Process Variation in Liver, Kidney, and Pancreas Transplantation: A Multicenter Evaluation From the Consortium for the Holistic Assessment of Risk in Transplant.

Background: Transplant center processes for determining candidacy are complex, poorly documented, ambiguous, and variable across centers. Opaque and nonstandardized transplant processes can compromise data collection and lead to inconsistent outcomes.

Methods: To understand process variation and data quality in transplantation, we surveyed 8 abdominal transplant centers in an existing research consortium about their processes of care for liver, kidney, and pancreas transplants.

Antibodies to angiotensin II type 1 receptor and endothelin type A receptor are associated with cytokine production enriched for type 2 immune response and antibody production in pediatric kidney transplant recipients.

Activating antibodies to angiotensin II type 1 receptor (AT1R) and endothelin type A receptor (ETAR) have been associated with rejection, allograft loss, decline in allograft function, and development of human leukocyte antigen donor-specific antibodies in kidney transplantation. Understanding immune dysregulation and inflammatory signatures associated with these antibodies is important for generating targeted investigations of pathogenesis. We investigated a panel of 38 cytokines in a multicenter cohort of 133 pediatric kidney transplant recipients with 1 to 2 years of follow up to further elucidate AT1R and ETAR-Ab-associated inflammatory signatures.

The Use of Artificial Intelligence in Residency Application Evaluation-A Scoping Review.

Several residency programs have begun investigating artificial intelligence (AI) methods to facilitate application screening processes. However, no unifying guidelines for these methods exist. We sought to perform a scoping review of AI model development and use in residency/fellowship application review, including if bias was explored.

Donor-specific mesenchymal stem cell infusion in human and nonhuman primate kidney transplantation.

We report the results of 2 independent, concurrently performed studies evaluating the safety and efficacy of donor-derived mesenchymal stromal cell (MSC) infusions in inducing immune-tolerance in nonhuman primate (NHP) and human kidney transplant recipients treated with depletional induction and belatacept/sirolimus maintenance. Fifteen NHPs received rhesus ATG induction and were divided into 3 groups: control (n = 6), pretransplant thymic irradiation (n = 4), and thymic irradiation with monthly donor-MSC infusion (n = 5). Sirolimus was discontinued at day-180, and belatacept at day-365 posttransplant.

Development of Multiservice Machine Learning Models to Predict Postsurgical Length of Stay and Discharge Disposition at the Time of Case Posting.

Objective: Develop machine learning (ML) models to predict postsurgical length of stay (LOS) and discharge disposition (DD) for multiple services with only the data available at the time of case posting.

Background: Surgeries are scheduled largely based on operating room resource availability with little attention to downstream resource availability such as inpatient bed availability and the care needs after hospitalization. Predicting postsurgical LOS and DD at the time of case posting could support resource allocation and earlier discharge planning.

Ambulatory Surgery Ensemble: Predicting Adult and Pediatric Same-Day Surgery Cases Across Specialties.

Objective: To develop an ensemble model using case-posting data to predict which patients could be discharged on the day of surgery.

Background: Few models have predicted which surgeries are appropriate for day cases. Increasing the ratio of ambulatory surgeries can decrease costs and inpatient bed utilization while improving resource utilization.

Development of a natural language processing algorithm to extract social determinants of health from clinician notes.

Disparities in access to the organ transplant waitlist are well-documented, but research into modifiable factors has been limited due to a lack of access to organized prewaitlisting data. This study aimed to develop a natural language processing (NLP) algorithm to extract social determinants of health (SDOH) from free-text notes and quantify the association of SDOH with access to the transplant waitlist. We collected 261 802 clinician notes from 11 111 adults referred for kidney or liver transplants between 2016 and 2022 at the Duke University Health System.

Acute perioperative alterations in metabolism: A pilot study using mass spectrometry-based metabolomics.

Objective: To characterize early physiologic stresses imposed by surgery by applying metabolomic analyses to deeply phenotype pre- and postoperative plasma and urine of patients undergoing elective surgical procedures.

Background: Patients experience perioperative stress through depletion of metabolic fuels. Bowel stasis or injury might allow more microbiome-derived uremic toxins to enter the blood, while the liver and kidney are simultaneously clearing analgesic and anesthetic drugs.

Immunomodulation of T cell-mediated alloimmunity by proximity to endothelial cells under the mammalian target of rapamycin blockade.

Endothelial cells (ECs) are an initial barrier between vascularized organ allografts and the host immune system and are thus well positioned to initiate and influence alloimmune rejection. The mammalian target of rapamycin inhibitor rapamycin is known to inhibit T cell activation and attenuate acute allograft rejection. It also has numerous effects on ECs.

Rapamycin Prevents Expansion of Costimulation Blockade-resistant CD8+ Alloreactive Memory Cells following Depletional Induction in Renal Transplant Recipients.

Alemtuzumab induction with belatacept/rapamycin-based maintenance immunotherapy (ABR) prevents kidney allograft rejection and specifically limits early costimulation blockade-resistant rejection (CoBRR). To evaluate the mechanisms by which this regimen alters CoBRR, we characterized the phenotype and functional response of preexisting memory cells to allogeneic endothelial cells using intracellular cytokine staining and flow cytometry. IL-7-induced lymphocyte proliferation in the presence or absence of rapamycin was assessed to characterize the phenotype of proliferating cells.

Advancing mouse models for transplantation research.

Mouse models have been instrumental in understanding mechanisms of transplant rejection and tolerance, but cross-study reproducibility and translation of experimental findings into effective clinical therapies are issues of concern. The Mouse Models in Transplantation symposium gathered scientists and physician-scientists involved in basic and clinical research in transplantation to discuss the strengths and limitations of mouse transplant models and strategies to enhance their utility. Participants recognized that increased procedure standardization, including the use of prespecified, defined endpoints, and statistical power analyses, would benefit the field.

Defining the Need for Causal Inference to Understand the Impact of Social Determinants of Health: A Primer on Behalf of the Consortium for the Holistic Assessment of Risk in Transplantation (CHART).

Objective: This study aims to introduce key concepts and methods that inform the design of studies that seek to quantify the causal effect of social determinants of health (SDOH) on access to and outcomes following organ transplant.

Background: The causal pathways between SDOH and transplant outcomes are poorly understood. This is partially due to the unstandardized and incomplete capture of the complex interactions between patients, their neighborhood environments, the tertiary care system, and structural factors that impact access and outcomes.

The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates.

Prior studies of anti-CD40 ligand (CD40L)-based immunosuppression demonstrated effective prevention of islet and kidney allograft rejection in nonhuman primate models; however, clinical development was halted because of thromboembolic complications. An anti-CD40L-specific monoclonal antibody, AT-1501 (Tegoprubart), was engineered to minimize risk of thromboembolic complications by reducing binding to Fcγ receptors expressed on platelets while preserving binding to CD40L. AT-1501 was tested in both a cynomolgus macaque model of intrahepatic islet allotransplantation and a rhesus macaque model of kidney allotransplantation.

Development, Deployment, and Implementation of a Machine Learning Surgical Case Length Prediction Model and Prospective Evaluation.

Objective: To implement a machine learning model using only the restricted data available at case creation time to predict surgical case length for multiple services at different locations.

Background: The operating room is one of the most expensive resources in a health system, estimated to cost $22 to $133 per minute and generate about 40% of hospital revenue. Accurate prediction of surgical case length is necessary for efficient scheduling and cost-effective utilization of the operating room and other resources.

American Society of Transplant Surgeons-American Society of Transplantation report of FDA meeting on regulatory expectations for xenotransplantation products.

In June 2022, the US Food and Drug Administration Center for Biologics Evaluation and Research held the 73rd meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee for public discussion of regulatory expectations for xenotransplantation products. The members of a joint American Society of Transplant Surgeons/American Society of Transplantation committee on xenotransplantation compiled a meeting summary focusing on 7 topics believed to be key by the committee: (1) preclinical evidence supporting progression to a clinical trial, (2) porcine kidney function, (3) ethical aspects, (4) design of initial clinical trials, (5) infectious disease issues, (6) industry perspectives, and (7) regulatory oversight.

Xenorecognition and costimulation of porcine endothelium-derived extracellular vesicles in initiating human porcine-specific T cell immune responses.

Porcine vascular endothelial cells (PECs) form a mechanistic centerpiece of xenograft rejection. Here, we determined that resting PECs release swine leukocyte antigen class I (SLA-I) but not swine leukocyte antigen class-II DR (SLA-DR) expressing extracellular vesicles (EVs) and investigated whether these EVs proficiently initiate xenoreactive T cell responses via direct xenorecognition and costimulation. Human T cells acquired SLA-I EVs with or without direct contact to PECs, and these EVs colocalized with T cell receptors.

Immune Phenotype and Postoperative Complications After Elective Surgery.

Objectives: To characterize and quantify accumulating immunologic alterations, pre and postoperatively in patients undergoing elective surgical procedures.

Background: Elective surgery is an anticipatable, controlled human injury. Although the human response to injury is generally stereotyped, individual variability exists.

A random forest model using flow cytometry data identifies pulmonary infection after thoracic injury.

Background: Thoracic injury can cause impairment of lung function leading to respiratory complications such as pneumonia (PNA). There is increasing evidence that central memory T cells of the adaptive immune system play a key role in pulmonary immunity. We sought to explore whether assessment of cell phenotypes using flow cytometry (FCM) could be used to identify pulmonary infection after thoracic trauma.

A comparison of deprivation indices and application to transplant populations.

The choice of deprivation index can influence conclusions drawn regarding the extent of deprivation within a community and the identification of the most deprived communities in the United States. This study aimed to determine the degree of correlation among deprivation indices commonly used to characterize transplant populations. We used a retrospective cohort consisting of adults listed for liver or kidney transplants between 2008 and 2018 to compare 4 deprivation indices: neighborhood deprivation index, social deprivation index (SDI), area deprivation index, and social vulnerability index.