments confirmed that DHA inhibited Tfh cell induction and weakened its auxiliary function in B cell differentiation; furthermore, DHA directly inhibited B cell activation, differentiation, and antibody production. Furthermore, a mouse model of SLE was established, and we confirmed that DHA significantly reduced the symptoms of SLE and lupus nephritis, and decreased serum immunoglobulin (Ig)G, IgM, IgA, and anti-dsDNA levels. Moreover, DHA reduced the frequencies of total Tfh cells, activated Tfh cells, and B cell lymphoma 6, and interleukin (IL)-21 levels in Tfh cells from the spleen and lymph nodes, as well as the levels of B cells, germinal center B cells, and plasma cells in the spleen, lymph nodes, and kidneys. Additionally, DHA inhibited Tfh cells by blocking IL-2-inducible T cell kinase (ITK) signaling and its downstream nuclear factor (NF)-κB, nuclear factor of activated T cell, and activating protein-1 pathways, and directly inhibited B cells by blocking Bruton's tyrosine kinase (BTK) signaling and the downstream NF-κB and Myc pathways. Overall, our results demonstrated that DHA inhibited Tfh cells by blocking ITK signaling and also directly inhibited B cells by blocking BTK signaling. Therefore, reducing the production of pathogenic antibodies might effectively treat SLE.

The recent advancements in protein nanoparticles for immunotherapy.

In recent years, the advancement of nanoparticle-based immunotherapy has introduced an innovative strategy for combatting diseases. Compared with other types of nanoparticles, protein nanoparticles have obtained substantial attention owing to their remarkable biocompatibility, biodegradability, ease of modification, and finely designed spatial structures. Nature provides several protein nanoparticle platforms, including viral capsids, ferritin, and albumin, which hold significant potential for disease treatment. These naturally occurring protein nanoparticles not only serve as effective drug delivery platforms but also augment antigen delivery and targeting capabilities through techniques like genetic modification and covalent conjugation. Motivated by nature's originality and driven by progress in computational methodologies, scientists have crafted numerous protein nanoparticles with intricate assembly structures, showing significant potential in the development of multivalent vaccines. Consequently, both naturally occurring and de novo designed protein nanoparticles are anticipated to enhance the effectiveness of immunotherapy. This review consolidates the advancements in protein nanoparticles for immunotherapy across diseases including cancer and other diseases like influenza, pneumonia, and hepatitis.

Dynamic optimization of battery recycling e-platforms under non-equalizing supply and demand: Recycling price and service commissions.

With the rapid advancement of electric vehicles (EVs), the burgeoning increase in used power batteries necessitates the development of efficient battery recycling e-platforms. A key challenge in this field is the mismatch between supply and demand. In response, a dynamic optimization model is proposed to capture the non-equalizing supply-demand relationship and its linkage over continuous periods to enable dynamic simulations and predictions of transaction volume changes. Meanwhile, pricing and commission-setting strategies are optimized based on the objectives of maximizing social welfare and platform revenue. The result shows that due to the lower recycling volumes that result, increasing the recycling price usually increases platform revenues, exacerbates environmental costs, and leads to lower social welfare. Moreover, platform revenues are more sensitive to commission rates than social welfare, which is more vulnerable to recycling prices. Furthermore, prioritizing social welfare leads to a higher recycling volume compared to prioritizing revenue, but it also creates an imbalance between supply and demand, destabilizing the recycling market. With the dynamic pricing and commission strategies, this study enriches the literature in the third-party recycling mode for power batteries, offering a novel perspective that is more aligned with real-world operational conditions. Our findings help platforms clarify the impact of pricing and commission decisions on platform revenue and social welfare and thereby provide support for their decision optimization.

Increasing forest carbon sinks in cold and arid northeastern Tibetan Plateau.

Arid forest lands account for 6 % of the world's forest area, but their carbon density and carbon storage capacity have rarely been assessed. Forest inventories provide estimates of forest stock and biomass carbon density, improve our understanding of the carbon cycle, and help us develop sustainable forest management policies in the face of climate change. Here, we carried out three forest inventories at five-year intervals from 2006 to 2016 in 104 permanent sample plots covering the Qinghai spruce (Picea crassifolia) distribution in the north slope of Qilian Mountains, northeastern Tibetan Plateau. Results shows that mean biomasses for Qinghai spruce were 133.80, 144.89, and 157.01 Mg ha-1 while biomass carbon densities were 65.52, 70.92, and 76.88 Mg C ha-1, in 2006, 2011, and 2016, respectively. This shows an increase in the Qinghai spruce carbon density of 17.34 % from 2006 to 2016. Both the precipitation and temperature play crucial roles on the increase of aboveground carbon density. The average carbon densities were different among forests with different ages and were higher for older forests. Our results show that the carbon sequestration rate for Qinghai spruce in the Qilian Mountains is significantly higher than the average rates of national forest parks in China, suggesting that this spruce forest has the potential to sequester a significant amount of carbon despite the general harsh growing conditions of cold and arid ecoregions. Our findings provide important insights that are helpful for the assessment of forest carbon for cold and arid lands.

Preventative effect of TSPO ligands on mixed antibody-mediated rejection through a Mitochondria-mediated metabolic disorder.

BACKGROUND: Immune-mediated rejection was the major cause of graft dysfunction. Although the advances in immunosuppressive agents have markedly reduced the incidence of T-cell-mediated rejection after transplantation. However, the incidence of antibody-mediated rejection (AMR) remains high. Donor-specific antibodies (DSAs) were considered the major mediators of allograft loss. Previously, we showed that treatment with 18-kDa translocator protein (TSPO) ligands inhibited the differentiation and effector functions of T cells and reduced the rejection observed after allogeneic skin transplantation in mice. This study we further investigate the effect of TSPO ligands on B cells and DSAs production in the recipients of mixed-AMR model. METHODS: In vitro, we explored the effect of treatment with TSPO ligands on the activation, proliferation, and antibody production of B cells. Further, we established a heart-transplantation mixed-AMR model in rats. This model was treated with the TSPO ligands, FGIN1-27 or Ro5-4864, to investigate the role of ligands in preventing transplant rejection and DSAs production in vivo. As TSPO was the mitochondrial membrane transporters, we then investigated the TSPO ligands effect on mitochondrial-related metabolic ability of B cells as well as expression of downstream proteins. RESULTS: In vitro studies, treatment with TSPO ligands inhibited the differentiation of B cells into CD138+CD27+ plasma cells; reduced antibodies, IgG and IgM, secretion of B cells; and suppressed the B cell activation and proliferation. In the mixed-AMR rat model, treatment with FGIN1-27 or Ro5-4864 attenuated DSA-mediated cardiac-allograft injury, prolonged graft survival, and reduced the numbers of B cells, including IgG+ secreting B cells, T cells and macrophages infiltrating in grafts. For the further mechanism exploration, treatment with TSPO ligands inhibited the metabolic ability of B cells by downregulating expression of pyruvate dehydrogenase kinase 1 and proteins in complexes I, II, and IV of the electron transport chain. CONCLUSIONS: We clarified the mechanism of action of TSPO ligands on B-cell functions and provided new ideas and drug targets for the clinical treatment of postoperative AMR.

Ex vivo anchored PD-L1 functionally prevent in vivo renal allograft rejection.

Organ transplantation is the optimal treatment for patients with end-stage diseases. T cell activation is a major contributing factor toward the trigger of rejection. Induction therapy with T cell depleting agent is a common option but increases the risk of severe systemic infections. The ideal therapy should precisely target the allograft. Here, we developed a membrane-anchored-protein PD-L1 (map-PD-L1), which effectively anchored onto the surface of rat glomerular endothelial cells (rgEC). The expression of PD-L1 increased directly with map-PD-L1 concentration and incubation time. Moreover, map-PD-L1 was even stably anchored to rgEC at low temperature. Map-PD-L1 could bind to PD-1 and significantly promote T cell apoptosis and inhibited T cell activation. Using kidney transplantation models, we found that ex vivo perfusion of donor kidneys with map-PD-L1 significantly protected grafts against acute injury without using any immunosuppressant. We found map-PD-L1 could reduce T cell graft infiltration and increase intragraft Treg infiltration, suggesting a long-term effect in allograft protection. More importantly, modifying donor organs in vitro was not only safe, but also significantly reduced the side effects of systemic application. Our results suggested that ex vivo perfusion of donor organ with map-PD-L1 might provide a viable clinical option for organ-targeted induction therapy in organ transplantation.

Exploring the Spatiotemporal Evolution and Sustainable Driving Factors of Information Flow Network: A Public Search Attention Perspective.

The promotion of information flow reinforces the interactive cooperation and evolutionary process among cities. In the information age, public online search is a typical behavior of Internet society, which is the key to information flow generation and agglomeration. In this study, we attempt to explore the evolutionary characteristics of intercity networks driven by public online social behavior in the information age and construct an information flow network (IFN) from the perspective of public search attention. We also explore the evolution of the IFN in terms of the whole network, node hierarchy, and subgroup aggregation. Meanwhile, we also discuss the impact of the sustainable driving factors on the IFN. Finally, an empirical study was conducted in Guanzhong Plain Urban Agglomeration (GPUA). Our results show that: (1) the information flow in GPUA fluctuating upward in the early study period and gradually decreasing in the later study period. However, the agglomeration degree of information flow in the urban agglomeration continues to increase. (2) The hierarchical structure of urban nodes in GPUA presents a trend of "high in the middle and low on both sides", and the formation of subgroups is closely related to geographic location. (3) The driving factors all impacting the IFN include public ecology, resource investment, information infrastructure, and economic foundation. This study provides theoretical and practical support for exploring the intercity network and promotes the sustainable urban development.

Corrigendum: Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model.

[This corrects the article DOI: 10.3389/fimmu.2021.778359.].

Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model.

Acute antibody-mediated rejection (AAMR) is an important cause of cardiac allograft dysfunction, and more effective strategies need to be explored to improve allograft prognosis. Interleukin (IL)-6/IL-6R signaling plays a key role in the activation of immune cells including B cells, T cells and macrophages, which participate in the progression of AAMR. In this study, we investigated the effect of IL-6/IL-6R signaling blockade on the prevention of AAMR in a mouse model. We established a mouse model of AAMR for cardiac transplantation via presensitization of skin grafts and addition of cyclosporin A, and sequentially analyzed its features. Tocilizumab, anti-IL-6R antibody, and recipient IL-6 knockout were used to block IL-6/IL-6R signaling. We demonstrated that blockade of IL-6/IL-6R signaling significantly attenuated allograft injury and improved survival. Further mechanistic research revealed that signaling blockade decreased B cells in circulation, spleens, and allografts, thus inhibiting donor-specific antibody production and complement activation. Moreover, macrophage, T cell, and pro-inflammatory cytokine infiltration in allografts was also reduced. Collectively, we provided a highly practical mouse model of AAMR and demonstrated that blockade of IL-6/IL-6R signaling markedly alleviated AAMR, which is expected to provide a superior option for the treatment of AAMR in clinic.

Plasma Macrophage Migration Inhibitory Factor Predicts Graft Function Following Kidney Transplantation: A Prospective Cohort Study.

Background: Delayed graft function (DGF) is a common complication after kidney transplantation (KT) with a poor clinical outcome. There are no accurate biomarkers for the early prediction of DGF. Macrophage migration inhibitory factor (MIF) release during surgery plays a key role in protecting the kidney, and may be a potential biomarker for predicting post-transplant renal allograft recovery. Methods: Recipients who underwent KT between July 2020 and December 2020 were enrolled in the study. Plasma MIF levels were tested in recipients at different time points, and the correlation between plasma MIF and DGF in recipients was evaluated. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000035596). Results: Intraoperative MIF levels were different between immediate, slowed, and delayed graft function groups (7.26 vs. 6.49 and 5.59, P < 0.001). Plasma MIF was an independent protective factor of DGF (odds ratio = 0.447, 95% confidence interval [CI] 0.264-0.754, P = 0.003). Combining plasma MIF level and donor terminal serum creatinine provided the best predictive power for DGF (0.872; 95%CI 0.795-0.949). Furthermore, plasma MIF was significantly associated with allograft function at 1-month post-transplant (R 2 = 0.42, P < 0.001). Conclusion: Intraoperative MIF, as an independent protective factor for DGF, has excellent diagnostic performance for predicting DGF and is worthy of further exploration.

Donor plasma mitochondrial DNA is associated with antibody-mediated rejection in renal allograft recipients.

We previously showed that donor plasma mitochondrial DNA (dmtDNA) levels were correlated with renal allograft function. The aim of the current study was to determine whether dmtDNA levels are associated with the occurrence of antibody-mediated rejection (ABMR). This is a retrospective open cohort study comprised of 167 donors and 323 recipients enrolled from January 2015 to December 2017. We quantified the mtDNA level present in donor plasma using quantitative real-time polymerase chain reaction. The average plasma dmtDNA level in the acute rejection (AR) group was higher than that of the control group (0.156 versus 0.075, p<0.001). Multivariate logistic regression analysis showed that dmtDNA levels were also significantly associated with AR (OR=1.588, 95% CI 1.337-4.561, p<0.001). When the dmtDNA level was >0.156, the probability of AR was 62.9%. The plasma dmtDNA level in the ABMR group was significantly higher than that of the T cell-mediated rejection group (0.185 versus 0.099, p=0.032). The area under the receiver operating characteristic curve of dmtDNA for prediction of ABMR was as high as 0.910 (95% CI 0.843-0.977). We demonstrated that plasma dmtDNA was an independent risk factor for ABMR, which is valuable in organ evaluation. dmtDNA level is a possible first predictive marker for ABMR.

Triptolide Attenuates Transplant Vasculopathy Through Multiple Pathways.

Transplant vasculopathy (TV), a hallmark of chronic allograft rejection, is the primary cause of allograft loss after organ transplantation. Because multiple mechanisms are involved in TV pathogenesis, effective therapy for it remains elusive. Here, we identify the role of triptolide, which has a wide spectrum of immuno-suppressive activities, in inhibiting TV development. Murine aortic transplants models were constructed and divided into triptolide-treated and untreated groups. We found that triptolide significantly alleviated intima thickening of allografts by inhibiting multiple pathways. Triptolide significantly reduced infiltration of T lymphocytes and macrophages and inhibited the levels of pro-inflammatory (TNF-α, IL-2, and IL-6) and pro-fibrotic factors (TGF-ß, α-SMA, and MMP-9) in the graft. Additionally, triptolide significantly decreased the numbers of IFN-γ-producing T lymphocytes, as well as the expression of IFN-γ and IFN-γ-inducing factor (CXCL9 and CXCL10) in recipient. Moreover, triptolide decreased the numbers of B lymphocytes and plasma cells, as well as the levels of donor specific antibodies (DSAs) in recipient. Furthermore, triptolide not only inhibited vascular smooth muscle cell (VSMC) viability and promoted VSMC apoptosis but also significantly inhibited VSMC migration in vitro. These results emphasize the efficacy of triptolide in inhibiting TV development and provide a basis for developing new treatments to prevent TV-related complications and improve the long-term survival of transplant recipients.

The Influence of Continuous Improvement of Public Car-Sharing Platforms on Passenger Loyalty: A Mediation and Moderation Analysis.

Public car-sharing is a growing business model that contributes to sustainable transportation and urban development. The continuous improvement of public car-sharing platform to garner passenger loyalty is vital for a car-sharing platform's success. This study applied perceived value theory, trust theory, and transaction cost theory to construct a structural equation model in order to explain passenger loyalty. Data from 755 surveys were collected using stratified sampling in mainland China. The estimated results of the theoretical model show that the relationship between continuous improvement and passenger loyalty is mediated by passenger perceived value, passenger trust, and transaction costs. Consequently, a multi-group analysis is conducted to analyze the moderation effects of passenger's license and car-sharing experience on the theoretical model. The results show that some of the path coefficients are significantly different between these sub-groups. This indicates that platforms should provide differentiate services for passengers based on the purpose of using car-sharing and usage experience. This study provides new theoretical insights into understanding passenger loyalty with respect to public car-sharing and provides policy recommendations for the sustainable development of public car-sharing.

Delayed graft function is correlated with graft loss in recipients of expanded-criteria rather than standard-criteria donor kidneys: a retrospective, multicenter, observation cohort study.

BACKGROUND: Although the use of expanded-criteria donors (ECDs) alleviates the problem of organ shortage, it significantly increases the incidence of delayed graft function (DGF). DGF is a common complication after kidney transplantation; however, the effect of DGF on graft loss is uncertain based on the published literature. Hence, the aim of this study was to determine the relationship between DGF and allograft survival. METHODS: We conducted a retrospective, multicenter, observation cohort study. A total of 284 deceased donors and 541 recipients between February 2012 and March 2017 were included. We used logistic regression analysis to verify the association between clinical parameters and DGF, and Cox proportional hazards models were applied to quantify the hazard ratios of DGF for kidney graft loss. RESULTS: Among the 284 deceased donors, 65 (22.8%) donors were ECD. Of the 541 recipients, 107 (19.8%) recipients developed DGF, and this rate was higher with ECD kidneys than with standard-criteria donor (SCD) kidneys (29.2% vs. 17.1%; P = 0.003). The 5-year graft survival rate was not significantly different between SCD kidney recipients with and without DGF (95.8% vs. 95.4%; P = 0.580). However, there was a significant difference between ECD kidney recipients with and without DGF (71.4% vs. 97.6%; P = 0.001), and the adjusted hazard ratio (HR) for graft loss for recipients with DGF was 1.885 (95% confidence interval [CI] = 1.305-7.630; P = 0.024). Results showed that induction therapy with anti-thymocyte globulin was protective against DGF (odds ratio = 0.359; 95% CI = 0.197-0.652; P = 0.001) with all donor kidneys and a protective factor for graft survival (HR = 0.308; 95% CI = 0.130-0.728; P = 0.007) with ECD kidneys. CONCLUSION: DGF is an independent risk factor for graft survival in recipients with ECD kidneys, but not SCD kidneys.

Donor Plasma Mitochondrial DNA Is Correlated with Posttransplant Renal Allograft Function.

BACKGROUND: The lack of accurate biomarkers makes it difficult to determine whether organs are suitable for transplantation. Mitochondrial DNA (mtDNA) correlates with tissue damage and kidney disease, making it a potential biomarker in organ evaluation. METHODS: Donors who had experienced cardiac death and successfully donated their kidneys between January 2015 and May 2017 were included this study. We detected the level of mtDNA in the plasma of the donor using quantitative real-time polymerase chain reaction and then statistically analyzed the relationship between the level of mtDNA and the delayed graft function (DGF) of the recipient. RESULTS: The incidence of DGF or slowed graft function (SGF) increased by 4 times (68% versus 16%, P < 0.001) when the donor mtDNA (dmtDNA) level was >0.114. When dmtDNA levels were >0.243, DGF and primary nonfunction were approximately 100% and 44%, respectively. Moreover, dmtDNA was an independent risk factor for slowed graft function and DGF. A prediction model for DGF based on dmtDNA achieved an area under the receiver operating characteristic curve for a prediction score as high as 0.930 (95% confidence interval 0.856-1.000), and the validation cohort results showed that the sensitivity and specificity of the model were 100% and 78%, respectively. dmtDNA levels were correlated with 6-month allograft function (R=0.332, P < 0.001) and 1-year graft survival (79% versus 99%, P < 0.001). CONCLUSIONS: We conclusively demonstrated that plasma dmtDNA was an independent risk factor for DGF, which is valuable in organ evaluation. dmtDNA is a possible first predictive marker for primary nonfunction and worth further evaluation.

Cascading Failures and Vulnerability Evolution in Bus⁻Metro Complex Bilayer Networks under Rainstorm Weather Conditions.

In recent years, the frequent occurrence of rainstorms has seriously affected urban⁻public transport systems. In this study, we examined the impact of rainstorms on the vulnerability of urban⁻public transport systems consisting of both ground bus and metro systems, which was abstracted into an undirected weighted Bus⁻Metro complex bilayer network (Bus⁻Metro CBN) and the passenger volume was regarded as its weight. Through the changes in the node scale, network efficiency, and passenger volume in the maximal connected component of the Bus⁻Metro CBN, we constructed a vulnerability operator to quantitatively calculate the vulnerability of the Bus⁻Metro CBN. Then, the flow-based couple map lattices (CMLs) model was proposed to simulate cascading failure scenarios of the Bus⁻Metro CBN under rainstorm conditions, in which the rainstorm is introduced through a perturbation variable. The simulation results show that under the condition of passenger flow overload, the network may have a two-stage cascading failure process. The impact analysis shows that there is a rainstorm intensity threshold that causes the Bus⁻Metro CBN to collapse. Meanwhile, we obtained the optimal node and edge capacity through capacity analysis. In addition, our analysis implies that the vulnerability of the Bus⁻Metro CBN network in most scenarios is mainly caused by the degradation of network structure rather than the loss of passenger flow. The network coupling strength analysis results show that the node coupling strength has greater potential to reduce the vulnerability than edge coupling strength. This indicates that traffic managers should prioritize controlling the mutual influence between bus stops (or metro stations) to reduce the vulnerability of the Bus⁻Metro CBN more effectively.

Donation after brain death followed by circulatory death, a novel donation pattern, confers comparable renal allograft outcomes with donation after brain death.

BACKGROUND: Organ donation after brain death (DBD) is the standard strategy for organ transplantation; however, the concept of brain death is not universally accepted due to cultural beliefs and barriers amongst billions of people worldwide. Hence, a novel donation pattern has been established in China which outlines the concept of donation after brain death followed by circulatory death (DBCD). Differently from any current donation classification, this new concept is formulated based on combination of recognizing brain death and circulatory death. Should approval be gained for this definition and approach, DBCD will pave a novel donation option for billions of people who cannot accept DBD due to their cultural beliefs. METHODS: A multi-center, cohort study was conducted from February 2012 to December 2015. 523 kidney transplant recipients from four kidney transplant institutions were enrolled into the study, of which, 383 received kidneys from DBCD, and 140 from DBD. Graft and recipient survivals following transplantation were retrospectively analyzed. Postoperative complications including delayed graft function,, and acute rejection, were also analyzed for both groups. RESULTS: DBCD could achieve comparable graft and recipient survivals in comparison with DBD (Log-rank P = 0.32 and 0.86,respectively). One-year graft and recipient survivals were equal between DBCD and DBD groups (97.4% versus 97.9%, P = 0.10;98.4% versus 98.6%, P = 1.0, respectively). Furthermore, DBCD did not increase incidences of postoperative complications compared with DBD, including delayed graft function (19.3% versus 22.1%, P = 0.46) and acute rejection (9.1% versus 8.6%, P = 1.0). Additionally, antithymocyte globulin as induction therapy and shorter warm ischemia time decreased incidence of delayed graft function in DBCD group (16.8% on antithymocyte globulin versus 27.2% on basiliximab, P = 0.03; 16.7% on ≤18 min versus 26.7% on > 18 min group, P = 0.03). CONCLUSIONS: Kidney donation through DBCD achieves equally successful outcomes as DBD, and could provide a feasible path to graft availability for billions of people who face barriers to organ donation from DBD.

New Factors Predicting Delayed Graft Function: a Multi-Center Cohort Study of Kidney Donation After Brain Death Followed by Circulatory Death.

BACKGROUND/AIMS: Delayed graft function (DGF) is a common complication following kidney transplantation adversely affecting graft outcomes. Donation after brain death followed by circulatory death (DBCD), a novel donation pattern, is expected to correlate with high incidence of DGF. However, little information is available about factors associated with DGF in DBCD. METHODS: A total of 383 kidney transplants from DBCD donation in three institutions were enrolled. Associations of DGF with the clinical characteristics of recipients and donors were quantified. RESULTS: In this retrospective multi-center study, the incidence of DGF was 19.3%. Lower incidence of DGF was found in recipients for whom antithymocyte globulin was used for induction (p < 0.05), which was an independent protective factor against DGF (odds ratio [OR] = 0.48; 95% CI 0.27-0.86). Two novel explicative variables were recognized as independent risk factors, including use of vasoactive drugs (OR = 3.15; 95% CI 1.39-7.14) and cardiopulmonary resuscitation (OR = 2.51; 95% CI 1.05-6.00), which contributed significantly to increased risk of DGF (p < 0.05). Prolonged warm ischemia time (> 18 min; OR = 2.42; 95% CI 1.36-4.32), was also predictive of DGF in DBCD. A prediction model was developed and achieved an area under the curve of 0.89 in predicting DGF when combined with reported parameters. CONCLUSION: The novel factors, confirmed for the first time in our study, will help to improve risk prediction of DGF and to determine optimal interventions to prevent DGF in clinical practice.

Primitive neuroectodermal tumor of the kidney at the advanced stage: A case series of eight Chinese patients.

Primitive neuroectodermal tumor (PNET) rarely occurs as a primary renal neoplasm. Renal (r)PNET is a rare but aggressive neoplasm with poor prognosis; the majority of patients are diagnosed as advanced stage at presentation and face a worse prognosis than patients with localized disease. The present study describes the diagnosis and management of eight cases of rPNET at an advanced stage, who were treated at two institutions [Lingnan Hospital (branch of The Third Affiliated Hospital) and the Cancer Center of Sun Yat-sen University, Guangzhou], from December 2004 to January 2013. The clinical and pathological results of all patients were retrospectively obtained. Kaplan-Meier analysis was performed to estimate patient survival. The study cohort comprised five males and three females. Radical nephrectomy was performed in seven cases, while the remaining case only received needle biopsy of the tumor. Five cases received adjuvant chemotherapy, while three received no further treatment after surgery. Of note, one case received cytokine-induced killer (CIK) cell immunotherapy combined with surgery and chemotherapy. The overall median survival was 20 months with a 3-year survival rate of 25%. The overall survival of the four patients who received adjuvant chemotherapy following surgery was 36 months, compared with 10 months in the three patients without further treatment. The patient who received CIK cell immunotherapy survived for 20 months. Based on the observations of the present and previous studies, surgical excision and chemotherapy are recommended for treating rPNET at advanced stage. Furthermore, the present study was the first to report on CIK cell immunotherapy for a patient with rPNET, indicating that it may be a promising optional treatment. However, further studies are required to validate the benefit of CIK cells and to establish an appropriate immunotherapy protocol.