China Liver Transplant Registry, National Center for Healthcare Quality Management in Liver Transplant, National Quality Control Center for Donated Organ Procurement, National Clinical Research Center for Orthopedics, Sports Medicine Rehabilitation, Committee on Transplant Organ Quality Control, Branch of Organ Transplant Doctor, Chinese Medical Doctor Association, Organ Procurement and Allocation Working Committee of the China Hospital Association, National Trauma Medical Center Organ Protection Committee
The development of donation after citizen′s death and transplantation in China has progressed rapidly, with long-distance and prolonged organ transportation becoming a routine practice. Efficient, safe organ transportation and data management are critical to ensuring standardized transplant operations. In accordance with the Regulations on Human Organ Donation and Transplantation and to maximize the efficacy of the National Organ Transportation Green Channel initiative, standardize and enhance the quality of organ transportation at transplant centers, provincial levels, and nationwide, a group of leading experts has developed the Chinese Expert Consensus on Organ Transportation. By establishing standardized transport protocols, technical benchmarks, and digital management platforms, this consensus aims to further improve the efficiency and standardization of organ transfer operations, promoting high-quality development in China′s organ donation and transplantation.
To investigate the risk factors of lower extremity deep vein thrombosis(LEDVT) in liver transplant recipients, and to establish and validate a risk prediction model for LEDVT in recipients after liver transplantation.
Methods
A total of 336 recipients who underwent allogeneic orthotopic liver transplantation at the First Hospital of Jilin University from January 2020 to October 2023 were selected as the research subjects. The sample.split function was used to randomly divide the recipients into the modeling group (n=235) and the validation group (n=101) at a ratio of 7∶3. Through literature review, group discussion and clinical knowledge, the predictors of LEDVT in recipients after liver transplantation were determined. The group t test or Mann-Whitney U test was used for comparison of measurement data between groups. Comparison of counting data between groups was performed using the chi-square test or the Fisher exact probability method. Those predictors with P<0.05 in the univariate analysis were included in multivariate Logistic regression analysis to clarify the independent risk factors of LEDVT in recipients after liver transplantation.The nomogram was drawn using R (version 4.3.2) software, and a web-based calculator of the postoperative LEDVT risk prediction model for liver transplant recipients was developed on the shinyapps.io, and the area under the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and clinical decision curve were used to evaluate the discrimination, accuracy and clinical benefit of the LEDVT risk prediction model in liver transplant recipients. A P<0.05 was considered statistically significant.
Results
Among the 235 recipients in the modeling group, there were 49 cases in the LEDVT group and 186 cases in the non LEDVT group, with a LEDVT incidence rate of 20.8%(49/235). There were statistically significant differences in age, preoperative hepatic encephalopathy, daily living ability level, coagulation factor response time, postoperative AST, ALT, Na+ level, Ca2+ level, prothrombin time (PT), and international standardized ratio between the LEDVT group and non LEDVT group (Z=-3.552, -2.808, -2.567, -2.161, -2.297, -1.986, -3.815 and -2.395, χ2=13.822 and 36.213, all P<0.05).The results of multivariate Logistic regression analysis showed that the age (OR=1.048, 95%CI: 1.002-1.096), preoperative presence of hepatic encephalopathy (OR=2.484, 95%CI: 1.041-5.930), preoperative daily living ability (moderate dependence) (OR=5.266, 95%CI: 1.685-16.458), preoperative daily living ability (severe dependence) (OR=8.342, 95%CI: 1.748-39.802), postoperative Na+ level (OR=1.105, 95%CI: 1.001-1.220), and postoperative PT (OR=0.827, 95%CI: 0.737-0.928) were independent risk factors for postoperative LEDVT in liver transplant recipients (all P<0.05).The area under the ROC curve of the LEDVT risk prediction model of the modeling group and validation group were 0.811 (95%CI: 0.745-0.876) and 0.736 (95%CI: 0.615-0.856), respectively, the Hosmer Lemeshow test result showed χ2=5.166 and 10.378, all P<0.05. Good clinical benefits were shown both in the modeling group and validation group.
Conclusion
The risk prediction model established in this study has a good prediction effect and can provide a reference basis for clinical medical staff to evaluate the risk of postoperative LEDVT in liver transplant recipients.
To explore the immunosuppressive protocol and its effect in the gene-edited pig-rhesus monkey xenotransplantation experiment, and to provide a reference for the formulation of immunosuppressive protocol for xenogeneic organ transplantation.
Methods
Through preoperative matching experiments including phenotypic identification, complement-dependent cytotoxicity (CDC) experiment, and IgG and IgM binding experiments and so on, a double-gene knockout donor pig (lot number 4207) and a rhesus monkey (experimental animal registration number 382350) were selected as experimental animals. An ectopic heart transplantation surgery was chosen for transplantation. The immunosuppressive protocol was divided into the induction period and the maintenance period of immunosuppression.
Results
On December 16, 2023, the gene-edited pig-rhesus monkey ectopic heart transplantation surgery was performed successfully. The surgical process went on smoothly, and both the donor and recipient hearts successfully resumed beating. The general condition of the recipient was good after the surgery. On the 9th day after the surgery (T+ 9), due to ischemic necrosis of the left lower limb, a left lower limb amputation surgery was performed. The final survival time of the recipient monkey was 46 d. The possible cause of death was chronic rejection-induced decline in donor heart function and excessive dosage of anesthetic drugs administered to the recipient monkey before the myocardial tissue biopsy at T+ 46. After immunosuppression, the white blood cells and lymphocytes of the recipient were in a stable and low level, and the CDC reached steady state, settling below 4%. The flow cytometry analysis results of the recipient monkey showed that compared with 1 d before transplantation, the B cells with CD19 as the surface marker and T cells with CD3 as the surface marker were significantly reduced in T+ 46. The pathological examination results of the pig heart and rhesus monkey heart after the recipient′s death indicated that the staining of B cell surface marker CD19 and T cell surface marker CD3 was almost invisible, and the staining of complement activation marker C4D was relatively shallow; the staining frequency of macrophage surface marker CD68, IgG, and IgM was relatively higher.
Conclusion
The immunosuppressive protocol used in this experiment effectively inhibited hyperacute and acute rejection reactions, providing a feasible immunosuppressive protocol reference for future xenogeneic organ transplantation.
To investigate the superiority and key technical points of establishing a mouse cervical heterotopic heart transplantation model using the modified cuff technique.
Methods
The ascending aorta and pulmonary artery of the donor heart were anastomosed end-to-end to the recipient′s common carotid artery and external jugular vein, respectively, using a self-made tail-anchored cuff. Surgical success rate, operation time, and graft survival time were recorded. Pathological changes in the graft were assessed by HE staining. The experimental protocol included a pre-training phase and formal experimental phase, with mice in the formal phase divided into syngeneic control group and allogeneic transplant group. Survival curves were generated using the Kaplan-Meier method, and comparison was performed with the log-rank test. P<0.05 was considered statistically significant.
Results
A total of 181 cases of mouse heterotopic heart transplantation were performed in the training phase, with a surgical success rate of 22.1% (40/181) and gradual reduction in operation time. Reasons for graft failure included failure of donor-recipient vascular connection, rupture during recipient vessel dissection, sleeve eversion technique failure, venous congestion at the anastomosis site, and postoperative chronic hemorrhage. The recipient preparation time, donor heart harvesting time, heart transplantation time, total operation time were (25.2±1.0) min, (14.7±0.5) min, (22.0±1.1) min and (60.0±1.2) min, respectively. One mouse died of venous congestion-induced cardiac arrest one day after the operation in both the syngeneic control group and allogeneic transplant group, and one mouse died of arterial anastomosis leakage in the allogeneic transplant group, yielding a success rate of 85.7% (18/21). The median graft survival time was 7.0 (5.0-7.0) d in the allogeneic transplant group and >100 d in the syngeneic control group (excepting 1 dead mouse). There was statistical significance for the cumulative survival rate of graft between the two groups (χ2=14.83, P<0.05). Histopathology revealed no myocyte necrosis or inflammatory infiltration in the syngeneic control group, whereas the allogeneic transplant group exhibited extensive lymphocytic and mononuclear cells infiltration, myocardial edema, hemorrhagic necrosis, and microvascular occlusion, consistent with acute rejection.
Conclusion
The application of cuff with tail-fixated shank prevents vascular slippage and significantly reduces operative difficulty, thereby establishing itself as the preferred methodology for developing heterotopic cervical heart transplantation models in mice.
To early identify the potential brain death donors, a user-friendly and more accurate scale was constructed based on the Glasgow coma scale (GCS), brainstem reflex and spontaneous respiration assessment.
Methods
From January 1, 2021 to June 30, 2023, neurocritical patients in coma, admitted to the First Affiliated Hospital of SYSU and determined as brain death ultimately were retrospectively included as the retrospective group (n=175). Based on existing and previous studies of our center, the factors related to the progression to brain death of such patients were recorded, including GCS, brainstem reflexes (such as pupillary light reflex, corneal reflex, and vestibulo-ocular reflex), and spontaneous respiratory status. Brain death determination was according to the current criteria for brain death determination in China, and was completed by specialized doctors in our center. In the retrospective group, the relevant factors of the progression to brain death within 14 d after brain injury were screened, and were utilized to bulid the GCS-pupillary light reflex (P)-spontaneous respiratory (R) scale. From July 1, 2023 to January 31, 2024, the comatose neurocritical patients, admitted to our hospital and determined as brain death ultimately, were prospectively included as the prospectively group (n=51). In the prospectively group, the the efficacy of constructed GCS-P-R scale was verified. The comparison of quantitative data between groups was conducted with group t-test, and Logistic regression was used to analyze the risk factors for the progression of brain death in comatose neurocritical patients within 14 d after brain injury. The sensitivity and specificity of GCS-P-R scale and GCS were caculated in determining the progression to brain death in comatose neurocritical patients within 14 d after brain injury, and compared with chi square test. P<0.05 was indicated statistical significance of the difference.
Results
In the retrospective group, statistical analysis showed that GCS=3 (OR=3.86, 95%CI: 1.57-18.21), disappearance of light reflex in unilateral pupil (OR=6.83, 95%CI: 4.35-19.34), and the frequency of spontaneous respiratory less than the set frequency (OR=4.16, 95%CI: 1.63-15.52) were the related factors with the progression to brain death within 14 d after brain injury. The GCS-P-R scale score≤0 can be used for early identification of potential organ donors after brain death. In the prospective group, 41 cases (80.4%) progressed to brain death within 14 d after brain injury. According to the GCS-P-R scale score ≤ 0, the sensitivity and specificity of predicting brain death progression within 14 d after brain injury were 92.7% and 43.5%, respectively. The sensitivity and specificity of predicting brain death within 14 d after brain injury based on GCS ≤ 6 were 100% and 0, respectively, the difference of sensitivity between the two groups was statistically significant (χ2=4.898, P<0.05), indicating that the constructed GCS-P-R scale has better predictive performance than GCS.
Conclusions
The GCS-P-R scale which includes pupillary light reflex and spontaneous respiratory assessment, can more accurately predict the progression to brain death within 14 d in comatose neurocritical patients, and can be used for early identification of potential organ donors after brain death.
To investigate the physicochemical factors influencing the activity of snake venom fibrolase (SVF) and to explore the feasibility of enhancing the therapeutic efficacy of SVF in kidneys from donation after cardiac death (DCD) through optimization of thrombolytic conditions.
Methods
A rat model of 60-minutes warm ischemia (WI) DCD kidneys was established. Five groups were included: blank control group, WI group (60 mins), SVF-optimized thrombolysis group, SVF control group, and Alteplase+ plasminogen (PLG) control group, with 3 rats in each group. The extent of thrombus formation in kidney tissues was assessed by hematoxylin-eosin (HE) staining and immunofluorescence. The effects of temperature, pH, and ion concentrations on SVF activity were evaluated in vitro to determine optimal thrombolytic conditions. Kidneys were pre-perfused with the optimized SVF solution, and the therapeutic effects were assessed via histological analysis and measurement of D-dimer levels in venous outflow.
Results
SVF exhibited optimal enzymatic activity at pH 8, 37 ℃, and 4 mmol/L Mg2+. Under in vitro conditions, SVF reached the fibrinolytic plateau significantly faster than Alteplase+ PLG (6 minutes vs. 20 minutes). Immunofluorescence analysis showed that in the SVF-optimized group, no obvious fibrinogen (FBG) fluorescence was detected around the glomeruli in the renal cortex, and FBG fluorescence in the medulla was markedly reduced compared to the SVF control and Alteplase+ PLG groups. HE staining demonstrated near-complete clearance of red blood cells (RBCs) in the cortex and absence of RBCs in the medullary vessels in the SVF-optimized group. The D-dimer level in the SVF-optimized group was significantly higher [(3 069±186) ng/mL] than that in the SVF control group [(1 271±96) ng/mL] and the Alteplase+ PLG control group [(939±152) ng/mL] (all P<0.05).
Conclusion
Optimization of enzymatic reaction conditions significantly enhances the therapeutic efficacy of SVF in thrombolytic treatment of DCD kidneys, showing superior performance compared to Alteplase + PLG.
To investigate the current status of immunosuppressive medication adherence and its influencing factors among kidney transplant recipients, and to provide evidence for improving their medication adherence.
Methods
A convenience sampling method was used to recruit 244 kidney transplant recipients who visited Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University between January 2024 and June 2024. Data were collected through both paper-based and electronic questionnaires, including a general information survey, the basel assessment of adherence to immunosuppressive medication scale (BAASIS), fatigue resistance ambulation illnesses and loss of weight (FRAIL) scale and the ehealth literacy scale (eHEALS). For normally distributed continuous data, intergroup comparisons were performed using independent samples t-test or one-way analysis of variance. Pearson correlation analysis and multiple linear regression were performed to examine the relationship among immunosuppressive medication adherence, frailty, and ehealth literacy, as well as to identify factors influencing immunosuppressive medication adherence. P<0.05 was considered statistically significant.
Results
The valid response rate was 99.2% (242/244). The mean total BAASIS scores were (4.56±1.10), with 161 recipients (66.5%) demonstrating good adherence to immunosuppressive medication, while 81 (33.47%) exhibited suboptimal adherence in at least one aspect. The median FRAIL score was 0 (0-1), and the mean eHEALS scores were (19.64±5.91). Significant differences in immunosuppressive medication adherence of BAASIS scores were observed across age groups, marital status, and time since transplantation (t=3.925, 4.358 and 5.855, all P<0.05). Immunosuppressive medication adherence was positively correlated with frailty (r=0.182, P<0.05). Multiple linear regression analysis identified that the frailty as a risk factor for poor immunosuppressive medication adherence (P<0.05).
Conclusion
Immunosuppressive medication adherence among kidney transplant recipients remains suboptimal, with frailty being a significant risk factor.
To explore the establishment of a cooling off period in the process of living organ donation based on the Delphi method.
Methods
Through literature review and expert discussion, the definition, classification, and grouping suggestions for the cooling off period of living organ donation have been preliminarily determined. A questionnaire was distributed via email, and after three rounds of consultation, consensus was reached on the definition, classification, and grouping methods of the cooling off period, and the duration of the cooling off period was determined.
Results
The cooling off period for living organ donation referred to the shortest time interval between obtaining all necessary information about organ donation and submitting an application for living organ donation for the intended donor. Living organ donation was divided into three categories: (1) liver donation; (2) lung donation; (3) kidney donation/small intestine donation/pancreas donation. Liver donation was divided into high-risk, medium-risk, and low-risk groups based on the model for end-stage liver disease score and pediatric end-stage liver disease score of organ recipients. Lung donation aged ≥ 12 years was divided into high-risk, medium-risk, and low-risk groups based on the lung allocation score of organ recipients, while aged<12 years was divided into high-risk and low-risk groups based on medical urgency. Kidney donation/small intestine donation/pancreas donation were not grouped. The cooling off period for high-risk liver and lung donation groups was 1 d, for medium-risk groups was 7 d, and for low-risk groups was 14 d. The cooling off period for kidney donation/small intestine donation/pancreas donation was 14 d.
Conclusion
Based on three rounds of Delphi method consultation, the definition, classification and grouping method, and duration setting of the cooling off period for living organ donation were determined.
High-sensitized patients possess a large number of HLA antibodies in their bodies, which can lead to rejection of the transplanted kidney and severely affect the success rate of transplant surgeries, necessitating desensitization treatment. Plasmapheresis is an effective desensitization method. Recent studies have shown that plasmapheresis can improve the effectiveness of desensitization treatment during the perioperative period for kidney transplant recipients and enhance the immune response of the body. By formulating targeted plasmapheresis application strategies before and after surgery, it is possible to effectively reduce HLA antibody levels, increase the success rate of desensitization treatment, and facilitate the smooth progress of kidney transplant surgeries.However, plasmapheresis may lead to postoperative complications such as hypocalcemia, infection and hypotension in kidney transplant recipients, which can be mitigated through the implementation of targeted preventive measures.This article reviews the research progress of plasmapheresis for desensitization treatment in kidney transplant recipients during the perioperative period, combining both domestic and international studies, to provide a scientific basis for improving the effectiveness and safety of plasmapheresis in desensitization treatment for kidney transplant recipients.