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We are entering 2021 with an expanding and effective COVID-19 vaccine armamentarium. Recent interim results from COVID-19 vaccine trials, including more than 80,000 participants worldwide, demonstrate remarkable efficacy and low rate of serious adverse events. Based on experience with other vaccines in transplant recipients and knowing the risk of severe COVID-19 in this population, we believe that COVID-19 vaccines provide potential benefit with minimal risk. We strongly support and encourage COVID-19 vaccination of our transplant recipients. [ABSTRACT FROM AUTHOR]

Ischemia reperfusion injury (IRI) that occurs with solid organ transplantation activates the innate immune system to induce inflammation. This leads to enhanced acute allograft rejection, impaired transplant tolerance and accelerated progression of chronic rejection. In this review, we discuss the innate immune signaling pathways that have been shown to play a role in organ transplantation. In particular, we focus on Toll-like receptor signaling pathways and how they have influenced outcomes after organ transplantation both experimentally and from clinical studies. Furthermore, we describe the substances that trigger the innate immune system after transplantation and several of the key cellular mediators of inflammation. We specifically point out unique aspects of activation of the innate immune system after lung transplantation. Finally, we discuss the areas that should be investigated in the future to more clearly understand the influence of the innate immune system after organ transplantation. [ABSTRACT FROM AUTHOR]

lthough our understanding of the immunological mechanisms of transplant tolerance induction has greatly improved, how the innate immune system impacts transplant tolerance has only been recently appreciated. In this review, the involvement of the innate immune receptors, Toll-like receptors (TLRs), in both experimental models of acute allograft rejection and transplant tolerance induction in addition to clinical studies of organ transplantation are described. Several inflammatory cytokines, including IL-6, TNF-α, and type I interferons, which are induced by TLRs and other activators of innate immunity, prevent transplant tolerance induction. Their induction may be provoked by environmental exposures, such as viral or bacterial infections. Further investigation as to the innate inflammatory basis that controls the balance between immune acceptance and allograft rejection may lead us closer to the elusive goal of transplant tolerance acquisition. [ABSTRACT FROM AUTHOR]

Background: As increasing numbers of older people are listed for solid organ transplantation, there is an urgent need to better understand how aging modifies alloimmune responses. Here, we investigated whether aging impairs the ability of donor dendritic cells or recipient immunity to prime alloimmune responses to organ transplantation. Principal Findings: Using murine experimental models, we found that aging impaired the host environment to expand and activate antigen specific CD8+ T cells. Additionally, aging impaired the ability of polyclonal T cells to induce acute allograft rejection. However, the alloimmune priming capability of donor dendritic cells was preserved with aging. Conclusion: Aging impairs recipient responses, both T cell intrinsic and extrinsic, in response to organ transplantation. [ABSTRACT FROM AUTHOR]

Solid organ transplantation is a valuable therapeutic modality for a variety of end-organ diseases. The success of this therapy is largely a consequence of the development of modern immunosuppressive agents. However, these agents also lead to significant side effects that have not reduced the development of chronic rejection. Hence, modalities that induce transplantation tolerance would be of great benefit to solid organ transplant recipients. Most studies that have examined the mechanisms involved in transplantation tolerance have focused on adaptive immunity. Over the last 10 years, there has been an increasingly large appreciation of the importance of the innate immune system in immunological responses. This review will highlight recent experimental articles that investigate the role of the Toll-like receptors, which are critical innate immune receptors, in the induction of transplantation tolerance. [ABSTRACT FROM AUTHOR]

Toll like receptors (TLR) are critical innate immune receptors expressed on a variety of cells including dendritic cells that are activated by the presence of invading pathogens. However, there is emerging evidence that TLR signaling participates in inflammation that may occur in the absence of overt infection. In solid organ transplantation there is increasing evidence, both in experimental and human studies, that TLR activation is involved in the innate immune recognition of allografts. Further investigation of how innate immunity impacts solid organ transplantation may lead to improved therapies for transplant recipients. [ABSTRACT FROM AUTHOR]

Innate immunity represents the first line of defense against microbial invasion. Recent studies have determined that a group of germline-encoded receptors, termed Toll-like receptors (TLRs), are critical for recognizing foreign motifs on microbial organisms and initiating innate responses. An exciting area of research has recently linked activation of TLRs on antigen-presenting cells (APCs) to effective antigen presentation and activation of naive T cells. Most studies have shown that TLR-dependent immune function leads to T-helper 1 (TH1) immunity, although evidence also supports that TH2 immune responses may be initiated by TLR signaling in certain contexts. In either case, innate immune signaling via TLRs leads to a productive adaptive immune response. In contrast to studies in purely infectious models, emerging data from experimental and clinical studies have provided evidence that TLR immune function is important in acute allograft rejection. Specifically, MyD88, an important TLR signal adaptor, was found to be critical for the rejection of minor-mismatched skin allografts, and important for alloimmune priming and TH1 immunity against fully allogeneic skin grafts. Furthermore, a clinical study has shown that recipients with TLR 4 polymorphisms associated with endotoxin hyporesponsiveness manifest reduce acute lung allograft rejection. Collectively, these studies demonstrate that innate immunity is important for alloimmunity. Future therapeutic modalities that target innate rather than adaptive immune mechanisms represent a promising avenue for future studies in thoracic organ transplantation. [Copyright &y& Elsevier]

The article discusses the tolerance of experimental organ transplantation towards costimulatory blocking agents of t cells. It notes that the development of clinically relevant protocols for immune tolerance has resulted from the increase of patient morbidity from immunesuppression. It mentions that costimulatory blockade can provide mediation for immunological mechanisms in graft acceptance.

The article discusses how should policy-makers choose defaults regarding organ donors. First, consider that every policy must have a no-action default, and defaults impose physical, cognitive, and, in the case of donation, emotional costs on those who must change their status. Second, note that defaults can lead to two kinds of misclassification, willing donors who are not identified or people who become donors against their wishes. Changes in defaults could increase donations in the United States of additional thousands of donors a year. Because each donor can be used for about three transplants, the consequences are substantial in lives saved.

There is little insight into which patients can be weaned off right ventricular (RV) acute mechanical circulatory support (AMCS) after left ventricular assist device (LVAD) implantation. We hypothesize that concomitant RV AMCS insertion instead of postoperative implantation will improve 1-year survival and increase the likelihood of RV AMCS weaning. A multicenter retrospective database of 826 consecutive patients who received a HeartMate II or HVAD between January 2007 and December 2016 was analyzed. We identified 91 patients who had early RV AMCS on index admission. Cox proportional-hazards model was constructed to identify predictors of 1-year mortality post-RV AMCS implantation and competing risk modeling identified RV AMCS weaning predictors. There were 91 of 826 patients (11%) who required RV AMCS after CF-LVAD implantation with 51 (56%) receiving a concomitant RV AMCS and 40 (44%) implanted with a postoperative RV AMCS during their ICU stay; 48 (53%) patients were weaned from RV AMCS support. Concomitant RV AMCS with CF-LVAD insertion was associated with lower mortality (HR 0.45 [95% CI 0.26-0.80], p = 0.01) in multivariable model (which included age, BMI, angiotensin-converting enzyme inhibitor use, and heart transplantation as a time-varying covariate). In the multivariate competing risk analysis, a TPG < 12 (SHR 2.19 [95% CI 1.02-4.70], p = 0.04) and concomitant RV AMCS insertion (SHR 3.35 [95% CI 1.73-6.48], p < 0.001) were associated with a successful wean. In patients with RVF after LVAD implantation, concomitant RV AMCS insertion at the time of LVAD was associated with improved 1-year survival and increased chances of RV support weaning compared to postoperative insertion. [ABSTRACT FROM AUTHOR]

Background: Left ventricular systolic dysfunction (LVSD) accounts for almost 25% of nonacceptance of potential donor hearts. Previous smaller, single-center studies showed that LVSD following brain death may be transient, and such hearts can be successfully resuscitated with resolution of LVSD, then transplanted.Objectives: This study evaluated outcomes of donor hearts with LVSD on initial transthoracic echocardiogram (TTE) that resolved during donor management.Methods: We reviewed echocardiograms of all cardiac donors in the United Network of Organ Sharing database that were transplanted from January 1, 2007, to September 30, 2015, and identified 472 donor hearts with LVSD (left ventricular ejection fraction [LVEF] ≤40%) on initial TTE that resolved (LVEF ≥50%) during donor management on a subsequent TTE. These patients comprised the improved donor LVEF group. These were compared with donor hearts with normal LVEF (LVEF ≥55%) on the initial TTE for recipient mortality, cardiac allograft vasculopathy (CAV), and primary graft failure (PGF).Results: There was no significant difference in recipient mortality at 30 days, 1 year, 3 years, and 5 years of follow-up, nor any difference in rates of PGF at 90 days and CAV at 5 years between recipients of donor hearts with improved LVEF and recipients of donor hearts with initially normal LVEF. Post-transplant length of stay was also similar between the 2 groups. Using propensity scores, 461 transplants in the improved-donor LVEF group were matched to 461 transplants in the normal-donor LVEF group. There was no significant difference in PGF at 90 days or recipient mortality after up to 5 years of follow-up.Conclusions: In the largest analysis of donor hearts with transient LVSD, we found that such hearts can be successfully resuscitated and transplanted without increasing recipient mortality, CAV, or PGF. These results underscore the importance of appropriate donor management and should help to increase utilization of donor hearts with transient LVSD. [ABSTRACT FROM AUTHOR]

An increasing number of older people receive organ transplants for various end-stage conditions. Although organ transplantation is an effective therapy for older patients (i.e., older than 65 years of age), such as in end-stage renal disease, this therapy has not been optimized for older patients because of our lack of understanding of the effect of aging and the immune response to organ transplantation. Here, we provide an overview of the impact of aging on both the allograft and the recipient and its effect on the immune response to organ transplantation. We describe what has been determined to date, discuss existing gaps in our knowledge, and make suggestions on necessary future studies to optimize organ transplantation for older people. [ABSTRACT FROM AUTHOR]

Graft inflammation impairs the induction of solid organ transplant tolerance and enhances acute and chronic rejection. Elucidating the mechanisms by which inflammation is induced after organ transplantation could lead to novel therapeutics to improve transplant outcomes. In this Review we describe endogenous substances--damage-associated molecular patterns (DAMPs)--that are released after allograft reperfusion and induce inflammation. We also describe innate immune signalling pathways that are activated after solid organ transplantation, with a focus on Toll-like receptors (TLRs) and their signal adaptor, MYD88. Experimental and clinical studies have yielded a large body of evidence that TLRs and MYD88 are instrumental in initiating allograft inflammation and promoting the development of acute and chronic rejection. Ongoing clinical studies are testing TLR inhibition strategies in solid organ transplantation, although avoiding compromising host defence to pathogens is a key challenge. Further elucidation of the mechanisms by which sterile inflammation is induced, maintained and amplified within the allograft has the potential to lead to novel anti-inflammatory treatments that could improve outcomes for solid organ transplant recipients. [ABSTRACT FROM AUTHOR]

Institutional Affiliations: Co-chairs: Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs: Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers: Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers: Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina [Copyright &y& Elsevier]