Analysis of the primary factors influencing donor derived cell-free DNA testing in kidney transplantation.

The donor-derived cell-free DNA (ddcfDNA) is found in the plasma and urine of kidney transplant recipients and displays notable potential in diagnosing rejection, specifically antibody-mediated rejection (ABMR). Nonetheless, the quantitative methods of ddcfDNA lacking standardization and diverse detection techniques can impact the test outcomes. Besides, both the fraction and absolute values of ddcfDNA have been reported as valuable markers for rejection diagnosis, but they carry distinct meanings and are special in various pathological conditions. Additionally, ddcfDNA is highly sensitive to kidney transplant injury. The various sampling times and combination with other diseases can indeed impact ddcfDNA detection values. This review comprehensively analyses the various factors affecting ddcfDNA detection in kidney transplantation, including the number of SNPs and sequencing depths. Furthermore, different pathological conditions, distinct sampling time points, and the presence of complex heterologous signals can influence ddcfDNA testing results in kidney transplantation. The review also provides insights into ddcfDNA testing on different platforms along with key considerations.

Mechanical Preservation and Delayed Graft Function and Hospital Length of Stay as Deployed in the United States: Analysis of the Last Decade.

BACKGROUND Mechanical preservation (MP) of deceased donor kidney transplants showed a 30% to 50% reduction in delayed graft function (DGF) as defined by dialysis in the first week, when compared with cold storage. DGF is associated with longer hospital stays and increased costs. In this study, we sought to understand the impact of MP on rates of DGF and length of hospital stays in a contemporary cohort of deceased donor kidney transplants in the United States. MATERIAL AND METHODS All single deceased donor kidney transplants performed between January 1, 2010, and September 2, 2020, were identified in the Scientific Registry of Transplant Recipients database. Donor kidneys were considered pumped if the transplant center received the kidney on the pump. RESULTS Multivariate logistic regression showed that MP had similar odds of reduction of DGF for all subsets of donors. The unadjusted rate of DGF for pumped brain-dead standard criteria donor (BDSCD) recipients was similar to that of donors stored on ice. The rate of DGF for expanded criteria donors (ECD) and donors after cardiac death (DCD) was lower in the recipients who received MP. The similar DGF rates in BDSCD donor recipients were due to longer cold ischemia times in MP kidneys. The lower DGF rates seen in ECD and DCD recipients of pumped kidneys did not translate into a shortened length of hospitalization after transplant. CONCLUSIONS As currently deployed, only DCD and ECD donor recipients of MP kidneys experienced a lower DGF rate. In all subsets of patients, MP did not appreciably shorten the hospital length of stay.

Bladder and Kidney Transplantation En Bloc: Review of Experience and Prospects for Development.

Although urine bladder transplantation is currently being conducted, the procedure is an incompletely resolved problem in clinical transplantology. A small number of en bloc bladder and kidney transplants from pediatric donors to adult recipients in humans have been reported. A small number of bladder transplants with and without combinations with kidneys have also been performed in experiments on different animal models. Here, we aimed to highlight the experiences of various scientists in bladder transplantation in humans and animals. We also presented our small experience in conducting transplant of 1 kidney, ureters, and a segment of the bladder in an experiment on pigs in 2023 (5 cases), which is a promising direction for further successful development of this technology in humans. In 2024, we plan to conduct another 10 transplants of a single block ofthe kidney and bladderin pigs, results of which will be published after the completion of the experimental work.

Does Antiretroviral Therapy Prevent Human T-Lymphotropic Virus 1 Transmission From a Seropositive Donor to a Kidney Transplant Recipient? A Case Report and Literature Review.

Human T-lymphotropic virus 1 produces a latent infection and disease with poor prognosis. Although its transmission during solid-organ transplant and development of the disease has been described, it is not clear whether antiretroviral treatment could prevent it. We report the first kidney transplant of a donor with human T-lymphotropic virus positivity to a negative recipient who was under antiretroviral treatment without evidence of transmission. We reviewed the literature, which included reports of 55 solid-organ transplant donors with human T-lymphotropic virus positivity to negative recipients, showing high rates of transmission and disease. The benefits of antiretroviral treatment require evaluation in further studies.

Effects of donors' and recipients' preoperative serum sodium on the prognosis of liver transplantation.

Dysnatremia is common in donors and recipients of liver transplantation (LT). However, the influence of dysnatremia on LT prognosis remains controversial. This study aimed to investigate effects of donors' and recipients' serum sodium on LT prognosis. We retrospectively reviewed 248 recipients who underwent orthotopic LT at our center between January 2016 and December 2018. Donors and recipients perioperative and 3-year postoperative clinical data were included. Delta serum sodium was defined as the donors' serum sodium minus the paired recipients' serum sodium. Donors with serum sodium > 145 mmol/L had significantly higher preoperative blood urea nitrogen (BUN) (P < 0.01) and creatinine (Cr) (P < 0.01) than others. Preoperative total bilirubin (TBIL) (P < 0.01), direct bilirubin (DBIL) (P < 0.01), BUN (P < 0.01), Cr (P < 0.01) were significantly higher in the hyponatremia group of recipients than the other groups, but both of donors' and recipients' serum sodium had no effect on the LT prognosis. In the delta serum sodium < 0 mmol/L group, TBIL (P < 0.01) and DBIL (P < 0.01) were significantly higher in postoperative 1 week than the other groups, but delta serum sodium had no effect on the postoperative survival rates. Dysnatremia in donors and recipients of LT have no effect on postoperative survival rates, hepatic and renal function, but recipients with higher serum sodium than donors have significantly higher TBIL and DBIL at 1 week postoperatively.

Identification of the novel HLA-DPB1*21:01:02 allele using nanopore sequencing technology.

HLA-DPB1*21:01:02 differs from HLA-DPB1*21:01:01 by one single nucleotide substitution at position 435 C>T in exon 3.

[The present and future of haploidentical hematopoietic stem cell transplantation in China].

The lack of donors is the biggest obstacle to the widespread use of hematopoietic stem cell transplantation. The establishment and improvement of new transplantation schemes have made haploid hematopoietic stem cell transplantation a clinical routine, benefiting a large number of patients with hematological diseases. Haploid donors have become the most important source of donors for allogeneic hematopoietic stem cell transplantation in China. This article focuses on the current situation and future development trends of haploid hematopoietic stem cell transplantation in China, in order to increase the understanding of clinical doctors on haploid hematopoietic stem cell transplantation.

Normothermic Regional Perfusion in Controlled Donation After Circulatory Death Liver Transplantation: A Systematic Review and Meta-Analysis.

Liver grafts from controlled donation after circulatory death (cDCD) donors have lower utilization rates due to inferior graft and patient survival rates, largely attributable to the increased incidence of ischemic cholangiopathy, when compared with grafts from brain dead donors (DBD). Normothermic regional perfusion (NRP) may improve the quality of cDCD livers to allow for expansion of the donor pool, helping to alleviate the shortage of transplantable grafts. A systematic review and metanalysis was conducted comparing NRP cDCD livers with both non-NRP cDCD livers and DBD livers. In comparison to non-NRP cDCD outcomes, NRP cDCD grafts had lower rates of ischemic cholangiopathy [RR = 0.23, 95% CI (0.11, 0.49), p = 0.0002], primary non-function [RR = 0.51, 95% CI (0.27, 0.97), p = 0.04], and recipient death [HR = 0.5, 95% CI (0.36, 0.69), p < 0.0001]. There was no difference in outcomes between NRP cDCD donation compared to DBD liver donation. In conclusion, NRP improved the quality of cDCD livers compared to their non-NRP counterparts. NRP cDCD livers had similar outcomes to DBD grafts. This provides further evidence supporting the continued use of NRP in cDCD liver transplantation and offers weight to proposals for its more widespread adoption.

Immunopathology of Corneal Allograft Rejection and Donor-Specific Antibodies (DSAs) as Immunological Predictors of Corneal Transplant Failure.

Despite tremendous developments in the field of laboratory testing in transplantation, the rules of eligibility for corneal transplantation still do not include typing of human leukocyte antigens (HLAs) in the donor and recipient or detection of donor-specific antibodies (DSAs) in the patient. The standard use of diagnostic algorithms is due to the cornea belonging to immunologically privileged tissues, which usually determines the success of transplantation of this tissue. A medical problem is posed by patients at high risk of transplant rejection, in whom the immune privilege of the eye is abolished and the risk of transplant failure increases. Critical to the success of transplantation in patients at high risk of corneal rejection may be the selection of an HLA-matched donor and recipient, and the detection of existing and/or de novo emerging DSAs in the patient. Incorporating the assessment of these parameters into routine diagnostics may contribute to establishing immune risk stratification for transplant rejection and effective personalized therapy for patients.

Identification of HIV infection in two solid organ recipients three years after transplantation / Identificación de infección por el virus de la inmunodeficiencia humana en dos receptores de órgano sólido tres años después del trasplante

Routine screening of organ donors to detect human immunodeficiency virus (HIV) infection has detected the rare transmission of the virus through organ transplantation. However, despite routine screening, HIV transmission remains a risk in organ transplantation since, unlike tissues, solid organs cannot be processed, disinfected, or modified to inactivate infectious pathogens. A case of possible transmission of HIV by organ transplant is described below, from a previously seronegative donor to two recipients.

El examen de rutina de los donantes de órganos para detectar la infección por el virus de la inmunodeficiencia humana (HIV) ha hecho que la transmisión del virus mediante el trasplante de órganos sea poco común. Sin embargo, a pesar de las pruebas de detección de rutina, la transmisión del HIV continúa siendo un riesgo del trasplante de órganos ya que, a diferencia de los tejidos, los órganos sólidos no se pueden procesar, desinfectar, ni modificar para inactivar patógenos infecciosos. A continuación, se describe un caso de posible transmisión de HIV por trasplante de órganos de un donante previamente seronegativo a dos de sus receptores.

ATG-Thymoglobulin Versus ATG-Fresenius for Conditioning in Thalassemia Patients Who Underwent Allogenic Stem Cell Transplantation from Matched-Sibling Donor: A Tertiary Cancer Care Center Short-Term Experience.

Graft rejection and Graft-versus-host disease (GVHD) are some of the significant factors resulting in morbidity and mortality following allogeneic hematopoietic cell transplantation. Prophylaxis for GVHD using T-cell depleting agents is helpful in reducing the transplant-related mortality and graft rejection. Both tATG and fATG exhibit varied amounts of antibody specificities and perform distinct immunomodulatory effects, regardless of their capacity to deplete T-lymphocytes. We conducted this single-center, retrospective study at our center to compare both formulations. Twenty-six patients were included in the study, 13 in each cohort. The median age at diagnosis of ß-thalassemia was 5 months (range, 3-12 months) in the tATG group and 6 months (range, 3-9 months) in the f-ATG group, respectively. Acute GVHD was observed in 1 (7.7) and 2(15.4) in the tATG and fATG group, respectively. No cases of chronic GVHD were observed in either group. There was no difference in the mixed chimerism observed at 6 months in both groups, tATG (n = 5, 38.5%) and fATG (n = 6, 46.15). There was 1 (7.6) rejection at day +72 observed in the tATG group, whereas no rejection was observed in the fATG group. At a mean follow-up duration of 288 days since transplant, there were no deaths in either of the groups. In conclusion, both ATG preparations showed equivalent effectiveness in preventing rejections and GVHD. However, further larger studies are required to establish the long-term efficacy and safety of both formulations in ASCT.

Longitudinal analysis of social and community factors effective in increasing the number of liver donors in the United States.

In this research, it was aimed to evaluate of social and community factors effective in increasing the number of liver donors. Descriptive and relational scanning models were used to conduct the research. Data on liver donors was gathered from the USA Health Resources & Services Administration's Organ Procurement and Transplantation Network between 1988 and 2023. The United States (USA) World Bank Country Reports provided the mortality rates. The data was analyzed using Spearman rho correlation, year-controlled partial correlation, and Generalized Linear Model-Logit analysis. Deceased donor numbers were significantly and negatively correlated with government health expenditure (r = -0.816; P < .01), current health expenditure (r = -0.768; P < .01), female education attainment (r = -0.804; P < .01) and Gini index (r = 0.434; P < .05). Living donor numbers were significantly and negatively correlated with government health expenditure (r = -0.731; P < .01), current health expenditure (r = -0.781; P < .01), male percentage (r = -0.786; P < .01), female education attainment (r = -0.640; P < .05), employment (r = 0.751; P < .01), GDP (r = -0.792; P < .01) and Gini index (r = -0.486; P < .01). Living donor numbers were significantly and positively correlated with age dependency (r = 0.815; P < .01). Generalized Linear Model-Logit (GLM-L) results showed that effect of female education attainment had significant contribution on deceased liver donor (B = -3290.605; P < .01). Effects of significantly correlated community factors on living liver donor numbers were found to be statistically insignificant (P > .05). Research findings reveal that among community factors, especially women's participation in education has a statistically significant effect on liver donors. These results show that the health expenditures made over the years do not provide any added value for liver donors, and role of women on liver donor is significantly dominant.

Surgical techniques for cardiac procurement, preparation and perfusion using the Organ Care System.

We provide an audio-visual step-by-step guide to the preparation of a donor heart for the application of normothermic, ex situ cardiac perfusion on the TransMedics Organ Care System using a heart donated after brain death. The use of the Organ Care System increases heart transplantation activity by enabling the utilization of hearts donated after circulatory death, the use of extended criteria grafts and the extension of out-of-body time, which can help overcome geographic or surgical barriers. Ex situ cardiac perfusion is a new technique and is therefore not yet routinely performed in many centres. However, it can be assumed that this technique will become more established and widespread in the future. Our video tutorial, which summarizes all important steps, can therefore be of benefit to surgical teams for planning, training or as a refresher.

An integrated machine learning model enhances delayed graft function prediction in pediatric renal transplantation from deceased donors.

BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.

Informed consent and coercion in recruitment advertisements for oocyte donors.

BACKGROUND: As the use of donor eggs for in vitro treatment has increased, both medically affiliated and private donor egg agencies have turned to online advertisements to recruit donors. The American Society for Reproductive Medicine provides recommendations encouraging ethical recruitment of donors, however there is no formal regulation for the informed consent process for egg donor recruitment and compensation. Underrepresentation of risks and targeted financial incentives may pose a risk to the informed consent process. METHODS: Data from online advertisements for egg donors active between January 1 - August 31, 2020, were collected to analyze content related to risks, Covid-19 precautions, donor payment, and desired donor characteristics. Advertisements for egg donors on Google, Craigslist, and social media were analyzed. Primary outcomes included the mention of the risks of egg donation, including the risk of Covid-19 exposure, in donor egg advertisements. Secondary outcomes included language targeting specific donor characteristics and financial compensation. RESULTS: 103 advertisements were included. 35.9% (37/103) of advertisements mentioned some risk of the egg donation process, and 18.5% (19/103) mentioned risks or precautions related to Covid-19 exposure. Of advertisements for private donor egg agencies, 40.7% (24/59) mentioned any risk, compared to 29.6% (13/44) of medically affiliated egg donation programs; the difference was not statistically significant (p-value = 0.24). Agencies targeting students and donors of a specific race were more likely to offer payments over $10,000 for an egg donation cycle. Among advertisements offering over $20,000 for donor compensation, 72.7% (8/11) recruited women under the age of 21. CONCLUSION: Egg donor recruitment advertisements, for both medically affiliated programs and private agencies, were unlikely to mention risks including the risk of exposure to Covid-19. Non-medically affiliated private donor egg agencies were more likely to violate multiple American Society for Reproductive Medicine ethics guidelines, including offering higher than average compensation, and recruiting donors from young and vulnerable populations.