Proteomics in Acute Heart Transplant Rejection, On Behalf of the GRAfT Investigators.

Background: Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets.

Methods: Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate.

Results: Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR).

Pathologist interrater reliability and clinical implications of elevated donor-derived cell-free DNA beyond heart transplant rejection, on behalf of the GRAfT investigators.

Background: There is significant variability among pathologists in the histopathological interpretation of the endomyocardial biopsy (EMB) for acute cellular rejection (ACR), and assessment of variability in the interpretation of antibody-mediated rejection (AMR) has not been reported. In contemporary practice, the strategy of allograft surveillance with donor-derived cell-free DNA (dd-cfDNA) compared to EMB has not been compared with a focus on long-term clinical outcomes beyond acute rejection (AR).

Methods: The Genomic Research Alliance for Transplantation is a multicenter, prospective cohort study that enrolled patients from 2015 to 2020.

Malignancy following solid organ transplantation: Current techniques for determination of donor versus recipient origin.

Among the post-transplantation complications that patients may encounter, the transmission of a donor-derived malignant neoplasm is uncommon but potentially life threatening. The determination of donor versus recipient origin is essential particularly in the setting of multiple transplant recipients from the donor. Advances in molecular biology now allow accurate discrimination utilizing routine tissue samples in a timely and cost-effective manner.

Hepatitis B transmission/reactivation associated with Hepatitis B core antibody and Hepatitis C nucleic acid testing positive organs: A report from the Organ Procurement and Transplantation Network Disease Transmission Advisory Committee.

Background: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation.

Aim: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy.

Structurally constrained and pathology-aware convolutional transformer generative adversarial network for virtual histology staining of human coronary optical coherence tomography images.

Significance: There is a significant need for the generation of virtual histological information from coronary optical coherence tomography (OCT) images to better guide the treatment of coronary artery disease (CAD). However, existing methods either require a large pixel-wise paired training dataset or have limited capability to map pathological regions.

Aim: The aim of this work is to generate virtual histological information from coronary OCT images, without a pixel-wise paired training dataset while capable of providing pathological patterns.

Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators.

Background: Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. We hypothesized that this risk may be associated with higher levels of donor-derived cell-free DNA (dd-cfDNA) and cell-free mitochondrial DNA.

Methods: The Genomic Research Alliance for Transplantation is a multicenter, prospective, longitudinal cohort study.

Organizing pneumonia is associated with molecular allograft injury and the development of antibody-mediated rejection.

Background: The association between organizing pneumonia (OP) after lung transplantation with the development of acute rejection (AR) remains undefined. In addition, molecular allograft injury, as measured by donor-derived cell-free DNA (dd-cfDNA), during episodes of OP and its relationship to episodes of AR, chronic lung allograft dysfunction (CLAD), or death is unknown.

Methods: This multicenter, prospective cohort study collected serial plasma samples from 188 lung transplant recipients for dd-cfDNA at the time of bronchoscopy with biopsy.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

Background: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs.

Methods: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement.

Clinical features and allograft failure rates of pulmonary antibody-mediated rejection categories.

Background: Pulmonary antibody-mediated rejection (AMR) consensus criteria categorize AMR by diagnostic certainty. This study aims to define the clinical features and associated outcomes of these recently defined AMR categories.

Methods: Adjudication committees reviewed clinical data of 335 lung transplant recipients to define clinical or subclinical AMR based on the presence of allograft dysfunction, and the primary endpoints, time from transplant to allograft failure, a composite endpoint of chronic lung allograft dysfunction and/or death.

infective endocarditis after lung transplantation: a case report and review of the literature.

infective endocarditis is rarely reported. In this report, we present a case of infective endocarditis secondary to in a lung-transplant recipient and review the relevant literature. A 65-year-old man was hospitalized with hypoxemic respiratory failure and underwent left-sided single lung transplantation.

A clinically relevant model of acute respiratory distress syndrome in human-size swine.

Despite over 30 years of intensive research for targeted therapies, treatment of acute respiratory distress syndrome (ARDS) remains supportive in nature. With mortality upwards of 30%, a high-fidelity pre-clinical model of ARDS, on which to test novel therapeutics, is urgently needed. We used the Yorkshire breed of swine to induce a reproducible model of ARDS in human-sized swine to allow the study of new therapeutics, from both mechanistic and clinical standpoints.

Circulating microRNAs in cellular and antibody-mediated heart transplant rejection.

Background: Noninvasive monitoring of heart allograft health is important to improve clinical outcomes. MicroRNAs (miRs) are promising biomarkers of cardiovascular disease and limited studies suggest they can be used to noninvasively diagnose acute heart transplant rejection.

Methods: The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter prospective cohort study that phenotyped heart transplant patients from 5 mid-Atlantic centers.

Pathological remodeling of distal lung matrix in end-stage cystic fibrosis patients.

Background: Manifestations of cystic fibrosis, although well-characterized in the proximal airways, are understudied in the distal lung. Characterization of the cystic fibrosis lung 'matrisome' (matrix proteome) has not been previously described, and could help identify biomarkers and inform therapeutic strategies.

Methods: We performed liquid chromatography-mass spectrometry, gene ontology analysis, and multi-modal imaging, including histology, immunofluorescence, and electron microscopy for a comprehensive evaluation of distal human lung extracellular matrix (matrix) structure and composition in end-stage cystic fibrosis.

Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy.

Background: Familial hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and is typically caused by mutations in genes encoding sarcomeric proteins that regulate cardiac contractility. HCM manifestations include left ventricular hypertrophy and heart failure, arrythmias, and sudden cardiac death. How dysregulated sarcomeric force production is sensed and leads to pathological remodeling remains poorly understood in HCM, thereby inhibiting the efficient development of new therapeutics.

Comparison of donor-derived cell-free DNA between single versus double lung transplant recipients.

Plasma donor-derived cell-free DNA (dd-cfDNA) is a sensitive biomarker for the diagnosis of acute rejection in lung transplant recipients; however, differences in dd-cfDNA levels between single and double lung transplant remains unknown. We performed an observational analysis that included 221 patients from two prospective cohort studies who had serial measurements of plasma dd-cfDNA at the time of bronchoscopy and pulmonary function testing, and compared dd-cfDNA between single and double lung transplant recipients across a range of disease states. Levels of dd-cfDNA were lower for single vs.

Higher levels of allograft injury in black patients early after heart transplantation.

Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant.

Surveillance for disease progression of transthyretin amyloidosis after heart transplantation in the era of novel disease modifying therapies.

Background: Heart Transplantation (HT) is a rational therapy for advanced transthyretin cardiac amyloidosis (ATTR-CA), but the impact of ongoing amyloid deposition is not well defined. We evaluated a cohort of patients who underwent HT for ATTR-CA to determine the incidence of de novo or progression of post-HT ATTR deposition.

Methods: All patients who were followed post-HT for ATTR-CA at our center were included.

Can lightning strike twice? Wild-type transthyretin cardiac amyloidosis associated with rare liver disease.

Wild-type ATTR cardiac amyloidosis (ATTRwt-CA) is not as rare as previously thought to be. Patients with infiltrative cardiac amyloidosis often present with right-sided heart failure (HF) symptomatology. Clinically significant liver disease and cirrhosis has not been reported in ATTRwt-CA.