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American Journal of Transplantation: Volume 21, Number 12, December 2021
doi : 10.1111/ajt.16058
Volume 21, Issue 12
As 2021 comes to a close, the transplantation community continues to learn from the COVID-19 pandemic, albeit having progressed from elementary to graduate school lessons. While 2020 was focused on infection, disease severity, risk factors, and outcomes, 2021 was dominated by vaccines. In this issue, we have no less than 5 articles and 3 letters delineating and/or discussing the response of transplant recipients to COVID vaccines.
COVID-19 Spurs Transplant Vaccination Policy
Lara C. Pullen PHD
doi : 10.1111/ajt.16055
Volume 21, Issue 12 p. 3817-3818
This month's installment of “The AJT Report” discusses the increasing need for and benefits of a clear vaccination policy for transplant donors and recipients. We also present our end-of-year list of recommended books for gifting and enjoying.
The xenobiotic receptor CAR directs T cell response to bile acids
Xian C. Li MD, PHD
doi : 10.1111/ajt.16056
Volume 21, Issue 12 p. 3819-3819
The xenobiotic receptor CAR plays a compartmentalized role in regulating mucosal T cells and mucosal inflammation.
Disparities persist for Black liver transplant recipients despite years of data collection: What is missing?
Nikhilesh R. Mazumder,Dinee Simpson
doi : 10.1111/ajt.16844
Volume 21, Issue 12 p. 3821-3822
Nearly 20 years ago, the implementation of the Model for End Stage Liver Disease (MELD) score was anticipated to reduce disparities in liver transplantation (LT). Prior to its rollout, Black patients with liver disease were noted to have lower listing rates and higher waitlist mortality compared to White patients.1, 2 While initial analysis did support that a transition to a MELD-based organ allocation system had reduced disparities in waitlist mortality, Black patients continued to have lower rates of listing itself.3, 4 Furthermore, the analysis of post-transplant outcomes of patients between 2002 and 2006 continued to show that Black patients had lower graft and patient survival.5 Of note, there was no difference in outcomes by race found at 1 year post-transplant—these were found at 2 years and most associated with public insurance and hepatitis C, the most common cause of liver disease in Black patients.4, 5 Since this time period, the field of transplantation has significantly changed with regard to national health-care policy, incorporation of sodium into the MELD score, organ allocation for high-MELD patients, and highly effective treatments for hepatitis C via direct-acting antivirals (DAA).
Hemophagocytic syndrome with graft-versus-host disease after liver transplantation: The bone marrow as a not so quiet battlefield?
Paul Szabolcs
doi : 10.1111/ajt.16816
Volume 21, Issue 12 p. 3823-3824
Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but horrific scenario. While it is far less common than steroid-refractory GVHD (SR-GVHD) seen after allogeneic hematopoietic stem cell transplantation (allo-HSCT), GVHD after LT is more ferocious and lethal. Even after the introduction of targeted biologicals that suppress signaling by certain pro-inflammatory cytokines such as TNF? and IL-6, infection-associated death is the final outcome in more than two-thirds of the cases with or without concomitant pancytopenia.1 This is not the case with SR-GVHD after allo-HSCT where favorable clinical responses can be documented in >50% of the cases since the introduction of JAK1/2 inhibition with ruxolitinib which became the first FDA-approved drug for treatment of SR-GVHD.2 GVHD prophylaxis after HSCT typically consists of two agents with tacrolimus most commonly combined with either methotrexate, mycophenolate, or sirolimus. Once GVHD is diagnosed with diarrhea >1 L/day or morbilliform skin rash >50% body surface prednisone will be started as first-line therapy. Ruxolitinib is the immediate next choice if prednisone taper is not feasible by 10–14 days. Survival after SR-GVHD has gradually improved >50% over the past decade with extracorporeal photopheresis, ruxolitinib, tocilizumab, and other anti-inflammatory or integrin blocking antibodies joining the repertoire of options.2 The biological reasons for the superior outcomes in the HSCT setting are still speculative and are possibly multifold. The relatively lesser degree of HLA-mismatch could play a major role in slowing the progression of immunopathology. Even haplotype mismatched allo-HSCT from a family member is performed with at least 4 of 8 HLA determinants that are not only matched but identical by high-resolution typing methods. The degree of high-resolution HLA-match is far lower with LT and most other solid organ transplantation (SOT) from unrelated donors. The anticipatory awareness in the HSCT community for the appearance of non-infectious diarrhea or morbilliform rash with or without diarrhea is high and prompts intervention within 72 h by the addition of prednisone, possibly even before diagnostic biopsy reports are finalized or serum biomarker studies reported.3 Treatment paradigms seem to also differ. Once GVHD is diagnosed after HSCT at grade 2 or higher, immunosuppression will be intensified in striking contrast with SOT where temporary withdrawal or taper of immunosuppressive therapy (IST) is commonly the first -and probably counterproductive-step. Importantly, neutropenia is rare during the first weeks of GVHD after allo-HSCT and the resultant risk for bacterial or fungal sepsis is therefore less common.
Apples, oranges, and anything in between: In search of the best desensitization therapy
Carrie A. Schinstock,Anat R. Tambur
doi : 10.1111/ajt.16808
Volume 21, Issue 12 p. 3825-3826
Patients exhibiting high percent calculated panel reactive antibodies (cPRA) have limited access to transplantation. A sliding scale prioritization scheme was introduced to the allocation system in December of 2014 to support patients with a cPRA ?98. While many highly sensitized patients benefited from the change, patients with cPRA >99.9 remain disadvantaged and may benefit from desensitization.1 Other highly sensitized patients with an HLA incompatible living donor may also benefit from combining kidney paired donation and desensitization. Thus far, several desensitization approaches have been reported, with equivocal results.
Unpacking the COVID-19 vaccine responses: Do we have what we need for a successful trip?
Lara Danziger-Isakov,Martina Sester
doi : 10.1111/ajt.16833
Volume 21, Issue 12 p. 3827-3828
The SARS-CoV-2 pandemic has upended the world and the field of transplantation. With the introduction of COVID-19 vaccines, we have entered a new phase; however, our understanding of vaccine responses and protection against infection in solid organ transplant recipients continue to evolve.
Buyer beware: The risks of donor-derived vaccine-induced thrombosis and thrombocytopenia
Cameron Wolfe,Atul Humar
doi : 10.1111/ajt.16802
Volume 21, Issue 12 p. 3829-3830
The emergence of the Sars-CoV-2 virus has posed unique challenges specific to transplantation and donation. For our transplant patients in our waiting lists, they have faced uncertainty, unsure if the pandemic will delay live-saving transplants. In March 2021, vaccine-induced thrombosis and thrombocytopenia (VITT) and central venous sinus thrombosis were recognized first in Europe with the Astra-Zeneca ChAdOx01 nCoV-19 vaccine and then in the United States with the Janssen Covid-19 Ad.26.COV2.S vaccine. Not only did this represent a new risk to describe to our patients and colleagues, but because of the life-threatening nature of this complication, we began receiving offers from donors who had died from VITT.1, 2
The potential of ex vivo lung perfusion on improving organ quality and ameliorating ischemia reperfusion injury
Jasper Iske,Christopher A. Hinze,Jawad Salman,Axel Haverich,Stefan G. Tullius,Fabio Ius
doi : 10.1111/ajt.16784
Volume 21, Issue 12 p. 3831-3839
Allogeneic lung transplantation (LuTx) is considered the treatment of choice for a broad range of advanced, progressive lung diseases resistant to conventional treatment regimens. Ischemia reperfusion injury (IRI) occurring upon reperfusion of the explanted, ischemic lung during implantation remains a crucial mediator of primary graft dysfunction (PGD) and early allo-immune responses. Ex vivo lung perfusion (EVLP) displays an advanced technique aiming at improving lung procurement and preservation. Indeed, previous clinical trials have demonstrated a reduced incidence of PGD following LuTx utilizing EVLP, while long-term outcomes are yet to be evaluated. Mechanistically, EVLP may alleviate donor lung inflammation through reconditioning the injured lung and diminishing IRI through storing the explanted lung in a non-ischemic, perfused, and ventilated status.
Examining the critical role of advanced practice providers on a multidisciplinary transplant team
Heather E. Chambers,Kristi Reinschmidt,Georgeine Smith,Eliana Agudelo,Katherine Brodahl,Emily Herriman,Haley Hoy,Kylie Pont,Ashley Seawright,Elizabeth Stearns,Ana-Marie Torres,Elaina Weldon,Daryle M. Blackstock
doi : 10.1111/ajt.16715
Volume 21, Issue 12 p. 3840-3846
It is well documented that Physician Assistants (PAs) and Nurse Practitioners (NPs), collectively known as Advanced Practice Providers (APPs), have a beneficial role beyond the field of primary care. APPs broad spectrum of knowledge make them particularly well suited for specializing in complex fields such as transplant. Variations in practice across transplant centers lead to questions regarding optimal use of APPs. Using job descriptions from transplant centers currently employing APPs, we sought to examine the critical role of transplant APPs beyond clinical care alone. In this review, we explore not only the general training of APPs and current utilization of APPs in transplant, but also safety, cost effectiveness, and comparison of APPs to other transplant providers. We aimed to highlight the importance of recruitment and retention of transplant specific trained APPs to provide continuity in transplant programs. Additionally, APPs expansion into transplant research, quality improvement, leadership, and management must be considered. We challenge transplant centers utilizing APPs to consider these important aspects when seeking ways to expand and optimize the critical role APPs provide on the transplant team.
Properties of regulatory B cells regulating B cell targets
Qiang Fu,Kang Mi Lee,Guoli Huai,Kevin Deng,Divyansh Agarwal,Charles G. Rickert,Noel Feeney,Rudy Matheson,Hongji Yang,Christian LeGuern,Shaoping Deng,James F. Markmann
doi : 10.1111/ajt.16772
Volume 21, Issue 12 p. 3847-3857
Regulatory B cells (Bregs) have shown promise as anti-rejection therapy applied to organ transplantation. However, less is known about their effect on other B cell populations that are involved in chronic graft rejection. We recently uncovered that naïve B cells, stimulated by TLR ligand agonists, converted into B cells with regulatory properties (Bregs-TLR) that prevented allograft rejection. Here, we examine the granular phenotype and regulatory properties of Breg-TLR cells suppressing B cells. Cocultures of Bregs-TLR with LPS-activated B cells showed a dose-dependent suppression of targeted B cell proliferation. Adoptive transfers of Bregs-TLR induced a decline in antibody responses to antigenically disparate skin grafts. The role of Breg BCR specificity in regulation was assessed using B cell-deficient mice replenished with transgenic BCR (OB1) and TCR (OT-II) lymphocytes of matching antigenic specificity. Results indicated that proliferation of OB1 B cells, mediated through help from CD4+ OT-II cells, was suppressed by OB1 Bregs of similar specificity. Transcriptomic analyses indicated that Bregs-TLR suppression is associated with a block in targeted B cell differentiation controlled by PRDM1 (Blimp1). This work uncovered the regulatory properties of a new brand of Breg cells and provided mechanistic insights into potential applications of Breg therapy in transplantation.
Targeting NF-?B c-Rel in regulatory T cells to treat corneal transplantation rejection
Jiang Bian,Ting Wang,Jijun Sun,Xiaozhen He,Zhijiao Wu,Songmei Zhang,Hao Chi,Tingting Fan,Shaowen Wang,Weiyun Shi,Qingguo Ruan
doi : 10.1111/ajt.16760
Volume 21, Issue 12 p. 3858-3870
The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector-like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam-Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF-?B c-Rel, a key mediator of effector T cell function, was significantly increased in inflam-Tregs. Mechanistic study revealed that elevated NF-?B c-Rel level in inflam-Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF-?B c-Rel was able to improve the immune suppressive function of inflam-Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF-?B c-Rel as a key mediator of the conversion of Tregs into effector-like cells when under inflammatory environment.
Targeting peripheral immune organs with self-assembling prodrug nanoparticles ameliorates allogeneic heart transplant rejection
Ke Zhou,Xiaona Chen,Liang Zhang,Zhentao Yang,Hai Zhu,Danjing Guo,Rong Su,Hui Chen,Hui Li,Penghong Song,Xiao Xu,Hangxiang Wang,Shusen Zheng,Haiyang Xie
doi : 10.1111/ajt.16748
Volume 21, Issue 12 p. 3871-3882
Organ transplantation has become a mainstay of therapy for patients with end-stage organ diseases. However, long-term administration of immunosuppressive agents, a scheme for improving the survival of transplant recipients, has been compromised by severe side effects and posttransplant complications. Therapeutic delivery targeting immune organs has the potential to address these unmet medical issues. Here, through screening of a small panel of mammalian target of rapamycin complex kinase inhibitor (TORKinib) compounds, a TORKinib PP242 is identified to be able to inhibit T cell function. Further chemical derivatization of PP242 using polyunsaturated fatty acids (i.e., docosahexaenoic acid) transforms this water-insoluble hydrophobic agent into a self-assembling nanoparticle (DHA-PP242 nanoparticle [DPNP]). Surface PEGylation of DPNP with amphiphilic copolymers renders the nanoparticles aqueously soluble for preclinical studies. Systemically administered DPNP shows tropism for macrophages within peripheral immune organs. Furthermore, DPNP regulates differentiation of adoptively transferred T cells in a macrophage-dependent manner in Rag1?/? mouse model. In an experimental model of heart transplantation, DPNP significantly extends the survival of grafts through inducing immune suppression, thus reducing the inflammatory response of the recipients. These findings suggest that targeted delivery of TORKinibs exploiting prodrug-assembled nanoparticle scaffolds may provide a therapeutic option against organ rejection.
Changes and mediators of survival disparity among Black liver transplant recipients in the United States
Brian P. Lee,Jennifer L. Dodge,Norah A. Terrault
doi : 10.1111/ajt.16767
Volume 21, Issue 12 p. 3883-3893
A landmark 2002 study identified Black liver transplant (LT) recipients as having lower post-LT survival compared to other races. While persistent disparities exist, changes over time and mediating factors are understudied. Capturing LT recipients between 2002 and 2018 in UNOS, we used logistic regression and Cox proportional-hazard models to calculate differences in post-LT mortality among races. We examined interactions between transplant year and race. A mediation analysis assessed biologic and environmental factors potentially associated with race differences in post-LT survival. The cohort included 46,997 LT recipients (3898 Black;36,560 White;6539 Hispanic). In most years, Black (vs. White) LT recipients had a higher probability of age-adjusted mortality, not observed among Hispanics. In multivariable analysis, Blacks (vs. Whites) had higher (aHR = 1.15, 95% CI 1.07–1.24), whereas Hispanics had lower (aHR = 0.78, 95% CI 0.72–0.83) risk of mortality. Differences in post-LT mortality among Blacks (vs. Whites) narrowed between 2002 and 2009, were similar between 2010 and 2013, and may have worsened between 2014 and 2018. Race differences were larger for mortality beyond 1-year post-LT (vs. within 1-year), and among non-HCV (vs. HCV). Alcohol-associated liver disease (ALD) was the strongest mediator (13.9%, 95% CI 8.7–32.7%) of the Black–White disparity in 2010–2018. Our analyses suggest disparities may worsen with longer follow-up, as HCV recedes with elimination efforts, and with further increases in ALD.
Graft-versus-host disease after liver transplantation is associated with bone marrow failure, hemophagocytosis, and DNMT3A mutations
Laura F. Newell,Jennifer Dunlap,Ken Gatter,Grover C. Bagby,Richard D. Press,Rachel J. Cook,Luke Fletcher,Jessica T. Leonard,Kelli M. Leong,Joseph S. Bubalo,Ali Olyaei,Thomas G. Deloughery,Richard T. Maziarz,Erin Maynard,Susan L. Orloff,C. Kristian Enestvedt
doi : 10.1111/ajt.16635
Volume 21, Issue 12 p. 3894-3906
Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.
Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients
Christian Kjellman,Angela Q. Maldonado,Kristoffer Sjöholm,Bonnie E. Lonze,Robert A. Montgomery,Anna Runström,Tomas Lorant,Niraj M. Desai,Christophe Legendre,Torbjörn Lundgren,Bengt von Zur Mühlen,Ashley A. Vo,Håkan Olsson,Stanley C. Jordan
doi : 10.1111/ajt.16754
Volume 21, Issue 12 p. 3907-3918
Imlifidase is a cysteine proteinase which specifically cleaves IgG, inhibiting Fc-mediated effector function within hours of administration. Imlifidase converts a positive crossmatch to a potential donor (T cell, B cell, or both), to negative, enabling transplantation to occur between previously HLA incompatible donor-recipient pairs. To date, 39 crossmatch positive patients received imlifidase prior to a kidney transplant in four single-arm, open-label, phase 2 studies. At 3 years, for patients who were AMR+ compared to AMR?, death-censored allograft survival was 93% vs 77%, patient survival was 85% vs 94%, and mean eGFR was 49 ml/min/1.73 m2 vs 61 ml/min/1.73 m2, respectively. The incidence of AMR was 38% with most episodes occurring within the first month post-transplantation. Sub-analysis of patients deemed highly sensitized with cPRA ? 99.9%, and unlikely to be transplanted who received crossmatch-positive, deceased donor transplants had similar rates of patient survival, graft survival, and eGFR but a higher rate of AMR. These data demonstrate that outcomes and safety up to 3 years in recipients of imlifidase-enabled allografts is comparable to outcomes in other highly sensitized patients undergoing HLA-incompatible transplantation. Thus, imlifidase is a potent option to facilitate transplantation among patients who have a significant immunologic barrier to successful kidney transplantation.
Liver transplantation from active COVID-19 donors: A lifesaving opportunity worth grasping?
Renato Romagnoli,Salvatore Gruttadauria,Giuseppe Tisone,Giuseppe Maria Ettorre,Luciano De Carlis,Silvia Martini,Francesco Tandoi,Silvia Trapani,Margherita Saracco,Angelo Luca,Tommaso Maria Manzia,Ubaldo Visco Comandini,Riccardo De Carlis,Valeria Ghisetti,Rossana Cavallo,Massimo Cardillo,Paolo Antonio Grossi
doi : 10.1111/ajt.16823
Volume 21, Issue 12 p. 3919-3925
COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors’ liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool.
Humoral response to SARS-CoV-2 is well preserved and symptom dependent in kidney transplant recipients
Maria Magicova,Martina Fialova,Ivan Zahradka,Silvie Rajnochova-Bloudickova,David Hackajlo,Petr Raska,Ilja Striz,Ondrej Viklicky
doi : 10.1111/ajt.16746
Volume 21, Issue 12 p. 3926-3935
Data on the immune response to SARS-CoV-2 in kidney transplant recipients are scarce. Thus, we conducted a single-center observational study to assess the anti-SARS-CoV-2 IgG seroprevalence in outpatient kidney transplant recipients (KTR; n = 1037) and healthcare workers (HCW; n = 512) during the second wave of the COVID-19 pandemic in fall 2020 and evaluated the clinical variables affecting antibody levels. Antibodies against S1 and S2 subunit of SARS-CoV-2 were evaluated using immunochemiluminescent assay (cut off 9.5 AU/ml, sensitivity of 91.2% and specificity of 90.2%). Anti-SARS-CoV-2 IgG seroprevalence was lower in KTR than in HCW (7% vs. 11.9%, p = .001). Kidney transplant recipients with SARS-CoV-2 infection were younger (p = .001) and received CNI-based immunosuppression more frequently (p = .029) than seronegative KTR. Anti-SARS-CoV-2 IgG positive symptomatic KTR had a higher BMI (p = .04) than asymptomatic KTR. Interestingly, anti-SARS-CoV-2 IgG levels were higher in KTR than in HCW (median 31 AU/ml, IQR 17–84 vs. median 15 AU/ml, IQR 11–39, p < .001). The presence of moderate to severe symptoms in KTR was found to be the only independent factor affecting IgG levels (Beta coefficient = 41.99, 95% CI 9.92–74.06, p = .011) in the multivariable model. In conclusion, KTR exhibit a well-preserved symptom-dependent humoral response to SARS-CoV-2 infection.
A systematic review and meta-analysis of COVID-19 in kidney transplant recipients: Lessons to be learned
Daan Kremer,Tobias T. Pieters,Marianne C. Verhaar,Stefan P. Berger,Stephan J. L. Bakker,Arjan D. van Zuilen,Jaap A. Joles,Robin W. M. Vernooij,Bas W. M. van Balkom
doi : 10.1111/ajt.16742
Volume 21, Issue 12 p. 3936-3945
Kidney transplant recipients (KTR) may be at increased risk of adverse COVID-19 outcomes, due to prevalent comorbidities and immunosuppressed status. Given the global differences in COVID-19 policies and treatments, a robust assessment of all evidence is necessary to evaluate the clinical course of COVID-19 in KTR. Studies on mortality and acute kidney injury (AKI) in KTR in the World Health Organization COVID-19 database were systematically reviewed. We selected studies published between March 2020 and January 18th 2021, including at least five KTR with COVID-19. Random-effects meta-analyses were performed to calculate overall proportions, including 95% confidence intervals (95% CI). Subgroup analyses were performed on time of submission, geographical region, sex, age, time after transplantation, comorbidities, and treatments. We included 74 studies with 5559 KTR with COVID-19 (64.0% males, mean age 58.2 years, mean 73 months after transplantation) in total. The risk of mortality, 23% (95% CI: 21%–27%), and AKI, 50% (95% CI: 44%–56%), is high among KTR with COVID-19, regardless of sex, age and comorbidities, underlining the call to accelerate vaccination programs for KTR. Given the suboptimal reporting across the identified studies, we urge researchers to consistently report anthropometrics, kidney function at baseline and discharge, (changes in) immunosuppressive therapy, AKI, and renal outcome among KTR.
Circulatory follicular helper T lymphocytes associate with lower incidence of CMV infection in kidney transplant recipients
Patricia Suàrez-Fernández,Alberto Utrero-Rico,Virginia Sandonis,Estéfani García-Ríos,Daniel Arroyo-Sánchez,Mario Fernández-Ruiz,Amado Andrés,Natalia Polanco,Cecilia González-Cuadrado,Patricia Almendro-Vázquez,Pilar Pérez-Romero,José María Aguado,Estela Paz-Artal,Rocío Laguna-Goya
doi : 10.1111/ajt.16725
Volume 21, Issue 12 p. 3946-3957
Primary infection and/or reactivation of cytomegalovirus (CMV) in kidney transplant recipients (KTR) favor rejection and mortality. T follicular helper cells (TFH) could contribute to protection against CMV. Circulatory TFH (cTFH) were studied pretransplant and early posttransplant in 90 CMV seropositive KTR not receiving antithymocyte globulin or antiviral prophylaxis, followed-up for 1 year. Patients who presented CMV infection had significantly lower cTFH and activated cTFH pretransplant and early posttransplant. Pretransplant activated cTFH were also lower within patients who developed CMV disease. Pre- and 14 days posttransplant activated cTFH were an independent protective factor for CMV infection (HR 0.41, p = .01; and 0.52, p = .02, respectively). KTR with low cTFH 7 days posttransplant (<11.9%) had lower CMV infection-free survival than patients with high cTFH (28.2% vs. 67.6%, p = .002). cTFH were associated with CMV-specific neutralizing antibodies (Nabs). In addition, IL-21 increased interferon-? secretion by CMV-specific CD8+ T cells in healthy controls. Thus, we show an association between cTFH and lower incidence of CMV infection, probably through their cooperation in CMV-specific Nab production and IL-21-mediated enhancement of CD8+ T cell activity. Moreover, monitoring cTFH pre- and early posttransplant could improve CMV risk stratification and help select KTR catalogued at low/intermediate risk who could benefit from prophylaxis.
Cytomegalovirus transmission in mismatched solid organ transplant recipients: Are factors other than anti-viral prophylaxis at play?
Cristina Hernandez,Curtis Mabilangan,Catherine Burton,Karen Doucette,Jutta Preiksaitis
doi : 10.1111/ajt.16734
Volume 21, Issue 12 p. 3958-3970
Although antiviral prophylaxis has reduced cytomegalovirus (CMV) DNAemia and disease in seronegative solid organ transplant (SOT) recipients (R-) receiving seropositive donor organs (D+), its impact on CMV transmission is uncertain. Transmission, defined as CMV antigenemia/CMV DNAemia and/or seroconversion by year 2, and associated demographic risk factors were studied retrospectively in 428 D+/R- and 429 D-/R- patients receiving a SOT at our center. The cumulative transmission incidence was higher for lung (90.5%) and liver recipients (85.1%) than heart (72.7%), kidney (63.9%), and pancreas (56.2%) recipients (p < .001) and was significantly lower in living (50.1%) versus deceased donor (77.4%, p < .001) kidney recipients despite identical antiviral prophylaxis. In multivariate analysis, only allograft type predicted transmission risk (HR [CI] lung 1.609 [1.159, 2.234] and liver 1.644 [1.209, 2.234] vs kidney). For 53 D+ donating to >1 R- with adequate follow-up, 43 transmitted to all, three transmitted to none, and seven transmitted inconsistently with lungs and livers always transmitting but donor-matched heart, kidney or kidney-pancreas allografts sometimes not. Kidney pairs transmitted concordantly. CMV transmission risk is allograft-specific and unchanged despite antiviral prophylaxis. Tracking transmission and defining donor factors associated with transmission escape may provide novel opportunities for more targeted CMV prevention and improve outcome analysis in antiviral and vaccine trials.
Cellular and humoral immune response after mRNA-1273 SARS-CoV-2 vaccine in liver and heart transplant recipients
Sabina Herrera,Jordi Colmenero,Mariona Pascal,Miguel Escobedo,María A. Castel,Eduard Sole-González,Eduard Palou,Natalia Egri,Pablo Ruiz,Mar Mosquera,Asunción Moreno,Manel Juan,Anna Vilella,Alex Soriano,Marta Farrero,Marta Bodro
doi : 10.1111/ajt.16768
Volume 21, Issue 12 p. 3971-3979
Recently published studies have found an impaired immune response after SARS-CoV-2 vaccination in solid organ recipients. However, most of these studies have not assessed immune cellular responses in liver and heart transplant recipients. We prospectively studied heart and liver transplant recipients eligible for SARS-CoV-2 vaccination. Patients with past history of SARS-CoV-2 infection or SARS-CoV-2 detectable antibodies (IgM or IgG) were excluded. We assessed IgM/IgG antibodies and ELISpot against the S protein 4 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. Side effects, troponin I, liver tests and anti-HLA donor-specific antibodies (DSA) were also assessed. A total of 58 liver and 46 heart recipients received two doses of mRNA-1273 vaccine. Median time from transplantation to vaccination was 5.4 years (IQR 0.3–27). Sixty-four percent of the patients developed SARS-CoV-2 IgM/IgG antibodies and 79% S-ELISpot positivity. Ninety percent of recipients developed either humoral or cellular response (87% in heart recipients and 93% in liver recipients). Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation. Local and systemic side effects were mild or moderate, and none presented DSA or graft dysfunction after vaccination. Ninety percent of our patients did develop humoral or cellular responses to mRNA-1273 vaccine. Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation, highlighting the need to further protect these patients.
Humoral and cellular immune response and safety of two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients
Victoria G. Hall,Victor H. Ferreira,Matthew Ierullo,Terrance Ku,Tina Marinelli,Beata Majchrzak-Kita,Anila Yousuf,Vathany Kulasingam,Atul Humar,Deepali Kumar
doi : 10.1111/ajt.16766
Volume 21, Issue 12 p. 3980-3989
Solid organ transplant recipients are at high risk of severe disease from COVID-19. We assessed the immunogenicity of mRNA-1273 vaccine using a combination of antibody testing, surrogate neutralization assays, and T cell assays. Patients were immunized with two doses of vaccine and immunogenicity assessed after each dose using the above tests. CD4+ and CD8+ T cell responses were assessed in a subset using flow-cytometry. A total of 127 patients were enrolled of which 110 provided serum at all time points. A positive anti-RBD antibody was seen in 5.0% after one dose and 34.5% after two doses. Neutralizing antibody was present in 26.9%. Of note, 28.5% of patients with anti-RBD did not have neutralizing antibody. T cell responses in a sub-cohort of 48 patients showed a positive CD4+ T cell response in 47.9%. Of note, in this sub-cohort, 46.2% of patients with a negative anti-RBD, still had a positive CD4+ T cell response. The vaccine was safe and well-tolerated. In summary, immunogenicity of mRNA-1273 COVID-19 vaccine was modest, but a subset of patients still develop neutralizing antibody and CD4+T- cell responses. Importantly polyfunctional CD4+T cell responses were observed in a significant portion who were antibody negative, further highlighting the importance of vaccination in this patient population.
Cellular immunity predominates over humoral immunity after homologous and heterologous mRNA and vector-based COVID-19 vaccine regimens in solid organ transplant recipients
Tina Schmidt,Verena Klemis,David Schub,Sophie Schneitler,Matthias C. Reichert,Heinrike Wilkens,Urban Sester,Martina Sester,Janine Mihm
doi : 10.1111/ajt.16818
Volume 21, Issue 12 p. 3990-4002
Knowledge on the immunogenicity of vector-based and mRNA-vaccines in solid organ transplant recipients is limited. Therefore, SARS-CoV-2–specific T cells and antibodies were analyzed in 40 transplant recipients and 70 controls after homologous or heterologous vaccine-regimens. Plasmablasts and SARS-CoV-2–specific CD4 and CD8 T cells were quantified using flow cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. The two vaccine types differed after the first vaccination, as IgG and neutralizing activity were more pronounced after mRNA priming (p = .0001 each), whereas CD4 and CD8 T cell levels were higher after vector priming (p = .009; p = .0001). All regimens were well tolerated, and SARS-CoV-2–specific antibodies and/or T cells after second vaccination were induced in 100% of controls and 70.6% of transplant recipients. Although antibody and T cell levels were lower in patients, heterologous vaccination led to the most pronounced induction of antibodies and CD4 T cells. Plasmablast numbers were significantly higher in controls and correlated with SARS-CoV-2–specific IgG- and T cell levels. While antibodies were only detected in 35.3% of patients, cellular immunity was more frequently found (64.7%) indicating that assessment of antibodies is insufficient to identify COVID-19-vaccine responders. In conclusion, heterologous vaccination seems promising in transplant recipients, and combined analysis of humoral and cellular immunity improves the identification of responders among immunocompromised individuals.
Critical care and ventilatory management of deceased organ donors impact lung use and recipient graft survival
Elizabeth A. Swanson,Madhukar S. Patel,Michael P. Hutchens,Claus U. Niemann,Tahnee Groat,Darren J. Malinoski,Mitchell B. Sally
doi : 10.1111/ajt.16719
Volume 21, Issue 12 p. 4003-4011
Current risk-adjusted models for donor lung use and lung graft survival do not include donor critical care data. We sought to identify modifiable donor physiologic and mechanical ventilation parameters that predict donor lung use and lung graft survival. This is a prospective observational study of donors after brain death (DBDs) managed by 19 Organ Procurement Organizations from 2016 to 2019. Demographics, mechanical ventilation parameters, and critical care data were recorded at standardized time points during donor management. The lungs were transplanted from 1811 (30%) of 6052 DBDs. Achieving ?7 critical care endpoints was a positive predictor of donor lung use. After controlling for recipient factors, donor blood pH positively predicted lung graft survival (OR 1.48 per 0.1 unit increase in pH) and the administration of dopamine during donor management negatively predicted lung graft survival (OR 0.19). Tidal volumes ?8 ml/kg predicted body weight (OR 0.65), and higher positive end-expiratory pressures (OR 0.91 per cm H2O) predicted decreased donor lung use without affecting lung graft survival. A randomized clinical trial is needed to inform optimal ventilator management strategies in DBDs.
Effects of broader geographic distribution of donor lungs on travel mode and estimated costs of organ procurement
Carli J. Lehr,Melissa A. Skeans,Erika D. Lease,Maryam Valapour
doi : 10.1111/ajt.16697
Volume 21, Issue 12 p. 4012-4022
On November 24, 2017, US lung transplant policy replaced donor service area with 250-nautical-mile radius as the first unit of allocation. Understanding this policy's economic impact is important, because the United States is poised to adopt the broadest feasible geographic organ distribution. All lung transplant recipients from January 1, 2015, to December 31, 2018, in the Scientific Registry of Transplant Recipients, were included. Recipients before and after November 24, 2017 were in the donor service area-first and 250-nautical-mile donor service area-free periods, respectively. Travel time was estimated using a Google application; mode was assigned as flying when driving time was longer than 60 min. Travel costs were estimated by mode and distance. Travel distance and time for organ procurement increased under the policy change. The estimated proportion of organs traveling by air increased from 61% to 76%. Estimated average costs increased by $14 051 if travel mode changed to flying, resulting in an average increase of $1264 for all transplants. Travel costs were highest for candidates <18 years and adults with high lung allocation scores. Broader geographic distribution increased estimated organ procurement costs for a small percentage of lung transplants. Further analysis should elucidate the broad economic impact of such policies.
Comparing outcomes of third and fourth kidney transplantation in older and younger patients
Shaifali Sandal,JiYoon B. Ahn,Dorry L. Segev,Marcelo Cantarovich,Mara A. McAdams-DeMarco
doi : 10.1111/ajt.16786
Volume 21, Issue 12 p. 4023-4031
Performing third or fourth kidney transplantation (3KT and 4KT) in older patients is rare due to surgical and immunologic challenges. We aimed to analyze and compare the outcomes of younger (18–64 years) and older (?65 years) recipients of 3KT and 4KT. Between 1990 and 2016, we identified 5816 recipients of 3KTs (153 were older) and 886 recipients of 4KTs (18 were older). The incidences of delayed graft function (24.3% vs. 24.8%, p = .89), primary non-function (3.2% vs. 1.3%, p = .21), 1-year acute rejection (18.6% vs. 14.8%, p = .24), and 5-year death censored graft failure (DCGF) (24.8% vs. 17.9%, p = .06) were not different between younger and older recipients of 3KT. However, 5-year mortality was higher in older recipients (14.0% vs. 33.8%, p < .001) which remained significant after adjustment (aHR = 3.21, 95% CI: 2.59–3.99). Similar patterns were noted in the 4KT cohort. When compared with waitlisted patients, 3KT and 4KT are associated with a lower risk of mortality; aHR = 0.37, 95% CI: 0.33–0.41 and aHR = 0.31, 95% CI: 0.24–0.41, respectively. This survival benefit did not differ by recipient age (younger vs. older, p for interaction = 3KT: .49 and 4KT: .58). In the largest cohort described to date, we report that there is a survival benefit of 3KT and 4KT even among older patients. Although a highly selected cohort, our results support improving access to 3KT and 4KT.
Kidney allograft biopsy findings after COVID-19
Emily Daniel,Miroslav Sekulic,Satoru Kudose,Christine Kubin,Xiaoyi Ye,Katayoon Shayan,Ankita Patel,David J. Cohen,Lloyd E. Ratner,Dominick Santoriello,M. Barry Stokes,Glen S. Markowitz,Marcus R. Pereira,Vivette D. D’Agati,Ibrahim Batal
doi : 10.1111/ajt.16804
Volume 21, Issue 12 p. 4032-4042
COVID-19 has been associated with acute kidney injury and published reports of native kidney biopsies have reported diverse pathologies. Case series directed specifically to kidney allograft biopsy findings in the setting of COVID-19 are lacking. We evaluated 18 kidney transplant recipients who were infected with SARS-CoV-2 and underwent allograft biopsy. Patients had a median age of 55 years, six were female, and five were Black. Fifteen patients developed COVID-19 pneumonia, of which five required mechanical ventilation. Notably, five of 11 (45%) biopsies obtained within 1 month of positive SARS-CoV-2 PCR showed acute rejection (four with arteritis, three of which were not associated with reduced immunosuppression). The remaining six biopsies revealed podocytopathy (n = 2, collapsing glomerulopathy and lupus podocytopathy), acute tubular injury (n = 2), infarction (n = 1), and transplant glomerulopathy (n = 1). Biopsies performed >1 month after positive SARS-CoV-2 PCR revealed collapsing glomerulopathy (n = 1), acute tubular injury (n = 1), and nonspecific histologic findings (n = 5). No direct viral infection of the kidney allograft was detected by immunohistochemistry, in situ hybridization, or electron microscopy. On follow-up, two patients died and most patients showed persistent allograft dysfunction. In conclusion, we demonstrate diverse causes of kidney allograft dysfunction after COVID-19, the most common being acute rejection with arteritis.
Weak antibody response to three doses of mRNA vaccine in kidney transplant recipients treated with belatacept
Nathalie Chavarot,Antoine Morel,Marianne Leruez-Ville,Estelle Vilain,Gillian Divard,Carole Burger,Alexandra Serris,Rebecca Sberro-Soussan,Frank Martinez,Lucile Amrouche,Lynda Bererhi,Fanny Lanternier,Christophe Legendre,Julien Zuber,Dany Anglicheau,Anne Scemla
doi : 10.1111/ajt.16814
Volume 21, Issue 12 p. 4043-4051
Poor responses to mRNA COVID-19 vaccine have been reported after 2 vaccine injections in kidney transplant recipients (KTRs) treated with belatacept. We analyzed the humoral response in belatacept-treated KTRs without a history of SARS-CoV-2 infection who received three injections of BNT162b2-mRNA COVID-19 vaccine. We also investigated vaccine immunogenicity in belatacept-treated KTRs with prior COVID-19 and characterized symptomatic COVID-19 infections after the vaccine in belatacept-treated KTRs. Among the 62 belatacept-treated KTRs (36 [58%] males), the median age (63.5 years IQR [51–72]), without COVID-19 history, only four patients (6.4%) developed anti-SARS-CoV-2 IgG with low antibody titers (median 209, IQR [20–409] AU/ml). 71% were treated with mycophenolic acid and 100% with steroids in association with belatacept. In contrast, in all the 5 KTRs with prior COVID-19 history, mRNA vaccine induced a strong antibody response with high antibody titers (median 10 769 AU/ml, IQR [6410–20 069]) after two injections. Seroprevalence after three-vaccine doses in 35 non-belatacept-treated KTRs was 37.1%. Twelve KTRs developed symptomatic COVID-19 after vaccination, including severe forms (50% of mortality). Breakthrough COVID-19 occurred in 5% of fully vaccinated patients. Administration of a third dose of BNT162b2 mRNA COVID-19 vaccine did not improve immunogenicity in KTRs treated with belatacept without prior COVID-19. Other strategies aiming to improve patient protection are needed.
Transplant trends in Mexico during the COVID-19 pandemic: Disparities within healthcare sectors
Maximiliano Servin-Rojas,Antonio Olivas-Martinez,Fernando Ramirez Del Val,Armando Torres-Gomez,Luis Navarro-Vargas,Ignacio García-Juárez
doi : 10.1111/ajt.16801
Volume 21, Issue 12 p. 4052-4060
Healthcare systems worldwide were challenged during the COVID-19 pandemic. In Mexico, the public hospitals that perform most transplants were adapted to provide care for COVID-19 patients. Using a nationwide database, we describe the first report of the impact of COVID-19 and related transplantation healthcare policies in a middle-income country by comparing statistics before and during the pandemic (pre-COVID: March 2019–February 2020 vs. COVID era: March 2020–February 2021) and by type of institution (public vs. private). The global reduction in transplantation was higher in public institutions compared with private institutions, 89% versus 62%, respectively, p < .001. When analyzing by organ, kidney transplantation decreased by 89% at public versus 57% at private, p < .001; cornea by 88% at public versus 64% at private, p < .001; liver by 88% at public versus 35% at private, p < .001; and heart by 88% in public versus 67% at private institutions, p = .4. The COVID-19 pandemic along with the implemented health policies were associated with a decrease in donations, waiting list additions, and a decrease in transplantation, particularly at public institutions, which care for the most vulnerable.
Primary hyperoxaluria diagnosed after kidney transplant: A review of the literature and case report of aggressive renal replacement therapy and lumasiran to prevent allograft loss
Hillarey K. Stone,Katherine VandenHeuvel,Alexander Bondoc,Francisco X. Flores,David K. Hooper,Charles D. Varnell Jr
doi : 10.1111/ajt.16762
Volume 21, Issue 12 p. 4061-4067
Primary hyperoxaluria type 1 is a rare inherited disorder caused by abnormal liver glyoxalate metabolism leading to overproduction of oxalate, progressive kidney disease, and systemic oxalosis. While the disorder typically presents with nephrocalcinosis, recurrent nephrolithiasis, and/or early chronic kidney disease, the diagnosis is occasionally missed until it recurs after kidney transplant. Allograft outcomes in these cases are typically very poor, often with early graft loss. Here we present the case of a child diagnosed with primary hyperoxaluria type 1 after kidney transplant who was able to maintain kidney function, thanks to aggressive renal replacement therapy as well as initiation of a new targeted therapy for this disease. This case highlights the importance of having a high index of suspicion for primary hyperoxaluria in patients with chronic kidney disease and nephrocalcinosis/nephrolithiasis or with end stage kidney disease of uncertain etiology, as initiating therapies early on may prevent poor outcomes.
Posttransplant proteinuria due to Apolipoprotein E2 deposition in a kidney allograft
Madhuri Ramakrishnan,Timothy Fields,Da Zhang,Itunu O. Owoyemi,Aditi Gupta,Jeffrey A. Klein,Nicholas S. Herrera,Mallika Gupta,Diane M. Cibrik
doi : 10.1111/ajt.16774
Volume 21, Issue 12 p. 4068-4072
Lipoprotein deposition disorders limited to the kidney and causing proteinuria are rare. We present a case of nephrotic range proteinuria presenting within 4 months after deceased donor renal transplantation in a patient with end-stage kidney disease presumed secondary to hypertension. Two transplant kidney biopsies were performed sixteen weeks after transplantation, and one year after the first biopsy, both showing lipoprotein deposits in the glomeruli, progressive focal segmental glomerulosclerosis, and effacement of visceral foot processes. The patient had a normal lipid profile. Based on previous case reports of Apolipoprotein E variants causing proteinuria in native kidneys, Apolipoprotein E genotyping was performed. Genotyping showed Apolipoprotein E2 homozygosity. This Apolipoprotein E variant has been associated with lipoprotein deposition, proteinuria, and progressive kidney disease in the native kidneys. However, this is the first case of Apolipoprotein E2 homozygosity-related kidney disease in a transplant recipient. The patient was treated with fenofibrate, angiotensin enzyme inhibition, and angiotensin receptor blockade with reduction in proteinuria, and he kept good stable kidney function.
Lung donation following SARS-CoV-2 infection
Melissa Querrey,Chitaru Kurihara,Adwaiy Manerikar,Rafael Garza-Castillon,Jeffrey Lysne,Rade Tomic,GR Scott Budinger,Samuel Kim,Kalvin Lung,Anjana Yeldandi,Ankit Bharat
doi : 10.1111/ajt.16777
Volume 21, Issue 12 p. 4073-4078
There have been over 177 million cases of COVID-19 worldwide, many of whom could be organ donors. Concomitantly, there is an anticipated increase in the need for donor lungs due to expanding indications. Given that the respiratory tract is most commonly affected by COVID-19, there is an urgent need to develop donor assessment criteria while demonstrating safety and “efficacy” of lung donation following COVID-19 infection. Accordingly, we report an intentional transplant using lungs from a donor with recent, microbiologically confirmed, COVID-19 infection into a recipient suffering from COVID-19 induced ARDS and pulmonary fibrosis. In addition to the standard clinical assays, both donor and recipient lungs were analyzed using RNAscope, which confirmed that tissues were negative for SARS-CoV-2. Immunohistochemistry demonstrated colocalized KRT17+ basaloid-like epithelium and COL1A1+ fibroblasts, a marker suggestive of lung fibrosis in COVID-19 associated lung disease, in the explanted recipient lungs but absent in the donor lungs. We demonstrate that following a thorough assessment, lung donation following resolved COVID-19 infection is safe and feasible.
Pediatric living donor intestine transplant following an atypical complication of COVID-19: A unique case report from India
Gaurav Chaubal,Hunaid Hatimi,Aditya Nanavati,Apoorv Deshpande,Parmanand Andankar,Vishnu Biradar,Parijat Gupte,Pavan Hanchnale,Suryabhan Bhalerao,Shrinivas Tambe
doi : 10.1111/ajt.16798
Volume 21, Issue 12 p. 4079-4083
Coronavirus disease-19 (COVID-19) infection causing severe gastrointestinal complications is rare. A 9-year-old child after recovering from mild COVID-19 infection developed small bowel gangrene due to superior mesenteric artery thrombosis. He required resection of entire necrotic small bowel along with caecum causing ultra-short bowel syndrome. Reverse transcriptase-polymerase chain reaction (RT-PCR) done on the resected specimen was positive for COVID-19. He was maintained on individualized parenteral nutrition for 3 months. A living donor intestinal transplant was performed using 200 cm of ileum donated by the patient's father. The graft function was satisfactory and was not complicated with thrombosis, infection, reactivation of latent COVID-19 or rejection. He could be weaned off completely from parenteral nutrition by postoperative day 21. The donor had an uneventful recovery. Six month follow-up was satisfactory with the child achieving complete enteral autonomy as well as target goal nutrition. Thrombotic phenomena associated with COVID-19 infection can affect larger vessel-like superior mesenteric artery leading to small bowel gangrene. Intestine transplant could be done safely after 3 months of recovery from COVID-19 without any adverse outcomes. Further studies are required to establish optimal timing and safety of small bowel transplant in this situation.
Binge drinking among adults, by select characteristics and state — United States, 2018
Michele K. Bohm,Yong Liu,Marissa B. Esser,Jessica B. Mesnick,Hua Lu,Yi Pan,Kurt J. Greenlund
doi : 10.1111/ajt.16057
Volume 21, Issue 12 p. 4084-4091
This article describes the prevalence, frequency, and intensity of binge alcohol drinking among US adults. Prevalence was highest among adults aged 25-34 years old, men, non-Hispanic whites, those with higher income levels, and those with a college degree. This report highlights the potential demographic shifts that may be reflected in the increasing practice of liver transplantation for acute alcohol-related hepatitis.
Hematochezia: A late complication after pancreas transplantation
Catherine Zatorski,Patty T. Liu,Michael J. Moritz,Christine Du
doi : 10.1111/ajt.16745
Volume 21, Issue 12 p. 4092-4094
Organ transplantation from deceased donors with vaccine-induced thrombosis and thrombocytopenia
UK Donor VITT Transplant Study Group,George H. B. Greenhall,Ines Ushiro-Lumb,Sue Pavord,Ian Currie,M. Thamara P. R. Perera,Hermien Hartog,Quentin A. Hill,Ismail Mohamed,Muhammad A. Khurram,Reza Motallebzadeh,Gareth Jones,Aileen Marshall,Joerg-Matthias Pollok,Nicholas Torpey,Gavin J. Pettigrew,Sanjay Mehra,Hemant Sharma,Francis Calder,Nicos Kessaris,Jay Nath,Debabrata Roy,Gabriel C. Oniscu,Marc Clancy,Karthik Santhanakrishnan,Jorge Mascaro,Sern Lim,Marius Berman,Sue Madden,Lisa Mumford,Darius Mirza,Chris Watson,Olive McGowan,Douglas Thorburn,Rommel Ravanan,Beverley J. Hunt,Chris J. Callaghan,David J. Roberts,John Forsythe
doi : 10.1111/ajt.16735
Volume 21, Issue 12 p. 4095-4097
Solid organ procurement and transplantation from deceased donors with vaccine-induced thrombosis and thrombocytopenia
Alexandre Loupy,Valentin Goutaudier,Christian Jacquelinet,François Kerbaul
doi : 10.1111/ajt.16751
Volume 21, Issue 12 p. 4098-4101
COVID-19 after two doses of mRNA vaccines in kidney transplant recipients
Rajil B. Mehta,Fernanda P. Silveira
doi : 10.1111/ajt.16778
Volume 21, Issue 12 p. 4102-4104
SARS-CoV-2 vaccine effectiveness trumps immunogenicity in solid organ transplant recipients
Sherif B. Mossad
doi : 10.1111/ajt.16744
Volume 21, Issue 12 p. 4105-4105
Response to “SARS-CoV-2 vaccine effectiveness trumps immunogenicity in solid organ transplant recipients”
Maricar Malinis,Elizabeth Cohen,Marwan M. Azar
doi : 10.1111/ajt.16770
Volume 21, Issue 12 p. 4106-4107
