Genome-wide meta-analysis associates donor-recipient non-HLA genetic mismatch with acute cellular rejection post-liver transplantation.

Background: Acute cellular rejection (ACR) remains a common complication causing significant morbidity post-liver transplantation. Non-human leukocyte antigen (non-HLA) mismatches were associated with an increased risk of ACR in kidney transplantation. Therefore, we hypothesized that donor-recipient non-HLA genetic mismatch is associated with increased ACR incidence post-liver transplantation.

Donor-specific immune senescence as a candidate biomarker of operational tolerance following liver transplantation in adults: Results of a prospective, multicenter cohort study.

Immunosuppression can be withdrawn from selected liver transplant recipients, although robust clinical predictors of tolerance remain elusive. The Immune Tolerance Network ITN056ST study (OPTIMAL; NCT02533180) assessed clinical outcomes and mechanistic correlates of phased immunosuppression withdrawal (ISW) in nonautoimmune, nonviral adult liver transplant recipients. Enrolled subjects were ≥3 years posttransplant with minimal/absent inflammation or fibrosis on a screening liver biopsy.

Donor and recipient genetics: Implications for the development of posttransplant diabetes mellitus.

Posttransplant diabetes mellitus (PTDM) is a prevalent complication of liver transplantation and is associated with cardiometabolic complications. We studied the consequences of genetic effects of liver donors and recipients on PTDM outcomes, focusing on the diverse genetic pathways related to insulin that play a role in the development of PTDM. One thousand one hundred fifteen liver transplant recipients without a pretransplant diagnosis of type 2 diabetes mellitus (T2D) and their paired donors recruited from 2 transplant centers had polygenic risk scores (PRS) for T2D, insulin secretion, and insulin sensitivity calculated.

Disentangling the neural correlates of agency, ownership and multisensory processing.

The experience of the self as an embodied agent in the world is an essential aspect of human consciousness. This experience arises from the feeling of control over one's bodily actions, termed the Sense of Agency, and the feeling that the body belongs to the self, Body Ownership. Despite longstanding philosophical and scientific interest in the relationship between the body and brain, the neural systems involved in Body Ownership and Sense of Agency, and especially their interactions, are not yet understood.

Connectomics of the vertical lobe provides insight into conserved and novel principles of a memory acquisition network.

Here, we present the first analysis of the connectome of a small volume of the vertical lobe (VL) a brain structure mediating the acquisition of long-term memory in this behaviorally advanced mollusk. Serial section electron microscopy revealed new types of interneurons, cellular components of extensive modulatory systems, and multiple synaptic motifs. The sensory input to the VL is conveyed via~1.

Loneliness in Intimate Relationships Scale (LIRS): Development and Validation.

Intimate relationships have been shown to be loneliness positively related to self-esteem. Happiness and well-being and have also been regarded as a buffer against loneliness. Nevertheless, substantive research indicates that intimate relationships and marriage can produce or result in loneliness and thus seriously affect the person's physical, emotional and spiritual well-being.

The Course of LIRADS 3 and 4 Hepatic Abnormalities as Correlated With Explant Pathology: A Single Center Experience.

Background And Aims: The Liver Reporting and Data System (LI-RADS) is the standard classification of imaging findings of hepatic abnormalities for hepatocellular carcinoma (HCC) surveillance. We aimed to study the course of LI-RADS 3 and 4 (LR-3 and LR-4) abnormalities through correlations with explant pathology.

Methods: A single center retrospective study of liver transplant recipients between January 2016 and September 2019 with HCC on explant pathology was conducted.

RadArnomaly: Protecting Radar Systems from Data Manipulation Attacks.

Radar systems are mainly used for tracking aircraft, missiles, satellites, and watercraft. In many cases, information regarding the objects detected by a radar system is sent to, and used by, a peripheral consuming system, such as a missile system or a graphical user interface used by an operator. Those systems process the data stream and make real-time operational decisions based on the data received.

Donor and recipient polygenic risk scores influence the risk of post-transplant diabetes.

Post-transplant diabetes mellitus (PTDM) reduces allograft and recipient life span. Polygenic risk scores (PRSs) show robust association with greater risk of developing type 2 diabetes (T2D). We examined the association of PTDM with T2D PRS in liver recipients (n = 1,581) and their donors (n = 1,555), and kidney recipients (n = 2,062) and their donors (n = 533).

Incidence of acute rejection and patient survival in combined heart-liver transplantation.

Combined heart-liver transplantation (CHLT) is indicated for patients with concomitant end-stage heart and liver disease or patients with amyloid heart disease where liver transplantation mitigates progression. Limited data suggest that the liver allograft provides immunoprotection for heart and kidney allografts in combined transplantation from the same donor. We hypothesized that CHLT reduces the incidence of acute cellular rejection (ACR) and the development of de novo donor-specific antibodies (DSAs) compared with heart-alone transplantation (HA).

Impact of Donor and Recipient Clinical Characteristics and Hepatic Histology on Steatosis/Fibrosis Following Liver Transplantation.

Background: Deceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients.

Methods: Using the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected.

Functional Characterization of Organoids Derived From Irreversibly Damaged Liver of Patients With NASH.

Background And Aims: NASH will soon become the leading cause of liver transplantation in the United States and is also associated with increased COVID-19 mortality. Currently, there are no Food and Drug Administration-approved drugs available that slow NASH progression or address NASH liver involvement in COVID-19. Because animal models cannot fully recapitulate human NASH, we hypothesized that stem cells isolated directly from end-stage liver from patients with NASH may address current knowledge gaps in human NASH pathology.

Occult Hepatocellular Carcinoma Associated With Transjugular Intrahepatic Portosystemic Shunts in Liver Transplant Recipients.

Transplant eligibility for hepatocellular carcinoma (HCC) is determined by the imaging identification of tumor burden within the Milan criteria. Transjugular intrahepatic portosystemic shunt(s) (TIPS) reduce portal hypertension but may impact HCC visualization. It was hypothesized that the presence of pretransplant TIPS would correlate with occult HCC and reduced survival.

Successful transatlantic bilateral hand transplant in a young female highly sensitized to HLA class II antigens.

Vascularized composite allografts may be more susceptible to rejection than other types of organ transplants, particularly in sensitized recipients. We describe a successful transatlantic bilateral hand transplant in a 40-year old woman who was highly sensitized to class II HLA antigens including HLA-DPB1 (UNet CPRA = 86%). Prior to transplantation, we selected an upper limb donor based on HLA class II matching and absence of donor specific antibodies, given evidence that class II mismatches are associated with acute cellular rejection in hand transplants.

Predictors, Presentation, and Treatment Outcomes of Recurrent Hepatocellular Carcinoma After Liver Transplantation: A Large Single Center Experience.

Background: Liver transplantation (LT) is an accepted therapeutic option for hepatocellular carcinoma (HCC) in patients with cirrhosis. Despite careful candidate selection, HCC recurrence occurs. We aimed to describe the predictors of recurrence, clinical presentation, and predictors of survival after HCC recurrence post-LT.

Analysis of Outcomes in Living Donor Liver Transplants Involving Reconstructive Microsurgeons.

Background:  Living donor transplantation is becoming increasingly popular as a modality for patients necessitating liver transplantation. Hepatic artery thrombosis (HAT) remains the most feared acute postoperative complication associated with living-donor liver transplantation. Preoperative planning, including scheduling reconstructive microsurgeons to perform the hepatic artery anastomosis using a surgical microscope or loupes, can decrease HAT rates.

Deletion of donor-reactive T cell clones after human liver transplant.

We recently developed a high throughput T cell receptor β chain (TCRβ) sequencing-based approach to identifying and tracking donor-reactive T cells. To address the role of clonal deletion in liver allograft tolerance, we applied this method in samples from a recent randomized study, ITN030ST, in which immunosuppression withdrawal was attempted within 2 years of liver transplantation. We identified donor-reactive T cell clones via TCRβ sequencing following a pre-transplant mixed lymphocyte reaction and tracked these clones in the circulation following transplantation in 3 tolerant and 5 non-tolerant subjects.

Genetic and Epigenetic Fine Mapping of Complex Trait Associated Loci in the Human Liver.

Deciphering the impact of genetic variation on gene regulation is fundamental to understanding common, complex human diseases. Although histone modifications are important markers of gene regulatory elements of the genome, any specific histone modification has not been assayed in more than a few individuals in the human liver. As a result, the effects of genetic variation on histone modification states in the liver are poorly understood.

Pediatric vascularized composite allotransplantation: What is the landscape for obtaining appropriate donors in the United States?

Listing the world's first pediatric bilateral hand transplant patient for a donor posed many challenges including matching the appropriate donor age, bone size, skin tone, and growth potential in an already limited donor population. This study describes the prevalence and distribution of potential pediatric VCA donors in the United States. We assessed the UNOS database from 2008 to 2015 to identify the prevalence of potential pediatric VCA donors.