Maintenance of graft tissue-resident Foxp3+ cells is necessary for lung transplant tolerance in mice.

Mechanisms that mediate allograft tolerance differ between organs. We have previously shown that Foxp3+ T cell-enriched bronchus-associated lymphoid tissue (BALT) is induced in tolerant murine lung allografts and that these Foxp3+ cells suppress alloimmune responses locally and systemically. Here, we demonstrated that Foxp3+ cells that reside in tolerant lung allografts differed phenotypically and transcriptionally from those in the periphery and were clonally expanded.

The Specialized Donor Care Facility Model Improves Operating Room Efficiency.

Background: Organ procurement organizations coordinate organ donation through 2 distinct models of care: the conventional model, in which donors are managed at hospitals where brain death occurs, and the specialized donor care facility (SDCF) model, where brain dead donors are transferred to a freestanding facility. The aim of this study is to compare operating room efficiency for procurements between the SDCF and conventional models of care.

Methods: We performed a prospective analysis of operating room efficiency between thoracic donor procurement operations performed at a SDCF and other organ procurement organizations using the conventional model of care.

"Horses for courses" computed tomography or predicted total lung capacity for size matching in lung transplantation.

Size-matching donors to recipients in lung transplantation continues to be a clinical challenge. Predicted total lung capacity equations, or more simply, donor and recipient heights, while widely used, are imprecise and may not be representative of the pool of donors and recipients. These inherent limitations may result in size discrepancies.

Updated Views on Neutrophil Responses in Ischemia-Reperfusion Injury.

Ischemia-reperfusion injury is an inevitable event during organ transplantation and represents a primary risk factor for the development of early graft dysfunction in lung, heart, liver, and kidney transplant recipients. Recent studies have implicated recipient neutrophils as key mediators of this process and also have found that early innate immune responses after transplantation can ultimately augment adaptive alloimmunity and affect late graft outcomes. Here, we discuss signaling pathways involved in neutrophil recruitment and activation after ischemia-mediated graft injury in solid organ transplantation with an emphasis on lung allografts, which have been the focus of recent studies.

Necroptosis triggers spatially restricted neutrophil-mediated vascular damage during lung ischemia reperfusion injury.

Ischemia reperfusion injury represents a common pathological condition that is triggered by the release of endogenous ligands. While neutrophils are known to play a critical role in its pathogenesis, the tissue-specific spatiotemporal regulation of ischemia-reperfusion injury is not understood. Here, using oxidative lipidomics and intravital imaging of transplanted mouse lungs that are subjected to severe ischemia reperfusion injury, we discovered that necroptosis, a nonapoptotic form of cell death, triggers the recruitment of neutrophils.

Advanced considerations in organ donors.

The rising need for lung transplantation over recent years has not paralleled the availability of suitable lung allografts. The number of lung transplantations performed each year in the United States remains limited by an inadequate supply of suitable donors as well as low donor utilization rates. While several methods have been proposed for increasing the donor pool, there is considerable disparity between acceptance and utilization of these practices among transplant centers.

Innate immunity in lung transplantation.

Innate immune pathways early after pulmonary transplantation have been shown to cause primary graft dysfunction (PGD) and also predispose to late graft failure. Recent studies in animal models have elucidated critical mechanisms governing such innate immune responses. Here, we discuss pathways of inflammatory cell death, triggers for sterile and infectious inflammation, and signaling cascades that mediate lung injury early after transplantation.

Incidentally found rib hemangioma: case report and discussion of management.

Rib hemangioma is a rare chest wall tumor for which few reports in the literature exist to help guide treatment. The clinical presentation, radiographic findings, and treatment strategies vary in the literature, with the majority of patients undergoing surgical resection to definitively rule out malignancy. Here, we report a 23-year-old woman with an incidentally discovered rib hemangioma, who had a history of migraines, during the workup of a severe headache refractory to medical treatment.

Tolerance, immunosuppression, and immune modulation: impacts on lung allograft survival.

Purpose Of Review: Immune responses following lung transplantation continue to result in high rates of allograft failure and rejection, and current immunosuppression does not address the unique immunologic properties of the lung. Here, we review recent studies on lung allograft tolerance and alloimmunity and discuss implications for immunosuppression.

Recent Findings: Processes governing tolerance and alloimmunity in lung allografts differ from other solid organs.

Clinical Outcomes of Lung Transplants From Donors With Unexpected Pulmonary Embolism.

Background: Pulmonary embolism (PE) is unexpectedly detected in some donor lungs during organ procurement for lung transplantation. Anecdotally, such lungs are usually implanted; however, the impact of this finding on recipient outcomes remains unclear. We hypothesized that incidentally detected donor PE is associated with adverse short-term and long-term outcomes among lung transplant recipients.

Donor management using a specialized donor care facility is associated with higher organ utilization from drug overdose donors.

Drug overdoses have tripled in the United States over the last two decades. With the increasing demand for donor organs, one potential consequence of the opioid epidemic may be an increase in suitable donor organs. Unfortunately, organs from donors dying of drug overdose have poorer utilization rates than other groups of brain-dead donors, largely due to physician and recipient concerns about viral disease transmission.

Economic evaluation of the specialized donor care facility for thoracic organ donor management.

Background: Over the last decade two alternative models of donor care have emerged in the United States: the conventional model, whereby donors are managed at the hospital where brain death occurs, and the specialized donor care facility (SDCF), in which brain dead donors are transferred to a SDCF for medical optimization and organ procurement. Despite increasing use of the SDCF model, its cost-effectiveness in comparison to the conventional model remains unknown.

Methods: We performed an economic evaluation of the SDCF and conventional model of donor care from the perspective of U.

Lymphatic drainage from bronchus-associated lymphoid tissue in tolerant lung allografts promotes peripheral tolerance.

Tertiary lymphoid organs are aggregates of immune and stromal cells including high endothelial venules and lymphatic vessels that resemble secondary lymphoid organs and can be induced at nonlymphoid sites during inflammation. The function of lymphatic vessels within tertiary lymphoid organs remains poorly understood. During lung transplant tolerance, Foxp3+ cells accumulate in tertiary lymphoid organs that are induced within the pulmonary grafts and are critical for the local downregulation of alloimmune responses.

Pericardial Mitochondrial DNA Levels Are Associated With Atrial Fibrillation After Cardiac Surgery.

Background: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, and is associated with increased morbidity and mortality. Inflammation has been implicated as an etiology of POAF. Mitochondrial DNA (mtDNA) has been shown to initiate inflammation.

Bacterial products in donor airways prevent the induction of lung transplant tolerance.

Although postoperative bacterial infections can trigger rejection of pulmonary allografts, the impact of bacterial colonization of donor grafts on alloimmune responses to transplanted lungs remains unknown. Here, we tested the hypothesis that bacterial products present within donor grafts at the time of implantation promote lung allograft rejection. Administration of the toll-like receptor 2 (TLR2) agonist Pam Cys to Balb/c wild-type grafts triggered acute cellular rejection after transplantation into B6 wild-type recipients that received perioperative costimulatory blockade.

Shipping Lungs Greater Distances Increases Costs Without Cutting Waitlist Mortality.

Background: On November 24, 2017, a change in lung allocation policy was initiated to replace the donor service area with a 250-nautical-mile radius circle around the donor hospital. We aim to analyze the consequences of this change, including organ acquisition cost and transplant outcomes, at the national level.

Methods: Data on adult patients undergoing lung transplantation between April 27, 2017, and June 22, 2018 (30 weeks before to 30 weeks after allocation policy change) were extracted from the Scientific Registry of Transplant Recipients database.

IL-22 is required for the induction of bronchus-associated lymphoid tissue in tolerant lung allografts.

Long-term survival after lung transplantation remains profoundly limited by graft rejection. Recent work has shown that bronchus-associated lymphoid tissue (BALT), characterized by the development of peripheral nodal addressin (PNAd)-expressing high endothelial venules and enriched in B and Foxp3 T cells, is important for the maintenance of allograft tolerance. Mechanisms underlying BALT induction in tolerant pulmonary allografts, however, remain poorly understood.

The emerging role of regulatory T cells following lung transplantation.

Regulatory T cells (Treg) have proven to be a powerful immunologic force in nearly every organ system and hold therapeutic potential for a wide range of diseases. Insights gained from non-transplant pathologies, such as infection, cancer, and autoimmunity, are now being translated to the field of solid organ transplantation, particularly for livers and kidneys. Recent insights from animal models of lung transplantation have established that Tregs play a vital role in suppressing rejection and facilitating tolerance of lung allografts, and such discoveries are being validated in human studies and preclinical trials.

Ferroptotic cell death and TLR4/Trif signaling initiate neutrophil recruitment after heart transplantation.

Non-apoptotic forms of cell death can trigger sterile inflammation through the release of danger-associated molecular patterns, which are recognized by innate immune receptors. However, despite years of investigation the mechanisms which initiate inflammatory responses after heart transplantation remain elusive. Here, we demonstrate that ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, decreases the level of pro-ferroptotic hydroperoxy-arachidonoyl-phosphatidylethanolamine, reduces cardiomyocyte cell death and blocks neutrophil recruitment following heart transplantation.

Chest computed tomography imaging improves potential lung donor assessment.

Objective: Chest computed tomography (CT) imaging is being increasingly used for potential lung donor assessment. However, the efficacy of CT imaging in this setting remains unknown. We hypothesize that chest CT imaging independently affects the decision-making process in donor lung utilization.

A 20-year multicenter analysis of dialysis-dependent patients who had aortic or mitral valve replacement: Implications for valve selection.

Objective: Valve selection in dialysis-dependent patients can be difficult because long-term survival is diminished and bleeding risks during anticoagulation treatment are greater in patients with renal failure. In this study we analyzed long-term outcomes of dialysis-dependent patients who underwent valve replacement to help guide optimal prosthetic valve type selection.

Methods: Dialysis-dependent patients who underwent aortic and/or mitral valve replacement at 3 institutions over 20 years were examined.