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American Journal of Transplantation: Volume 21, Number 7, July 2021
doi : 10.1111/ajt.16038
Volume 21, Issue 7
2021 marks the 30th anniversary Banff Conferences on Allograft Pathology, which has provided worldwide standards for the interpretation of allograft biopsies. One momentous milestone, the first detailed classification of antibody-mediated rejection in kidney transplantation, was achieved 10 years later in 2001 as a result of “lively and in-depth discussions.”* Over the ensuing 20 years, this classification has undergone multiple and significant iterations driven by emerging data. Callemeyn and colleagues (page 2413), utilizing a decade-long cohort of both protocol and clinically indicated allograft biopsies, crystallize the ramifications of this “punctuated disequilibrium.” They quantify the impact of the changes in diagnostic classification of antibody-mediated rejection from Banff 2013 to Banff 2017 and compare allograft survival, identifying inferior prognostic accuracy for the 2017 classification scheme. This study raises many provocative questions, perhaps the most important of which is whether the purpose of Banff classification is diagnosis or risk stratification, as discussed by Mengel and Mannon (page 2321). *Racusen LC, Colvin RB, Solez K, et al. Antibody-mediated rejection criteria – an addition to the Banff ’97 classification of renal allograft rejection. Am J Transplant. 2003;3(6):708–714.
Bringing palliative care to transplant
Lara C. Pullen PHD
doi : 10.1111/ajt.16035
Volume 21, Issue 7 p. 2315-2316
This month's installment of “The AJT Report” discusses the issue of palliative care and how it can be integrated into the care of transplant candidates and patients to improve quality of life. We also report on a recently proposed bill designed to remove critical barriers to liver donation in the U.S.
Taking AIM2 at regulatory T cells to modulate autoimmune diseases
Xian C. Li MD, PHD
doi : 10.1111/ajt.16036
Volume 21, Issue 7 p. 2317-2317
AIM2 safeguards Treg stability by suppressing the Akt-mTOR pathway via the protein phosphatase PP2A.
Semi-direct alloantigen presentation detected in human liver but not kidney transplant recipients: Implications for the future
Will Burlingham,Will Chapman
doi : 10.1111/ajt.16524
Volume 21, Issue 7 p. 2319-2320
Circulating host dendrictic cells (DCs) acquire donor MHC antigens either immediately after liver transplantation (Mastoridis et al., page 2387) or after host pretreatment with 'immature' donor-derived DCs (Macedo et al., page 2372), resulting in a unique tolerogenic signal, although, in the latter, host DCs acquire both donor MHC and PD-L1, triggering downregulation of host alloreactive T cells.
Banff and ABMR: Are we going in the right direction?
Michael Mengel,Roslyn B. Mannon
doi : 10.1111/ajt.16546
Volume 21, Issue 7 p. 2321-2322
With the Banff criteria for allograft pathology in kidney transplants scrutinized in this issue by Callemeyn and colleagues (page 2413), Mengel and Mannon comment on their diagnostic versus prognostic ability, recognizing that the diagnostic gold standard of biopsy continues to evolve.
Simultaneous heart-kidney transplant: Working together to define when one organ is not enough
Maryl R. Johnson,Mitra K. Nadim
doi : 10.1111/ajt.16564
Volume 21, Issue 7 p. 2323-2324
A nephrologist and a transplant cardiologist reflect on the recent guidelines for combined heart-kidney transplant. See Kobashigawa et al.'s article on page 2459.
OPO performance improvement and increasing organ transplantation: Metrics are necessary but not sufficient
Kevin O’Connor,Alexandra Glazier
doi : 10.1111/ajt.16545
Volume 21, Issue 7 p. 2325-2326
O'Connor and Glazier comment on evidence-based, targeted initiatives to increase deceased organ donation and the complementary need for improved organ offer acceptance practices by transplant programs to fully realize benefits for patients awaiting transplantation. See the article from Doby et al. on page 2555.
Dismantling structural racism as a root cause of racial disparities in COVID-19 and transplantation
Tanjala S. Purnell,Dinee C. Simpson,Clive O. Callender,L. Ebony Boulware
doi : 10.1111/ajt.16543
Volume 21, Issue 7 p. 2327-2332
As the United States faces unparalleled challenges due to COVID-19, racial disparities in health and healthcare have once again taken center stage. If effective interventions to address racial disparities in transplantation, including those magnified by COVID-19, are to be designed and implemented at the national level, it is first critical to understand the complex mechanisms by which structural, institutional, interpersonal, and internalized racism influence the presence of racial disparities in healthcare and transplantation. Specifically, we must deeply re-evaluate how scientists and clinicians think about race in the transplant context, and we must actively shift our efforts from merely observing disparities to acknowledging and acting on racism as a root cause underlying the vast majority of these disparities. We must do better to ensure equitable access and outcomes for all transplant patients, including within the current COVID-19 pandemic. We respectfully offer this viewpoint as a call to action to every reader to join us in working together to help dismantle racist influences and advance transplant equity.
The respiratory microbiome after lung transplantation: Reflection or driver of respiratory disease?
Caroline C. Eskind,Meghan H. Shilts,Ciara M. Shaver,Suman R. Das,Gowri Satyanarayana
doi : 10.1111/ajt.16568
Volume 21, Issue 7 p. 2333-2340
With the introduction of high-throughput sequencing methods, our understanding of the human lower respiratory tract's inhabitants has expanded significantly in recent years. What is now termed the “lung microbiome” has been described for healthy patients, as well as people with chronic lung diseases and lung transplants. The lung microbiome of lung transplant recipients (LTRs) has proven to be unique compared with nontransplant patients, with characteristic findings associated with disease states, such as pneumonia, acute rejection, and graft failure. In this review, we summarize the current understanding of the lung microbiome in LTRs, not only focusing on bacteria but also highlighting key findings of the viral and the fungal community. Based on our knowledge of the lung microbiome in LTRs, we propose multiple opportunities for clinical use of the microbiome to improve outcomes in this population.
Microbiota and immunoregulation: A focus on regulatory B lymphocytes and transplantation
Margaux Pacaud,Luc Colas,Sophie Brouard
doi : 10.1111/ajt.16522
Volume 21, Issue 7 p. 2341-2347
The microbiota plays a major role in the regulation of the host immune functions thus establishing a symbiotic relationship that maintains immune homeostasis. Among immune cells, regulatory B cells (Bregs), which can inhibit effector T cell responses, may be involved in the intestinal homeostasis. Recent works suggest that the interaction between the microbiota and Bregs appears to be important to limit autoimmune diseases and help to maintain tolerance in transplantation. Short-chain fatty acids (SCFAs), recognized as major metabolites of the microbiota, seem to be involved in the generation of a pro-tolerogenic environment in the gut, particularly through the regulation of B cell differentiation, limiting mature B cells and promoting the function of Bregs. In this review, we show that this B cells–microbiota interaction may open a path toward new potential therapeutic applications not only for patients with autoimmune diseases but also in transplantation.
Mesenchymal stromal cell treatment of donor kidneys during ex vivo normothermic machine perfusion: A porcine renal autotransplantation study
Stine Lohmann,Merel B. F. Pool,Kaithlyn M. Rozenberg,Anna K. Keller,Cyril Moers,Ulla M?ldrup,Bjarne K. M?ller,Stina J. M. Lignell,S?ren Krag,Jesus M. Sierra-Parraga,Maria L. Lo Faro,James Hunter,Martin J. Hoogduijn,Carla C. Baan,Henri G. D. Leuvenink,Rutger J. Ploeg,Marco Eijken,Bente Jespersen
doi : 10.1111/ajt.16473
Volume 21, Issue 7 p. 2348-2359
Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti-inflammatory effects in ischemia-reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC treatment of kidneys during NMP using a porcine autotransplantation model, and examine potential MSC treatment-associated kidney improvements up to 14 days posttransplant. After 75 min of kidney warm ischemia, four experimental groups of n = 7 underwent 14 h of oxygenated hypothermic machine perfusion. In three groups this was followed by 240 min of NMP with infusion of vehicle, 10 million porcine, or 10 million human adipose-derived MSCs. All kidneys were autotransplanted after contralateral nephrectomy. MSC treatment did not affect perfusion hemodynamics during NMP or cause adverse effects at reperfusion, with 100% animal survival. MSCs did not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase-associated lipocalin concentrations or kidney damage assessed by histology during the 14 days, and MSCs retention was demonstrated in renal cortex. Infusing MSCs during ex vivo NMP of porcine kidneys was safe and feasible. Within the short posttransplant follow-up period, no beneficial effects of ex vivo MSC therapy could be demonstrated.
Interleukin 6 trans-signaling is a critical driver of lung allograft fibrosis
David S. Wheeler,Keizo Misumi,Natalie M. Walker,Ragini Vittal,Michael P. Combs,Yoshiro Aoki,Russell R. Braeuer,Vibha N. Lama
doi : 10.1111/ajt.16417
Volume 21, Issue 7 p. 2360-2371
Histopathologic examination of lungs afflicted by chronic lung allograft dysfunction (CLAD) consistently shows both mononuclear cell (MNC) inflammation and mesenchymal cell (MC) fibroproliferation. We hypothesize that interleukin 6 (IL-6) trans-signaling may be a critical mediator of MNC-MC crosstalk and necessary for the pathogenesis of CLAD. Bronchoalveolar lavage (BAL) fluid obtained after the diagnosis of CLAD has approximately twofold higher IL-6 and soluble IL-6 receptor (sIL-6R) levels compared to matched pre-CLAD samples. Human BAL-derived MCs do not respond to treatment with IL-6 alone but have rapid and prolonged JAK2-mediated STAT3 Tyr705 phosphorylation when exposed to the combination of IL-6 and sIL-6R. STAT3 phosphorylation within MCs upregulates numerous genes causing increased invasion and fibrotic differentiation. MNC, a key source of both IL-6 and sIL-6R, produce minimal amounts of these proteins at baseline but significantly upregulate production when cocultured with MCs. Finally, the use of an IL-6 deficient recipient in a murine orthotopic transplant model of CLAD reduces allograft fibrosis by over 50%. Taken together these results support a mechanism where infiltrating MNCs are stimulated by resident MCs to release large quantities of IL-6 and sIL-6R which then feedback onto the MCs to increase invasion and fibrotic differentiation.
Donor-derived regulatory dendritic cell infusion results in host cell cross-dressing and T cell subset changes in prospective living donor liver transplant recipients
Camila Macedo,Lillian M. Tran,Alan F. Zahorchak,Helong Dai,Xinyan Gu,Ranjithkumar Ravichandran,Thalachallour Mohanakumar,Beth Elinoff,Adriana Zeevi,Mindi A. Styn,Abhinav Humar,Fadi G. Lakkis,Diana M. Metes,Angus W. Thomson
doi : 10.1111/ajt.16393
Volume 21, Issue 7 p. 2372-2386
Regulatory dendritic cells (DCreg) promote transplant tolerance following their adoptive transfer in experimental animals. We investigated the feasibility, safety, fate, and impact on host T cells of donor monocyte-derived DCreg infused into prospective, living donor liver transplant patients, 7 days before transplantation. The DCreg expressed a tolerogenic gene transcriptional profile, high cell surface programed death ligand-1 (PD-L1):CD86 ratios, high IL-10/no IL-12 productivity and poor ability to stimulate allogeneic T cell proliferation. Target DCreg doses (range 2.5–10 ?— 106 cells/kg) were achieved in all but 1 of 15 recipients, with no infusion reactions. Following DCreg infusion, transiently elevated levels of donor HLA and immunoregulatory PD-L1, CD39, and CD73 were detected in circulating small extracellular vesicles. At the same time, flow and advanced image stream analysis revealed intact DCreg and “cross-dressingâ€� of host DCs in blood and lymph nodes. PD-L1 co-localization with donor HLA was observed at higher levels than with recipient HLA. Between DCreg infusion and transplantation, T-bethiEomeshi memory CD8+ T cells decreased, whereas regulatory (CD25hiCD127−Foxp3+): T-bethiEomeshi CD8+ T cell ratios increased. Thus, donor-derived DCreg infusion may induce systemic changes in host antigen-presenting cells and T cells potentially conducive to modulated anti-donor immune reactivity at the time of transplant.
Impact of donor extracellular vesicle release on recipient cell “cross-dressing� following clinical liver and kidney transplantation
Sotiris Mastoridis,Mar?a-Carlota Londo?±o,Ada Kurt,Elisavet Kodela,Elena Crespo,John Mason,Oriol Bestard,Marc Mart?nez-Llordella,Alberto S??nchez-Fueyo
doi : 10.1111/ajt.16123
Volume 21, Issue 7 p. 2387-2398
In several murine models of transplantation, the “cross-dressing� of recipient antigen presenting cells (APCs) with intact donor major histocompatibility complex (MHC) derived from allograft-released small extracellular vesicles (sEVs) has been recently described as a key mechanism in eliciting and sustaining alloimmune responses. Investigation of these processes in clinical organ transplantation has, however, been hampered by the lack of sensitivity of conventional instruments and assays. We have employed advanced imaging flow cytometry (iFCM) to explore the kinetics of allograft sEV release and the extent to which donor sEVs might induce cross-dressing following liver and kidney transplantation. We report for the first time that recipient APC cross-dressing can be transiently detected in the circulation shortly after liver, but not kidney, transplantation in association with the release of HLA-bearing allograft-derived sEVs. In liver transplant recipients the majority of circulating cells exhibiting donor HLA are indeed cross-dressed cells and not passenger leukocytes. In keeping with experimental animal data, the downstream functional consequences of the transfer of circulating sEVs harvested from human transplant recipients varies depending on the type of transplant and time posttransplant. sEVs released shortly after liver, but not kidney, transplantation exhibit immunoinhibitory effects that could influence liver allograft immunogenicity.
Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation
Arianna Barbetta,Mayada Aljehani,Michelle Kim,Christine Tien,Aaron Ahearn,Hannah Schilperoort,Linda Sher,Juliet Emamaullee
doi : 10.1111/ajt.16440
Volume 21, Issue 7 p. 2399-2412
Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81–0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R2 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.
Revisiting the changes in the Banff classification for antibody-mediated rejection after kidney transplantation
Jasper Callemeyn,Heleen Ameye,Evelyne Lerut,Aleksandar Senev,Maarten Coemans,Elisabet Van Loon,Ben Sprangers,Vicky Van Sandt,Maud Rabeyrin,Val?©rie Dubois,Olivier Thaunat,Dirk Kuypers,Marie-Paule Emonds,Maarten Naesens
doi : 10.1111/ajt.16474
Volume 21, Issue 7 p. 2413-2423
The Banff classification for antibody-mediated rejection (ABMR) has undergone important changes, mainly by inclusion of C4d-negative ABMR in Banff’13 and elimination of suspicious ABMR (sABMR) with the use of C4d as surrogate for HLA-DSA in Banff’17. We aimed to evaluate the numerical and prognostic repercussions of these changes in a single-center cohort study of 949 single kidney transplantations, comprising 3662 biopsies that were classified according to the different versions of the Banff classification. Overall, the number of ABMR and sABMR cases increased from Banff’01 to Banff’13. In Banff’17, 248 of 292 sABMR biopsies were reclassified to No ABMR, and 44 of 292 to ABMR. However, reclassified sABMR biopsies had worse and better outcome than No ABMR and ABMR, which was mainly driven by the presence of microvascular inflammation and absence of HLA-DSA, respectively. Consequently, the discriminative performance for allograft failure was lowest in Banff’17, and highest in Banff’13. Our data suggest that the clinical and histological heterogeneity of ABMR is inadequately represented in a binary classification system. This study provides a framework to evaluate the updates of the Banff classification and assess the impact of proposed changes on the number of cases and risk stratification. Two alternative classifications introducing an intermediate category are explored.
Optimal donation of kidney transplants after controlled circulatory death
Emilie Savoye,Camille Legeai,Julien Branchereau,Samuel Gay,Bruno Riou,Francois Gaudez,Benoit Veber,Franck Bruyere,Gaelle Cheisson,Thomas Kerforne,Lionel Badet,Olivier Bastien,Corinne Antoine,and the cDCD National Steering Committee
doi : 10.1111/ajt.16425
Volume 21, Issue 7 p. 2424-2436
Controlled donation after circulatory death (cDCD) is used for “extended criteria” donors with poorer kidney transplant outcomes. The French cDCD program started in 2015 and is characterized by normothermic regional perfusion, hypothermic machine perfusion, and short cold ischemia time. We compared the outcomes of kidney transplantation from cDCD and brain-dead (DBD) donors, matching cDCD and DBD kidney transplants by propensity scoring for donor and recipient characteristics. The matching process retained 442 of 499 cDCD and 809 of 6185 DBD transplantations. The DGF rate was 20% in cDCD recipients compared with 28% in DBD recipients (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI] 1.12–1.82). When DBD transplants were ranked by cold ischemia time and machine perfusion use and compared with cDCD transplants, the aRR of DGF was higher for DBD transplants without machine perfusion, regardless of the cold ischemia time (aRR with cold ischemia time <18 h, 1.57; 95% CI 1.20–2.03, vs aRR with cold ischemia time ?18 h, 1.79; 95% CI 1.31–2.44). The 1-year graft survival rate was similar in both groups. Early outcome was better for kidney transplants from cDCD than from matched DBD transplants with this French protocol.
Association of time-updated plasma calcium and phosphate with graft and patient outcomes after kidney transplantation
Willemijn Y. van der Plas,Ant?³nio W. Gomes Neto,Stefan P. Berger,Robert A. Pol,Schelto Kruijff,Stephan J. L. Bakker,Martin H. de Borst
doi : 10.1111/ajt.16457
Volume 21, Issue 7 p. 2437-2447
Disturbances in calcium-phosphate homeostasis are common after kidney transplantation. We aimed to assess the relationship between deregulations in plasma calcium and phosphate over time and mortality and death-censored graft failure (DCGF). In this prospective cohort study, we included kidney transplant recipients with ≥2 plasma calcium and phosphate measurements. Data were analyzed using time-updated Cox regression analyses adjusted for potential confounders including time-updated kidney function. We included 2769 patients (mean age 47 ?± 14 years, 42.3% female) with 138 496 plasma calcium and phosphate levels (median [IQR] 43 [31–61] measurements per patient). During follow-up of 16.3 [8.7–25.2] years, 17.2% developed DCGF and 7.9% died. Posttransplant hypercalcemia was associated with an increased risk of mortality (1.63 [1.31–2.00], p < 0.0001), but not with DCGF. Hyperphosphatemia was associated with both DCGF (2.59 [2.05–3.27], p < .0001) and mortality (3.14 [2.58–3.82], p < .0001). Only the association between hypercalcemia and mortality remained significant in sensitivity analyses censored by a simultaneous eGFR <45 mL/min/1.73 m2. Hypocalcemia and hypophosphatemia were not consistently associated with either outcome. Posttransplant hypercalcemia, even in the presence of preserved kidney function, was associated with an increased mortality risk. Associations of hyperphosphatemia with DCGF and mortality may be driven by eGFR.
Increased incidence and unusual presentations of CMV disease in kidney transplant recipients after conversion to belatacept
Nathalie Chavarot,Gillian Divard,Anne Scemla,Lucile Amrouche,Olivier Aubert,Marianne Leruez-Ville,Marc O. Timsit,Claire Tinel,Julien Zuber,Christophe Legendre,Dany Anglicheau,Rebecca Sberro-Soussan
doi : 10.1111/ajt.16430
Volume 21, Issue 7 p. 2448-2458
Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4–68.5]) were converted to belatacept (median of 11.5 months [2.5–37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R? CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.
Consensus conference on heart-kidney transplantation
Jon Kobashigawa,Darshana M. Dadhania,Maryjane Farr,W. H. Wilson Tang,Arvind Bhimaraj,Lawrence Czer,Shelley Hall,Abdolreza Haririan,Richard N. Formica,Jignesh Patel,Rafael Skorka,Savitri Fedson,Titte Srinivas,Jeffrey Testani,Julie M. Yabu,Xingxing S. Cheng, on behalf of the Consensus Conference Participants
doi : 10.1111/ajt.16512
Volume 21, Issue 7 p. 2459-2467
Simultaneous heart-kidney transplant (sHK) has enabled the successful transplantation of patients with end-stage heart disease and concomitant kidney disease, with non-inferior outcomes to heart transplant (HT) alone. The decision for sHK is challenged by difficulties in differentiating those patients with a significant component of reversible kidney injury due to cardiorenal syndrome who may recover kidney function after HT, from those with intrinsic advanced kidney disease who would benefit most from sHK. A consensus conference on sHK took place on June 1, 2019 in Boston, Massachusetts. The conference represented a collaborative effort by experts in cardiothoracic and kidney transplantation from centers across the United States to explore the development of guidelines for the interdisciplinary criteria for kidney transplantation in the sHK candidate, to evaluate the current allocation of kidneys to follow the heart for sHK, and to recommend standardized care for the management of sHK recipients. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical problems related to multi-organ transplantation were also debated. The findings and consensus statements are presented.
Need for improvements in simultaneous heart-kidney allocation: The limitation of pretransplant glomerular filtration rate
Brian I. Shaw,Mariya L. Samoylova,Scott Sanoff,Andrew S. Barbas,Debra L. Sudan,L. Ebony Boulware,Lisa M. McElroy
doi : 10.1111/ajt.16466
Volume 21, Issue 7 p. 2468-2478
The incidence of simultaneous heart-kidney transplant (SHK) has increased markedly in the last 15 years. There are no universally agreed upon indications for SHK vs. heart alone (HA) transplant, and center evaluation processes vary widely. We utilized Scientific Registry of Transplant Recipients data from 2003 to 2017 to quantify changes in the practice of SHK, examine the survival of SHK vs. HA, and identify patients with marginal benefit from SHK. We used Kaplan–Meier curves and Cox proportional hazards to assess differences in survival. The incidence of SHK increased more than fourfold between 2003 and 2017 from 1.6% to 6.6% of total hearts transplanted, while the proportion of dialysis-dependent patients undergoing SHK has remained constant. SHK was associated with increased survival in dialysis-dependent patients (Median Survival SHK: 12.6 vs. HA: 7.1 years p < .0001) but not with nondialysis-dependent patients (Median Survival SHK: 12.5 vs. HA 12.3, p = .24). The marginal effect of SHK in decreasing the hazard of death diminished with increasing eGFR. Delayed graft function occurred in 26% of SHK recipients. Posttransplant chronic dialysis was similar for both operations (6.4% of HA and 6.0% of SHK). Further study is needed to define patients who benefit from SHK.
Complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients
Jignesh K. Patel,Guillaume Coutance,Alexandre Loupy,Deanna Dilibero,Michele Hamilton,Michelle Kittleson,Evan Kransdorf,Babak Azarbal,Osamu Seguchi,Xiaohai Zhang,David Chang,Dael Geft,Lawrence Czer,Shaida Varnous,Jon A. Kobashigawa
doi : 10.1111/ajt.16420
Volume 21, Issue 7 p. 2479-2488
Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre–formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%–97%) and 6250 (5000–10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14–0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk.
Early ?²-lactam concentrations and infectious complications after lung transplantation
Fabio S. Taccone,Elisa G. Bogossian,Rafael M. Tironi,Elio Antonucci,Maya Hites,Christiane Knoop,Isabelle Etienne,Fr?©d?©rique Jacobs,Jacques Creteur
doi : 10.1111/ajt.16432
Volume 21, Issue 7 p. 2489-2497
Antibiotic underdosing in prophylactic antibiotic regimes after lung transplantation (LTx) can increase the risk of infection. We aimed to study whether ?²-lactam concentrations achieved desirable pharmacodynamic targets in the early phase after LTx and the association between drug concentrations and the development of early infections or the acquisition of multidrug-resistant (MDR) strains. We reviewed patients in whom broad-spectrum ?²-lactam levels were measured after LTx during antibiotic prophylaxis. ?²-Lactam concentrations were considered “insufficientâ€� if drug levels remained below four times the clinical breakpoint of the minimal inhibitory concentration for Pseudomonas aeruginosa. The primary outcome was the occurrence of an infection and/or acquisition of MDR pathogens in the first 14 days after transplantation. A total of 70 patients were included. “Insufficientâ€� drug concentrations were found in 40% of patients. In 27% of patients, an early MDR pathogen was identified and 49% patients were diagnosed with an early posttransplant infection. Patients with “insufficientâ€� drug concentrations acquired more frequently MDR bacteria and/or developed an infection than others (22/28, 79% vs. 20/42, 48% – p = .01). ?²-Lactam levels were often found to be below the desired drug targets in the early phase after transplantation and may be associated with the occurrence of early infectious complications.
Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: A retrospective cohort
Robin K. Avery,Teresa Po-Yu Chiang,Kieren A. Marr,Daniel C. Brennan,Afrah S. Sait,Brian T. Garibaldi,Pali Shah,Darin Ostrander,Seema Mehta Steinke,Nitipong Permpalung,Willa Cochran,Martin A. Makary,Jacqueline Garonzik-Wang,Dorry L. Segev,Allan B. Massie
doi : 10.1111/ajt.16431
Volume 21, Issue 7 p. 2498-2508
Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p < .001), hypertension (69% vs. 44%, p = .001), HIV (7% vs. 1.4%, p = .024), and peripheral vascular disorders (19% vs. 8%, p = .018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p = .13), length-of-stay (sHR: 0.91.11.4, p = .5), or mortality (sHR: 0.10.41.6, p = .19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non-SOT (median [IQR] 4 [3–4]) (p = .042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.760.810.86, p < .001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.
Incidence and outcome of SARS-CoV-2 infection on solid organ transplantation recipients: A nationwide population-based study
Silvia Trapani,Lucia Masiero,Francesca Puoti,Maria C. Rota,Martina Del Manso,Letizia Lombardini,Flavia Riccardo,Antonio Amoroso,Patrizio Pezzotti,Paolo A. Grossi,Silvio Brusaferro,Massimo Cardillo,the Italian Network of Regional Transplant Coordinating Centers Collaborating group,Italian Surveillance System of Covid-19, Italian Society for Organ Transplantation (SITO), The Italian Board of Experts in Liver Transplantation (I-BELT) Study Group, Italian Association for the Study of the Liver (AISF), Italian Society of Nephrology (SIN), SIN-SITO Study Group
doi : 10.1111/ajt.16428
Volume 21, Issue 7 p. 2509-2521
Since February 21 2020, when the Italian National Institute of Health (Istituto Superiore di Sanit? –ISS) reported the first autochthonous case of infection, a dedicated surveillance system for SARS-CoV-2-positive (COVID+) cases has been created in Italy. These data were cross-referenced with those inside the Information Transplant System in order to assess the cumulative incidence (CI) and the outcome of SARS-COV-2 infection in solid organ transplant recipients (SOTRs) who are assumed to be most at risk. We compared our results with those of COVID+ nontransplanted patients (Non-SOTRs) with follow-up through September 30, 2020. The CI of SARS-CoV-2 infection in SOTRs was 1.02%, higher than in COVID+ Non-SOTRs (0.4%, p < .05) with a greater risk in the Lombardy region (2.89%). The CI by type of organ transplant was higher for heart (CI 1.57%, incidence rate ratio [IRR] 1.36) and lower for liver (CI 0.63%, IRR 0.54). The 60-day CI of mortality was 30.6%, twice as much that of COVID+ Non-SOTRs (15.4%) with a 60-day gender and age adjusted odds ratio (adjusted-OR) of 3.83 for COVID+ SOTRs (95% confidence interval [3.03–4.85]). The lowest 60-day adjusted-OR was observed in liver SOTRs (OR 0.46, 95% confidence interval [0.25–0.86]). More detailed studies on disease management and evolution will be necessary in these patients at greater risk of COVID-19.
An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients
Vinay Nair,Nicholas Jandovitz,Jamie S. Hirsch,Mersema Abate,Sanjaya K. Satapathy,Nitzan Roth,Santiago J. Miyara,Sara Guevara,Adam M. Kressel,Alec Xiang,Grace Wu,Samuel D. Butensky,David Lin,Stephanie Williams,Madhu C. Bhaskaran,David T. Majure,Elliot Grodstein,Lawrence Lau,Gayatri Nair,Ahmed E. Fahmy,Aaron Winnick,Nadine Breslin,Ilan Berlinrut,Christine Molmenti,Lance B. Becker,Prashant Malhotra,Pranisha Gautam-Goyal,Brian Lima,Simon Maybaum,Samit K. Shah,Ryosuke Takegawa,Kei Hayashida,Koichiro Shinozaki,Lewis W. Teperman,Ernesto P. Molmenti,Northwell Health COVID-19 Research Consortium
doi : 10.1111/ajt.16460
Volume 21, Issue 7 p. 2522-2531
We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant na?¯ve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99–1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03–1.74, p = .027).
Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study
Laura N. Walti,Catrina Mugglin,Daniel Sidler,Matteo Mombelli,Oriol Manuel,Hans H. Hirsch,Nina Khanna,Nicolas Mueller,Christoph Berger,Katia Boggian,Christian Garzoni,Dionysios Neofytos,Christian van Delden,Cédric Hirzel,Swiss Transplant Cohort Study (STCS)
doi : 10.1111/ajt.16423
Volume 21, Issue 7 p. 2532-2542
Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein–Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV? PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199–1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751–6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077–0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.
Interleukin-6 blockade with tocilizumab increases Tregs and reduces T effector cytokines in renal graft inflammation: A randomized controlled trial
Sindhu Chandran,Joey Leung,Crystal Hu,Zoltan G. Laszik,Qizhi Tang,Flavio G. Vincenti
doi : 10.1111/ajt.16459
Volume 21, Issue 7 p. 2543-2554
Interleukin-6 (IL-6) is a proinflammatory cytokine and key regulator of Treg: T effector cell (Teff) balance. We hypothesized that IL-6 blockade with tocilizumab, a monoclonal antibody to IL-6R, would increase Tregs, dampen Teff function, and control graft inflammation. We conducted a randomized controlled clinical trial (2014–2018) of clinically stable kidney transplant recipients on calcineurin inhibitor, mycophenolate mofetil, and prednisone, with subclinical graft inflammation noted on surveillance biopsies during the first year posttransplant. Subjects received tocilizumab (8 mg/kg IV every 4 weeks; 6 doses; n = 16) or no treatment (controls; n = 14) on top of usual maintenance immunosuppression. Kidney biopsies pre- and post-treatment were analyzed using Banff criteria. Blood was analyzed for serum cytokines, Treg frequencies, and T cell effector molecule expression (IFN-?³, IL-17, granzyme B) post-stimulation ex vivo. Tocilizumab-treated subjects were more likely to show improved Banff ti-score (62.5% vs. 21.4%, p = .03), increased Treg frequency (7.1% ?± 5.55% vs. 3.6% ?± 1.7%, p = .0168), and a blunted Teff cytokine response compared to controls. Changes in Banff i- and t-scores were not significantly different. The treatment was relatively well tolerated with no patient deaths or graft loss. Blockade of IL-6 is a novel and promising treatment option to regulate the T cell alloimmune response in kidney transplant recipients. NCT02108600.
Results of a data-driven performance improvement initiative in organ donation
Brianna L. Doby,Kellie Hanner,Steven Johnson,Tanjala S. Purnell,Malay B. Shah,Raymond J. Lynch
doi : 10.1111/ajt.16442
Volume 21, Issue 7 p. 2555-2562
New metrics for organ procurement organization (OPO) performance utilize National Center for Health Statistics data to measure cause, age, and location consistent (CALC) deaths. We used this denominator to identify opportunities for improved donor conversion at one OPO, Indiana Donor Network (INOP). We sought to determine whether such analyses are immediately actionable for quality improvement (QI) initiatives directed at increased donor conversion. CALC-based assessment of INOP’s performance revealed an opportunity to improve conversion of older donors. Following the QI initiative, INOP donor yield rose by 44%, while organs transplanted rose by 29%. These changes tolerated temporary disruption around the COVID-19 pandemic. Improved donor yield was primarily seen in older groups identified by CALC-based methods. Process changes in resource allocation and monitoring were associated with a 57% increase in the number of potential donors approached in the QI period and a subsequent rise in the number of potential donor referrals, suggesting positive feedback at area hospitals. Post-intervention, INOP’s projected donation performance rose from 51st to 18th among all OPOs. OPOs can use CALC death data to accurately assess donor conversion by categories including age and race/ethnicity. These data can be used in real time to inform OPO-level processes to maximize donor recovery.
COVID-19 mortality among kidney transplant candidates is strongly associated with social determinants of health
Jesse D. Schold,Kristen L. King,S. Ali Husain,Emilio D. Poggio,Laura D. Buccini,Sumit Mohan
doi : 10.1111/ajt.16578
Volume 21, Issue 7 p. 2563-2572
The COVID-19 pandemic has affected all portions of the global population. However, many factors have been shown to be particularly associated with COVID-19 mortality including demographic characteristics, behavior, comorbidities, and social conditions. Kidney transplant candidates may be particularly vulnerable to COVID-19 as many are dialysis-dependent and have comorbid conditions. We examined factors associated with COVID-19 mortality among kidney transplant candidates from the National Scientific Registry of Transplant Recipients from March 1 to December 1, 2020. We evaluated crude rates and multivariable incident rate ratios (IRR) of COVID-19 mortality. There were 131 659 candidates during the study period with 3534 all-cause deaths and 384 denoted a COVID-19 cause (5.00/1000 person years). Factors associated with increased COVID-19 mortality included increased age, males, higher body mass index, and diabetes. In addition, Blacks (IRR = 1.96, 95% C.I.: 1.43–2.69) and Hispanics (IRR = 3.38, 95% C.I.: 2.46–4.66) had higher COVID-19 mortality relative to Whites. Patients with lower educational attainment, high school or less (IRR = 1.93, 95% C.I.: 1.19–3.12, relative to post-graduate), Medicaid insurance (IRR = 1.73, 95% C.I.: 1.26–2.39, relative to private), residence in most distressed neighborhoods (fifth quintile IRR = 1.93, 95% C.I.: 1.28–2.90, relative to first quintile), and most urban and most rural had higher adjusted rates of COVID-19 mortality. Among kidney transplant candidates in the United States, social determinants of health in addition to demographic and clinical factors are significantly associated with COVID-19 mortality.
Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry
Florentino Villanego,Auxiliadora Mazuecos,Isabel M. P?©rez-Flores,Francesc Moreso,Amado Andr?©s,Carlos Jim?©nez-Mart?n,Mar?a Molina,Cristina Canal,Luis A. S??nchez-C??mara,Sof?a Z??rraga,Mar?a del Carmen Ruiz-Fuentes,Mar?a Jos?© Aladr?©n,Edoardo Melilli,Ver?³nica L?³pez,Emilio S??nchez-?�lvarez,Marta Crespo,Julio Pascual,for the Spanish Society of Nephrology COVID-19 Group
doi : 10.1111/ajt.16579
Volume 21, Issue 7 p. 2573-2582
SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July–December) than in the first one (March–June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.
T cell antigenicity and immunogenicity of allogeneic exosomes
Aurore Prunevieille,Mohamed H. Babiker-Mohamed,Colleen Aslami,Bruno Gonzalez-Nolasco,Nuala Mooney,Gilles Benichou
doi : 10.1111/ajt.16591
Volume 21, Issue 7 p. 2583-2589
Extracellular vesicles, including exosomes, are regularly released by allogeneic cells after transplantation. Recipient antigen-presenting cells (APCs) capture these vesicles and subsequently display donor MHC molecules on their surface. Recent evidence suggests that activation of alloreactive T cells by the so-called cross-dressed APCs plays an important role in initiating the alloresponse associated with allograft rejection. On the other hand, whether allogeneic exosomes can bind to T cells on their own and activate them remains unclear. In this study, we showed that allogeneic exosomes can bind to T cells but do not stimulate them in vitro unless they are cultured with APCs. On the other hand, allogeneic exosomes activate T cells in vivo and sensitize mice to alloantigens but only when delivered in an inflammatory environment.
Post-mortem molecular investigations of SARS-CoV-2 in an unexpected death of a recent kidney transplant recipient
Emily Lauren Simms,Hyunjae Chung,Lisa Oberding,Daniel A. Muruve,Braedon McDonald,Amy Bromley,Dylan R. Pillai,Justin Chun
doi : 10.1111/ajt.16549
Volume 21, Issue 7 p. 2590-2595
Solid organ transplant recipients are vulnerable to severe infection during induction therapy. We report a case of a 67-year-old male who died unexpectedly 10 days after receiving a kidney transplant on February 10, 2020. There was no clear cause of death, but COVID-19 was considered retrospectively, as the death occurred shortly after the first confirmed case of COVID-19 in Canada. We confirmed the presence of SARS-CoV-2 components in the renal allograft and native lung tissue using immunohistochemistry for SARS-CoV-2 spike protein and RNA scope in situ hybridization for SARS-CoV-2 RNA. Results were reaffirmed with the Food and Drug Administration Emergency Use Authorization approved Bio-Rad SARS-CoV-2 digital droplet PCR for the kidney specimen. Our case highlights the importance of patient autopsies in an unfolding global pandemic and demonstrates the utility of molecular assays to diagnose SARS-CoV-2 post-mortem. SARS-CoV-2 infection during induction therapy may portend a fatal clinical outcome. We also suggest COVID-19 may be transmittable via renal transplant.
Multisystem inflammatory syndrome in children associated with SARS-CoV-2 in a solid organ transplant recipient
Leanne M. Petters,Tiphanie P. Vogel,Flor M. Munoz,Jose A. Hernandez,Sarah Koohmaraie,Michael J. Nowicki,Caleb E. Zumbro,Krupa R. Mysore
doi : 10.1111/ajt.16572
Volume 21, Issue 7 p. 2596-2599
We present the case of a 3-year-old female liver transplant recipient with a history of Caroli disease who presented with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) test and was ultimately diagnosed with multisystem inflammatory syndrome in children (MIS-C) complicated by portal vein thrombosis. To the best of our knowledge, this is the first case report of MIS-C in a pediatric solid organ transplant (SOT) recipient. Based on our patient, MIS-C could be a potential complication of Coronavirus disease 2019 (COVID-19) in SOT recipients and may have a negative outcome on transplant graft function.
Liver transplantation performed in a SARS-CoV-2 positive hospitalized recipient using a SARS-CoV-2 infected donor
Tommaso Maria Manzia,Carlo Gazia,Ilaria Lenci,Roberta Angelico,Luca Toti,Andrea Monaco,Alessandro Anselmo,Leonardo Baiocchi,Paolo Grossi,Giuseppe Tisone
doi : 10.1111/ajt.16548
Volume 21, Issue 7 p. 2600-2604
The coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 currently affected more than 108 million people worldwide with a fatality rate of 2.2%. Herein, we report the first case of liver transplantation (LT) performed with a liver procured from a SARS-CoV-2 positive donor. The recipient was a 35-year-old SARS-CoV-2 positive female patient affected by severe end-stage HBV-HDV-related liver disease (model of end-stage liver disease = 32) who had neutralizing SARS-CoV-2 antibodies (titers 1:320) at time of LT. The LT was successful, and the graft is functioning two months after surgery. The recipient cleared the SARS-CoV-2 infection 1 month after LT. The current case shows that the prompt use of SARS-CoV-2 infected liver donors offers an invaluable life-saving opportunity for SARS-CoV-2 positive wait-listed patients who developed neutralizing SARS-CoV-2 antibodies.
Outbreaks associated with treated recreational water — United States, 2015–2019
Michele C. Hlavsa,Samaria K. Aluko,Allison D. Miller,John Person,Megan E. Gerdes,Sooji Lee,Joseph P. Laco,Elizabeth J. Hannapel,Vincent R. Hill
doi : 10.1111/ajt.16037
Volume 21, Issue 7 p. 2605-2609
This article describes 208 outbreaks associated with recreational water exposures in the U.S., the majority of which were due to either Cryptosporidium or Legionella infections and were primarily reported after exposure to public (i.e., nonbackyard) recreational water. These outbreaks resulted in 3646 cases of illness, 286 hospitalizations, and 13 deaths; all deaths were due to Legionella infection. Most outbreaks began between June and August each year, suggesting that solid organ transplant candidates and recipients should be mindful of the risks associated with public recreational water, particularly during the summer months.
Acute renal dysfunction after simultaneous pancreas–kidney transplantation
Eleftherios Gialamas,Michela Assalino,Dela Golshayan,Thierry Berney
doi : 10.1111/ajt.16518
Volume 21, Issue 7 p. 2610-2613
Incorporating kidney-related multi-organ transplants into the kidney allocation sequence
Xingxing S. Cheng,Peter P. Reese
doi : 10.1111/ajt.16542
Volume 21, Issue 7 p. 2614-2615
Cytokine storm induced by a PD1 inhibitor in a renal transplant patient
Arnaud Del Bello,Alexia G. Zakaroff,Nicolas Meyer,Audrey Delas,Stanislas Faguer,Nassim Kamar,Julie Belliere
doi : 10.1111/ajt.16589
Volume 21, Issue 7 p. 2616-2618
The BETA-2 score web app calculator: https://www.beta2score.com/ for assessment of graft function following islet transplantation
Shareen Forbes
doi : 10.1111/ajt.16551
Volume 21, Issue 7 p. 2619-2619
Regulatory updates are needed to prevent the commercialization of islet transplantation in the United States
Piotr Witkowski,Rolf N. Barth,Anthony Japour,Gail Javitt,Jordan S. Pyda,Piotr J. Bachul,Eryk Nowicki,Camillo Ricordi,the “Islet for US Collaborative”
doi : 10.1111/ajt.16555
Volume 21, Issue 7 p. 2620-2622
A call to routinely test lower respiratory tract samples for SARS-CoV-2 in lung donors
Deepali Kumar,Atul Humar,Shaf Keshavjee,Marcelo Cypel
doi : 10.1111/ajt.16576
Volume 21, Issue 7 p. 2623-2624
