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American Journal of Transplantation: Volume 21, Number 11, November 2021
doi : 10.1111/ajt.16054
Volume 21, Issue 11
Two decades have passed since Patrick Kamath and colleagues transformed liver transplantation by establishing that the model for end-stage liver disease (MELD) score predicted mortality risk over the next 90 days for patients with cirrhosis. This seminal discovery led to profound changes in liver allocation policy, first in the United States and then worldwide. Today, the MELD score, since evolved to include serum sodium level (MELD-sodium [MELD-Na]), remains the accepted currency to access deceased donor livers.
Can Social Media Cultivate Living Organ Donors?
Lara C. Pullen PHD
doi : 10.1111/ajt.16051
Volume 21, Issue 11 p. 3505-3506
This month's installment of “The AJT Report” focuses on the growing reliance on social media to inform, educate, and recruit potential living organ donors. We also report on the U.S. Food and Drug Administration’s recent approval of a widely-utilized immunosuppressant for lung transplant rejection prevention.
A new type of programmed inflammatory cell death: PANoptosis
Xian C. Li MD, PHD
doi : 10.1111/ajt.16052
Volume 21, Issue 11 p. 3507-3507
Macrophages exposed to live pathogens die of PANoptosis, a newly described type of inflammatory cell death that involves the activation of all known death pathways.
Transplant surgery: Do the training wheels ever come off?
John C. Magee,Elizabeth A. Pomfret
doi : 10.1111/ajt.16793
Volume 21, Issue 11 p. 3509-3510
MELD-based allocation at 20: Can we evolve and mature?
Therese Bittermann,Peter L. Abt
doi : 10.1111/ajt.16792
Volume 21, Issue 11 p. 3511-3512
This year marks the 20th anniversary of the Model for End-stage Liver Disease (MELD) allocation system for liver transplantation (LT) in the United States. While liver allocation policies have evolved since the adoption of MELD, there have been few changes to how patients' risk of death or delisting is estimated. Revising the MELD score calculation to ensure that candidates are accurately stratified by urgency, while avoiding disparities in access to LT is of immense interest.
Mission accomplished? Early data from the simultaneous liver-kidney transplantation allocation policy
Sumeet K. Asrani,Josh Levitsky
doi : 10.1111/ajt.16796
Volume 21, Issue 11 p. 3513-3515
Dual organ transplantation offers a unique ethical and resource allocation dilemma, whereby competing interests across the patient, provider, and transplant center spectrum play into the decision-making process. On the one hand, patients with decompensated cirrhosis have a high risk of acute kidney injury (AKI) and have chronic conditions that predispose them to chronic kidney disease (CKD). For these populations, simultaneous liver-kidney transplantation (SLKT) has traditionally had superior survival as compared to liver transplantation alone (LTA), leading to centers to preferentially choose SLKT. On the other hand, kidney transplant alone (KTA) in patients without liver disease also offers a survival advantage as compared to remaining on the waitlist. Because of the increase in the number of SLKT over the last decades and lack of standardized allocation criteria, the OPTN implemented strict AKI and CKD-based criteria for SLKT eligibility in 2017. The policy also included a safety net to offer increased priority for kidney after liver transplantation (KALT) in the presence of severe post-LTA kidney dysfunction. The overall goals of the policy were to blunt the rise of SLKT without affecting post-LT survival and, in doing so, increase organ availability for KTA.
Maximizing the use of hard to place kidneys: Getting the right kidney to the right recipient at the right time
Peter G. Stock,Krista L. Lentine
doi : 10.1111/ajt.16771
Volume 21, Issue 11 p. 3516-3518
Despite the well-known improvements in quantity and quality of life associated with kidney transplantation compared to dialysis, 20% of recovered kidneys are discarded in the United States each year.1At the same time, waiting lists in the United States continue to expand, with waiting times for deceased donor kidney transplants in some geographies exceeding 8 years. The reality is that many waitlisted candidates will no longer be healthy enough for transplantation by the time they matriculate to the top of the bloated waiting lists. Notably, recent evidence suggests that many transplant candidates receive numerous potentially viable deceased donor kidney offers that are refused on their behalf by transplant centers, exacerbating the detrimental consequences of the organ shortage.2The importance of efficiently using every transplantable deceased donor kidney is evident, and is the focus of a new study by Kayler et al. in this issue of AJT.3
C1q as a potential tolerogenic therapeutic in transplantation
William M. Baldwin III,Anna Valujskikh,Robert L. Fairchild
doi : 10.1111/ajt.16705
Volume 21, Issue 11 p. 3519-3523
In 1963, Lepow and colleagues resolved C1, the first component of the classical pathway, into three components, which they named C1q, C1r, and C1s. All three of these components were demonstrated to be involved in causing hemolysis in vitro. For over 30 years after that seminal discovery, the primary function attributed to C1q was as part of the C1 complex that initiated the classical pathway of the complement cascade. Then, a series of papers reported that isolated C1q could bind to apoptotic cells and facilitate their clearance by macrophages. Since then, rheumatologists have recognized that C1q is an important pattern recognition receptor (PRR) that diverts autoantigen containing extracellular vesicles from immune recognition. This critical function of C1q as a regulator of immune recognition has been largely overlooked in transplantation. Now that extracellular vesicles released from transplants have been identified as a major agent of immune recognition, it is logical to consider the potential impact of C1q on modulating the delivery of allogeneic extracellular vesicles to antigen presenting cells. This concept has clinical implications in the possible use of C1q or a derivative as a biological therapeutic to down-modulate immune responses to transplants.
Extended survival versus accelerated rejection of nonhuman primate islet allografts: Effect of mesenchymal stem cell source and timing
Norma S. Kenyon,Melissa A. Willman,Dongmei Han,Rachel S. Leeman,Alex Rabassa,Waldo L. Diaz,James C. Geary,Ena Poumian-Ruiz,Anthony J. Griswold,Derek J. Van Booven,Ryan Thompson,Philip Ordoukhanian,Steven R. Head,Norman M. Kenyon,Kenton G. McHenry,Daniel R. Salomon,Amelia M. Bartholomew,Dora M. Berman
doi : 10.1111/ajt.16693
Volume 21, Issue 11 p. 3524-3537
Mesenchymal stem cells (MSC) have been shown to be immunomodulatory, tissue regenerative, and graft promoting; however, several questions remain with regard to ideal MSC source and timing of administration. In this study, we utilized a rigorous preclinical model of allogeneic islet cell transplantation, incorporating reduced immune suppression and near to complete mismatch of major histocompatibility antigens between the diabetic cynomolgus monkey recipient and the islet donor, to evaluate both the graft promoting impact of MSC source, that is, derived from the islet recipient, the islet donor or an unrelated third party as well as the impact of timing. Co-transplant of MSC and islets on post-operative day 0, followed by additional IV MSC infusions in the first posttransplant month, resulted in prolongation of rejection free and overall islet survival and superior metabolic control for animals treated with recipient as compared to donor or third-party MSC. Immunological analyses demonstrated that infusion of MSC from either source did not prevent alloantibody formation to the islet or MSC donor; however, treatment with recipient MSC resulted in significant downregulation of memory T cells, decreased anti-donor T cell proliferation, and a trend toward increased Tregulatory:Tconventional ratios.
Interleukin-23 receptor signaling by interleukin-39 potentiates T cell pathogenicity in acute graft-versus-host disease
David Bastian,Xiaohui Sui,Hung Dang Nguyen,Yongxia Wu,Steven Schutt,Linlu Tian,Mohammed Hanief Sofi,Yuejun Liu,Paul Martin,Eric Bartee,Xue-Zhong Yu
doi : 10.1111/ajt.16624
Volume 21, Issue 11 p. 3538-3549
IL-12 (p35/p40) and IL-23 (p19/p40) signal through IL-12R (IL-12R?2/?1) and IL-23R (IL-23R?/IL-12R?1), respectively, which can promote pathogenic T lymphocyte activation, differentiation, and function in graft-versus-host disease (GVHD). With the use of murine models of allogeneic hematopoietic cell transplantation (HCT), we found that IL-12R?1 on donor T cells was dispensable to induce acute GVHD development in certain circumstances, while IL-23R? was commonly required. This observation challenges the current paradigm regarding IL-12R?1 as a prerequisite to transmit IL-23 signaling. We hypothesized that p19/EBI3 (IL-39) may have an important role during acute GVHD. With the use of gene transfection and immunoprecipitation approaches, we verified that p19 and EBI3 can form biological heterodimers. We found that IL-39 levels in recipient serum positively correlated with development of acute GVHD in experimental models and in clinical settings, thereby implicating IL-39 in the pathogenesis of acute GVHD. Furthermore, we observed that human T cells can signal in response to IL-39. In chronic GVHD, IL-23R? and IL-12R?1 were similarly required for donor T cell pathogenicity, and IL-39 levels were not significantly different from controls without GVHD. Collectively, we identify a novel cytokine, IL-39, as a pathogenic factor in acute GVHD, which represents a novel potential therapeutic target to control GVHD and other inflammatory disorders.
The natural killer cell activating receptor, NKG2D, is critical to antibody-dependent chronic rejection in heart transplantation
Christine M. Lin,Ronald G. Gill,Borna Mehrad
doi : 10.1111/ajt.16690
Volume 21, Issue 11 p. 3550-3560
Chronic rejection is among the most pressing clinical challenges in solid organ transplantation. Interestingly, in a mouse model of heterotopic heart transplantation, antibody-dependent, natural killer (NK) cell-mediated chronic cardiac allograft vasculopathy occurs in some donor–recipient strain combinations, but not others. In this study, we sought to identify the mechanism underlying this unexplained phenomenon. Cardiac allografts from major histocompatibility complex (MHC) mismatched donors were transplanted into immune-deficient C57Bl/6.rag?/? recipients, followed by administration of a monoclonal antibody against the donor MHC class I antigen. We found marked allograft vasculopathy in hearts from C3H donors, but near-complete protection of BALB/c allografts from injury. We found no difference in recipient NK cell phenotype or intrinsic responsiveness to activating signals between recipients of C3H versus BALB/c allografts. However, cardiac endothelial cells from C3H allografts showed an approximately twofold higher expression of Rae-1, an activating ligand of the NK cell receptor natural killer group 2D (NKG2D). Importantly, the administration of a neutralizing antibody against NKG2D abrogated the development of allograft vasculopathy in recipients of C3H allografts, even in the presence of donor-specific antibodies. Therefore, the activating NK cell receptor NKG2D is necessary in this model of chronic cardiac allograft vasculopathy, and strain-dependent expression of NK activating ligands correlates with the development of this disease.
Long-term control of diabetes in a nonhuman primate by two separate transplantations of porcine adult islets under immunosuppression
Jong-Min Kim,So-Hee Hong,Jun-Seop Shin,Byoung-Hoon Min,Hyun Je Kim,Hyunwoo Chung,Jiyeon Kim,Yoon Ji Bang,Sol Seo,Eung Soo Hwang,Hee-Jung Kang,Jongwon Ha,Chung-Gyu Park
doi : 10.1111/ajt.16704
Volume 21, Issue 11 p. 3561-3572
Porcine islet transplantation is an alternative to allo-islet transplantation. Retransplantation of islets is a routine clinical practice in islet allotransplantation in immunosuppressed recipients and will most likely be required in islet xenotransplantation in immunosuppressed recipients. We examined whether a second infusion of porcine islets could restore normoglycemia and further evaluated the efficacy of a clinically available immunosuppression regimen including anti-thymocyte globulin for induction; belimumab, sirolimus, and tofacitinib for maintenance and adalimumab, anakinra, IVIg, and tocilizumab for inflammation control in a pig to nonhuman primate transplantation setting. Of note, all nonhuman primates were normoglycemic after the retransplantation of porcine islets without induction therapy. Graft survival was >100 days for all 3 recipients, and 1 of the 3 monkeys showed insulin independence for >237 days. Serious lymphodepletion was not observed, and rhesus cytomegalovirus reactivation was controlled without any serious adverse effects throughout the observation period in all recipients. These results support the clinical applicability of additional infusions of porcine islets. The maintenance immunosuppression regimen we used could protect the reinfused islets from acute rejection.
The learning curve of deceased donor liver transplant during fellowship training
Adeel S. Khan,Sandra Garcia-Aroz,Neeta Vachharajani,Heidy Cos,Ola Ahmed,Meranda Scherer,Sarah Matson,Jason M. Wellen,Surendra Shenoy,William C. Chapman,Majella B. Doyle
doi : 10.1111/ajt.16720
Volume 21, Issue 11 p. 3573-3582
Liver transplantation (LT) is a complex operation that most transplant surgeons learn in fellowship. Training varies as there is lack of objective data that can be used to standardize teaching. We performed a retrospective review of our adult LT database with aim of looking at fellow's experience. Using American Society of Transplant Surgery cutoff of, at least 45 LT during fellowship, data for first 45 LT were compared to LT 45–90. Fellow's cases were also clustered in sequential groups of 15 LT and analyzed to estimate the learning curve (LC). Comparison of LT 1–45 with LT 46–90 showed significantly lower total operative times (TOT) (324 vs. 344 min) and warm ischemia times (WIT) (28 vs. 31 min) in the 45–90 group. Rates of biliary complications (23.8% vs. 16.4%) and bile leaks alone (10.3% vs. 5.5%) were significantly higher for first 45 LT. Analysis of fellows experience in sequential clusters of 15 LT showed decreasing TOT, WIT, biliary complications and rates of unplanned return to the OR with progression of fellowship. This study validates the current ASTS requirement of at least 45 LT. LC generated using these data can help individualize training and optimize outcomes through identification of areas in need of improvement.
Joint modeling of liver transplant candidates outperforms the model for end-stage liver disease: The effect of disease development over time on patient outcome
Ben F. J. Goudsmit,Andries E. Braat,Maarten E. Tushuizen,Serge Vogelaar,Jacques Pirenne,Ian P. J. Alwayn,Bart van Hoek,Hein Putter
doi : 10.1111/ajt.16730
Volume 21, Issue 11 p. 3583-3592
Liver function is measured regularly in liver transplantation (LT) candidates. Currently, these previous disease development data are not used for survival prediction. By constructing and validating joint models (JMs), we aimed to predict the outcome based on all available data, using both disease severity and its rate of change over time. Adult LT candidates listed in Eurotransplant between 2007 and 2018 (n = 16 283) and UNOS between 2016 and 2019 (n = 30 533) were included. Patients with acute liver failure, exception points, or priority status were excluded. Longitudinal MELD(-Na) data were modeled using spline-based mixed effects. Waiting list survival was modeled with Cox proportional hazards models. The JMs combined the longitudinal and survival analysis. JM 90-day mortality prediction performance was compared to MELD(-Na) in the validation cohorts. MELD(-Na) score and its rate of change over time significantly influenced patient survival. The JMs significantly outperformed the MELD(-Na) score at baseline and during follow-up. At baseline, MELD-JM AUC and MELD AUC were 0.94 (0.92–0.95) and 0.87 (0.85–0.89), respectively. MELDNa-JM AUC was 0.91 (0.89–0.93) and MELD-Na AUC was 0.84 (0.81–0.87). The JMs were significantly (p < .001) more accurate than MELD(-Na). After 90 days, we ranked patients for LT based on their MELD-Na and MELDNa-JM survival rates, showing that MELDNa-JM-prioritized patients had three times higher waiting list mortality.
Developing simultaneous liver-kidney transplant medical eligibility criteria while providing a safety net: A 2-year review of the OPTN's allocation policy
Amber R. Wilk,Sarah E. Booker,Darren E. Stewart,Alexander Wiseman,Katrina Gauntt,David Mulligan,Richard N. Formica
doi : 10.1111/ajt.16761
Volume 21, Issue 11 p. 3593-3607
The OPTN's simultaneous liver-kidney (SLK) allocation policy, implemented August 10, 2017, established medical eligibility criteria for adult SLK candidates and created Safety Net kidney allocation priority for liver-alone recipients with new/continued renal impairment. OPTN SLK and kidney after liver (KAL) data were analyzed (registrations as of December 31, 2019, transplants pre-policy [March 20, 2015–August 9, 2017] vs. post-policy [August 10, 2017–December 31, 2019]). Ninety-four percent of SLK registrations met eligibility criteria (99% CKD: 50% dialysis, 50% eGFR). SLK transplant volume decreased from a record 740 (2017) to 676 (2018, ?9%), with a subsequent increase to 728 (2019, 1.6% below 2017 volume). For KAL listings within 1 year of liver transplant, waitlist mortality rates declined post-policy versus pre-policy (27 [95% CI = 20.6–34.7] vs. 16 [11.7–20.5]) while transplant rates increased fourfold (46 [32.2–60.0] vs. 197 [171.6–224.7]). There were 234 KAL transplants post-policy (94% Safety Net priority eligible), and no significant difference in 1-year patient/graft survival vs. kidney-alone (patient: 95.9% KAL, 97.0% kidney-alone [p = .39]; graft: 94.2% KAL, 94.6% kidney-alone [p = .81]). From pre- to post-policy, the proportion of all deceased donor kidney and liver transplants that were SLK decreased (kidney: 5.1% to 4.3%; liver: 9.7% to 8.7%). SLK policy implementation interrupted the longstanding rise in SLK transplants, while Safety Net priority directed kidneys to liver recipients in need with thus far minimal impact to posttransplant outcomes.
Effect of age and care organization on sources of variation in kidney transplant waiting list registration
Cécile Couchoud,Florian Bayer,Muriel Rabilloud,Carole Ayav,Sahar Bayat,Clemence Bechade,Philippe Brunet,Sebastien Gomis,Emilie Savoye,Olivier Moranne,Thierry Lobbedez,Rene Ecochard, on behalf of the REIN registry
doi : 10.1111/ajt.16694
Volume 21, Issue 11 p. 3608-3617
Despite national guidelines, medical practices and kidney transplant waiting list registration policies may differ from one dialysis/transplant unit to another. Benefit risk assessment variations, especially for elderly patients, have also been described. The aim of this study was to identify sources of variation in early kidney transplant waiting list registration in France. Among 16 842 incident patients during the period 2016–2017, 4386 were registered on the kidney transplant waiting list at the start of, or during the first year after starting, dialysis (26%). We developed various log-linear mixed effect regression models on three levels: patients, dialysis networks, and transplant centers. Variability was expressed as variance from the random intercepts (± standard error). Although patient characteristics have an important impact on the likelihood of registration, the overall magnitude of variability in registration was low and shared by dialysis networks and transplant centers. Between-transplant center variability (0.23 ± 0.08) was 1.8 higher than between-dialysis network variability (0.13 ± 0.004). Older age was associated with a lower probability of registration and greater variability between networks (0.04, 0.20, & 0.93 in the 18–64, 65–74, and 75–84 age groups). Targeted interventions should focus on elderly patients and/or certain regions with greater variability in waiting list access.
Improved short-term outcomes of kidney transplants in controlled donation after the circulatory determination of death with the use of normothermic regional perfusion
María Padilla,Elisabeth Coll,Cristina Fernández-Pérez,Teresa Pont,Ángel Ruiz,Marina Pérez-Redondo,Eva Oliver,Lander Atutxa,José M. Manciño,Domingo Daga,Eduardo Miñambres,José Moya,Bárbara Vidal,José M. Dueñas-Jurado,Fernando Mosteiro,Alberto Rodríguez-Salgado,Esperanza Fernández-García,Ramón Lara,Domingo Hernández-Marrero,Belén Estébanez,María Luisa Rodríguez-Ferrero,María Barber,Fernando García-López,Amado Andrés,Carlos Santiago,Ana Zapatero,Rafael Badenes,Francisco Carrizosa,José J. Blanco,José L. Bernal,Francisco J. Elola,Cristina Vidal,Christel Terrón,Pablo Castro,Jordi Comas,Beatriz Domínguez-Gil
doi : 10.1111/ajt.16622
Volume 21, Issue 11 p. 3618-3628
Normothermic regional perfusion (NRP) allows the in situ perfusion of organs with oxygenated blood in donation after the circulatory determination of death (DCDD). We aimed at evaluating the impact of NRP on the short-term outcomes of kidney transplants in controlled DCDD (cDCDD). This is a multicenter, nationwide, retrospective study comparing cDCDD kidneys obtained with NRP versus the standard rapid recovery (RR) technique. During 2012–2018, 2302 cDCDD adult kidney transplants were performed in Spain using NRP (n = 865) or RR (n = 1437). The study groups differed in donor and recipient age, warm, and cold ischemic time and use of ex situ machine perfusion. Transplants in the NRP group were more frequently performed in high-volume centers (?90 transplants/year). Through matching by propensity score, two cohorts with a total of 770 patients were obtained. After the matching, no statistically significant differences were observed between the groups in terms of primary nonfunction (p = .261) and mortality at 1 year (p = .111). However, the RR of kidneys was associated with a significantly increased odds of delayed graft function (OR 1.97 [95% CI 1.43–2.72]; p < .001) and 1-year graft loss (OR 1.77 [95% CI 1.01–3.17]; p = .034). In conclusion, compared with RR, NRP appears to improve the short-term outcomes of cDCDD kidney transplants.
Risk of active tuberculosis infection in kidney transplantation recipients: A matched comparative nationwide cohort study
Sehoon Park,Sanghyun Park,Ji Eun Kim,Mi-Yeon Yu,Yong Chul Kim,Dong Ki Kim,Kwon Wook Joo,Yon Su Kim,Kyungdo Han,Hajeong Lee
doi : 10.1111/ajt.16627
Volume 21, Issue 11 p. 3629-3639
Large-scale evidence comparing the risk of Mycobacterium tuberculosis (TB) between kidney transplant (KT) recipients and dialysis patients is warranted. This is a nationwide retrospective cohort study based on the claims database of South Korea where a moderate prevalence of TB is reported. We included incident KT recipients from 2011 to 2015 and compared their active TB risks with 1:1 matched dialysis and general population control groups, respectively. The risk of incident active TB was assessed by multivariable Cox regression. Associations between active TB and posttransplant death or death-censored graft failure were investigated. The number of matched subjects included in each of the study groups was 7462. The KT group showed a significantly higher risk of active TB than the general population group (hazard ratio [HR] 3.39 [1.88–6.10]), whereas it showed a similar risk to that of the dialysis group (HR 0.98 [0.73–1.31]). In KT patients, active TB was a significant risk factor for both death (HR 2.33 [1.24–4.39]) and death-censored graft failure (HR 2.26 [1.39–3.67]). Although KT recipients may not have to burden the additional risk of active TB when compared with dialysis patients in recent medicine, active TB should not be overlooked as it is associated with a worse prognosis in posttransplant patients.
Association between acute graft pyelonephritis and kidney graft survival: A single-center observational study
Mehdi Maanaoui,Dulciane Baes,Aghilès Hamroun,Kahina Khedjat,Fanny Vuotto,Emmanuel Faure,Benjamin Lopez,Sébastien Bouyé,Thomas Caes,Arnaud Lionet,Céline Lebas,François Provôt,François Glowacki,Jean-Baptiste Gibier,Rémi Lenain,Marc Hazzan
doi : 10.1111/ajt.16703
Volume 21, Issue 11 p. 3640-3648
The association between acute graft pyelonephritis (AGPN) and graft failure in kidney transplant recipients (KTR) remains controversial. In this single-center observational study, we aimed to assess the incidence of AGPN as a time-dependent posttransplantation event. We also examined the association between the diagnosis of AGPN and graft outcomes. In total, we evaluated 1480 patients who underwent kidney transplantation between January 2007 and December 2017. During a median follow-up of 5.04 years, we observed 297 AGPN episodes that occurred in 158 KTR. To evaluate the association between AGPN and clinical outcomes, we performed Cox proportional hazards regression analyses in which AGPN was entered as a time-dependent covariate. AGPN was independently associated with an increased risk of graft loss (hazard ratio = 1.66; 95% confidence interval [CI]: 1.05?2.64, p < .03) and a persistently decreased eGFR (fixed effect on intercept: ?2.29 ml/min/1.73 m2; 95% CI: from ?3.23 to ?1.35, p < .01). However, neither mortality nor biopsy-proven acute rejection was found to correlate with AGPN. Moreover, recurrent AGPN episodes did not appear to have an additive detrimental impact on graft loss. These data represent a promising step in understanding whether AGPN prevention may decrease the risk of graft loss in KTR.
Characterization of ABH-subtype donor-specific antibodies in ABO-A-incompatible kidney transplantation
Andrew Bentall,Mylvaganam Jeyakanthan,Manjit Braitch,Christopher W. Cairo,Todd L. Lowary,Stephanie Maier,Anne Halpin,Bruce Motyka,Lu Zou,Lori J. West,Simon Ball
doi : 10.1111/ajt.16712
Volume 21, Issue 11 p. 3649-3662
ABO-incompatible (ABOi) transplantation requires preemptive antibody reduction; however, the relationship between antibody-mediated rejection (AMR) and ABO-antibodies, quantified by hemagglutination (HA), is inconsistent, possibly reflecting variable graft resistance to AMR or HA assay limitations. Using an ABH-glycan microarray, we quantified ABO-A antigen-subtype (A-subtype)-specific IgM and IgG in 53 ABO-O recipients of ABO-A kidneys, before and after antibody removal (therapeutic plasma exchange [TPE] or ABO-A-trisaccharide immunoadsorption [IA]) and 1-year posttransplant. IgM binding to all A-subtypes correlated highly (R2 ? .90) and A-subtype antibody specificities was reduced equally by IA versus TPE. IgG binding to the A-subtypes (II–IV) expressed in kidney correlated poorly (.27 ? R2 ? .69). Reduction of IgG specific to A-subtype-II was equivalent for IA and TPE, whereas IgG specific to A-subtypes-III/IV was not as greatly reduced by IA (p < .005). One-year posttransplant, IgG specific to A-II remained the most reduced antibody. Immunostaining revealed only A-II on vascular endothelium but A-subtypes II-III/IV on tubular epithelium. These results show that ABO-A-trisaccharide is sufficient for IgM binding to all A-subtypes; this is true for IgG binding to A-II, but not subtypes-III/IV, which exhibits varying degrees of specificity. We identify A-II as the major, but importantly not the sole, antigen relevant to treatment and immune modulation in adult ABO-A-incompatible kidney transplantation.
Hardest-to-place kidney transplant outcomes in the United States
Liise K. Kayler,Jing Nie,Katia Noyes
doi : 10.1111/ajt.16739
Volume 21, Issue 11 p. 3663-3672
The outcomes of hardest-to-place kidney transplants—accepted last in the entire match run after being refused by previous centers—are unclear, potentially translating to risk aversion and unnecessary organ discard. We aimed to determine the outcomes of hardest-to-place kidney transplants and whether the organ acceptance position on the match run sufficiently captures the risk. This is a cohort study of the United Network for Organ Sharing data of all adult kidney-only transplant recipients from deceased donors between 2007 and 2018. Multiple regression models assessed delayed graft function, graft survival, and patient survival stratified by share type: local versus shared kidney acceptance position scaled by tertile. Among 127 028 kidney transplant recipients, 92 855 received local kidneys. The remaining received shared kidneys at sequence number 1–4 (n = 12 322), 5–164 (n = 10 485) and >164 (n = 11 366). Hardest-to-place kidneys, defined as the latest acceptance group in the match-run, were associated with delayed graft function (adjusted odds ratio 1.83, 95% confidence interval [CI] 1.74–1.92) and all-cause allograft failure (adjusted hazard ratio [aHR] 1.11, 95% CI 1.04–1.17). Results of this IRB-approved study were robust to the exclusion of operational allocation bypass and mandatory shares. The hardest-to-place kidneys accepted later in the match run were associated with higher graft failure and delayed graft function.
Outcomes after simultaneous pancreas–kidney transplantation from donation after circulatory death donors: A UK registry analysis
Chris J. Callaghan,Maria Ibrahim,Claire Counter,John Casey,Peter J. Friend,Christopher J. E. Watson,Nikolaos Karydis
doi : 10.1111/ajt.16604
Volume 21, Issue 11 p. 3673-3683
There are concerns that simultaneous pancreas–kidney (SPK) transplants from donation after circulatory death (DCD) donors have a higher risk of graft failure than those from donation after brain death (DBD) donors. A UK registry analysis of SPK transplants between 2005 and 2018 was performed. Pancreas survivals of those receiving organs from DCD or DBD donors were compared. Multivariable analyses were used to adjust for baseline differences between the two groups and to identify factors associated with pancreas graft loss. A total of 2228 SPK transplants were implanted; 403 (18.1%) were from DCD donors. DCD donors were generally younger, slimmer, less likely to have stroke as a cause of death, with lower terminal creatinines and shorter pancreas cold ischemic times than DBD donors. Median (IQR) follow-up was 4.2 (1.6–8.1) years. On univariable analysis, there were no statistically significant differences in 5-year death-censored pancreas graft survival between the two donor types (79.5% versus 80.4%; p = .86). Multivariable analysis showed no statistically significant differences in 5-year pancreas graft loss between transplants from DCD (n = 343) and DBD (n = 1492) donors (hazard ratio 1.26, 95% CI 0.76–1.23; p = .12). The findings from this study support the increased use of SPK transplants from DCD donors.
Between-center variation in high-priority listing status under the new heart allocation policy
Gege Ran,Kevin Chung,Allen S. Anderson,Robert D. Gibbons,Nikhil Narang,Matthew M. Churpek,William F. Parker
doi : 10.1111/ajt.16614
Volume 21, Issue 11 p. 3684-3693
Under the new US heart allocation policy, transplant centers listed significantly more candidates at high priority statuses (Status 1 and 2) with mechanical circulatory support devices than expected. We determined whether the practice change was widespread or concentrated among certain transplant centers. Using data from the Scientific Registry of Transplant Recipients, we used mixed-effect logistic regression to compare the observed listings of adult, heart-alone transplant candidates post-policy (December 2018 to February 2020) to seasonally matched pre-policy cohort (December 2016 to February 2018). US transplant centers (N = 96) listed similar number of candidates in each policy period (4472 vs. 4498) but listed significantly more at high priority status (25.5% vs. 7.0%, p < .001) than expected. Adjusted for candidate characteristics, 91 of 96 (94.8%) centers listed significantly more candidates at high-priority status than expected, with the unexpected increase varying from 4.8% to 50.4% (interquartile range [IQR]: 14.0%–23.3%). Centers in OPOs with highest Status 1A transplant rate pre-policy were significantly more likely to utilize high-priority status under the new policy (OR: 9.73, p = .01). The new heart allocation policy was associated with widespread and significantly variable changes in transplant center practice that may undermine the effectiveness of the new system.
The organ procurement costs of expanding deceased donor organ acceptance criteria: Evidence from a cost function model
Xingxing S. Cheng,Philip J. Held,Avi Dor,Jennifer L. Bragg-Gresham,Jane C. Tan,John D. Scandling,Glenn M. Chertow,John P. Roberts
doi : 10.1111/ajt.16617
Volume 21, Issue 11 p. 3694-3703
A potential solution to the deceased donor organ shortage is to expand donor acceptability criteria. The procurement cost implications of using nonstandard donors is unknown. Using 5 years of US organ procurement organization (OPO) data, we built a cost function model to make cost projections: the total cost was the dependent variable; production outputs, including the number of donors and organs procured, were the independent variables. In the model, procuring one kidney or procuring both kidneys from double/en bloc transplantation from a single-organ donor resulted in a marginal cost of $55 k (95% confidence interval [CI] $28 k, $99 k) per kidney, and procuring only the liver from a single-organ donor results in a marginal cost of $41 k (95% CI $12 k, $69 k) per liver. Procuring two kidneys for two candidates from a donor lowered the marginal cost to $36 k (95% CI $22 k, $66 k) per kidney, and procuring two kidneys and a liver lowers the marginal cost to $24 k (95% CI $17 k, $45 k) per organ. Economies of scale were observed, where high OPO volume was correlated with lower costs. Despite higher cost per organ than for standard donors, kidney transplantation from nonstandard donors remained cost-effective based on contemporary US data.
Predicting donor lung acceptance for transplant during ex vivo lung perfusion: The EX vivo lung PerfusIon pREdiction (EXPIRE)
Matteo Di Nardo,Lorenzo Del Sorbo,Andrew Sage,Jin Ma,Mingyao Liu,Jonathan C. Yeung,Jerome Valero,Rasheed Ghany,Marcelo Cypel,Shaf Keshavjee
doi : 10.1111/ajt.16616
Volume 21, Issue 11 p. 3704-3713
Ex vivo lung perfusion (EVLP) has being increasingly used for the pretransplant assessment of extended-criteria donor lungs. Mathematical models to predict lung acceptance during EVLP have not been reported so far. Thus, we hypothesized that predictors of lung acceptance could be identified and used to develop a mathematical model describing the clinical decision-making process used in our institution. Donor lungs characteristics and EVLP physiologic parameters included in our EVLP registry were examined (derivation cohort). Multivariable logistic regression analysis was performed to identify predictors independently associated with lung acceptance. A mathematical model (EX vivo lung PerfusIon pREdiction [EXPIRE] model) for each hour of EVLP was developed and validated using a new cohort (validation cohort). Two hundred eighty donor lungs were assessed with EVLP. Of these, 186 (66%) were accepted for transplantation. ?PO2 and static compliance/total lung capacity were identified as independent predictors of lung acceptance and their respective cut-off values were determined. The EXPIRE model showed a low discriminative power at the first hour of EVLP assessment (AUC: 0.69 [95% CI: 0.62–0.77]), which progressively improved up to the fourth hour (AUC: 0.87 [95% CI: 0.83–0.92]). In a validation cohort, the EXPIRE model demonstrated good discriminative power, peaking at the fourth hour (AUC: 0.85 [95% CI: 0.76–0.94]). The EXPIRE model may help to standardize lung assessment in centers using the Toronto EVLP technique and improve overall transplant rates.
Targeting CXCR1/2 in the first multicenter, double-blinded, randomized trial in autologous islet transplant recipients
Piotr Witkowski,Martin Wijkstrom,Piotr J. Bachul,Katherine A. Morgan,Marlon Levy,Nicholas Onaca,Sushela S. Chaidarun,Timothy Gardner,A.M. James Shapiro,Andrew Posselt,Syed A. Ahmad,Luisa Daffonchio,Pier A. Ruffini,Melena D. Bellin
doi : 10.1111/ajt.16695
Volume 21, Issue 11 p. 3714-3724
Several cytokines and chemokines are elevated after islet infusion in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT), including CXCL8 (also known as interleukin-8), leading to islet loss. We investigated whether use of reparixin for blockade of the CXCL8 pathway would improve islet engraftment and insulin independence after TPIAT. Adults without diabetes scheduled for TPIAT at nine academic centers were randomized to a continuous infusion of reparixin or placebo (double-blinded) for 7 days in the peri-transplant period. Efficacy measures included insulin independence (primary), insulin dose, hemoglobin A1c (HbA1c), and mixed meal tolerance testing. The intent-to-treat population included 102 participants (age 39.5 ± 12.2 years, 69% female), n = 50 reparixin-treated, n = 52 placebo-treated. The proportion insulin-independent at Day 365 was similar in reparixin and placebo: 20% vs. 21% (p = .542). Twenty-seven of 42 (64.3%) in the reparixin group and 28/45 (62.2%) in the placebo group maintained HbA1c ?6.5% (p = .842, Day 365). Area under the curve C-peptide from mixed meal testing was similar between groups, as were adverse events. In conclusion, reparixin infusion did not improve diabetes outcomes. CXCL8 inhibition alone may be insufficient to prevent islet damage from innate inflammation in islet autotransplantation. This first multicenter clinical trial in TPIAT highlights the potential for future multicenter collaborations.
Ten-year outcomes of islet transplantation in patients with type 1 diabetes: Data from the Swiss-French GRAGIL network
Sandrine Lablanche,Sophie Borot,Anne Wojtusciszyn,Kristina Skaare,Alfred Penfornis,Paolo Malvezzi,Lionel Badet,Charles Thivolet,Emmanuel Morelon,Fanny Buron,Eric Renard,Igor Tauveron,Oriane Villard,Marion Munch,Salomé Sommacal,Léa Clouaire,Morgane Jacquet,Laura Gonsaud,Coralie Camillo-Brault,Cyrille Colin,Jean-Luc Bosson,Domenico Bosco,Thierry Berney,Laurence Kessler,Pierre-Yves Benhamou, on behalf of the GRAGIL Network
doi : 10.1111/ajt.16637
Volume 21, Issue 11 p. 3725-3733
To describe the 10-year outcomes of islet transplantation within the Swiss-French GRAGIL Network, in patients with type 1 diabetes experiencing high glucose variability associated with severe hypoglycemia and/or with functional kidney graft. We conducted a retrospective analysis of all subjects transplanted in the GRAGIL-1c and GARGIL-2 islet transplantation trials and analyzed components of metabolic control, graft function and safety outcomes over the 10-year period of follow-up. Forty-four patients were included between September 2003 and April 2010. Thirty-one patients completed a 10-year follow-up. Ten years after islet transplantation, median HbA1c was 7.2% (6.2–8.0) (55 mmol/mol [44–64]) versus 8.0% (7.1–9.1) (64 mmol/mol [54–76]) before transplantation (p < .001). Seventeen of 23 (73.9%) recipients were free of severe hypoglycemia, 1/21 patients (4.8%) was insulin-independent and median C-peptide was 0.6 ng/ml (0.2–1.2). Insulin requirements (UI/kg/day) were 0.3 (0.1–0.5) versus 0.5 (0.4–0.6) before transplantation (p < .001). Median (IQR) ?-score was 1 (0–4) (p < .05 when comparing with pre-transplantation values) and 51.9% recipients had a functional islet graft at 10 years. With a 10-year follow-up in a multicentric network, islet transplantation provided sustained improvement of glycemic control and was efficient to prevent severe hypoglycemia in almost 75% of the recipients.
Outcomes of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants
Gaurav Gupta,Idris Yakubu,Yiran Zhang,Pamela Kimball,Le Kang,Kimberly Mitchell,Stephen Ijioma,Norman Carroll,Julie Patterson,Meagan Shinbashi,Dhiren Kumar,Irfan Moinuddin,Layla Kamal,Anne King,Chandra Bhati,Marlon Levy,Adrian Cotterell,Aamir Khan,Amit Sharma,Richard Sterling
doi : 10.1111/ajt.16747
Volume 21, Issue 11 p. 3734-3742
Trials describing 4- to 12-week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R? transplants) may be limited in “real-world” application by costs and delayed access to DAAs. We previously reported HCV transmission of 13% among D+/R? transplants with 2- to 4-day pangenotypic sofosbuvir/velpatasvir (SOF/VEL) perioperative prophylaxis, where one patient with HCV transmission was a nonresponder to first-line full-course DAA. Here, we report new data with a 7-day prophylaxis protocol (N = 50), as well as cumulative treatment and outcome data on all HCV D+/R? transplants (N = 102). Overall, nine patients (9/102; 9%; 95% CI: 5%–16%) developed HCV transmission, with a significant decline noted in the 7-day group (2/50; 4%; 95% CI: 0%–13%) compared with 2- to 4-day prophylaxis (7/52; 13%; 95% CI: 5%–25%). All patients with HCV transmission achieved sustained virologic response post full-course therapy (including one nonresponder from initial trial). A 1:1 matched analysis (N = 102) with contemporary HCV D?/R? transplants (controls) showed that although the pretransplant wait time was significantly shorter for D+/R? compared with D?/R? (mean: 1.8 vs. 4.4 years; p < .001), there were no differences in infections, rejection, development of de novo donor-specific antibody, or transplant outcomes up to 6 months of transplant.
Early success transplanting kidneys from donors with new SARS-CoV-2 RNA positivity: A report of 10 cases
Christine E. Koval,Emilio D. Poggio,Yi-Chia Lin,Hannah Kerr,Mohamed Eltemamy,Alvin Wee
doi : 10.1111/ajt.16765
Volume 21, Issue 11 p. 3743-3749
Transplantation of solid organs from donors with active SARS-CoV-2 infection has been advised against due to the possibility of disease transmission to the recipient. However, with the exception of lungs, conclusive data for productive infection of transplantable organs do not exist. While such data are awaited, the organ shortage continues to claim thousands of lives each year. In this setting, we put forth a strategy to transplant otherwise healthy extrapulmonary organs from SARS-CoV-2-infected donors. We transplanted 10 kidneys from five deceased donors with new detection of SARS-CoV-2 RNA during donor evaluation in early 2021. Kidney donor profile index ranged from 3% to 56%. All organs had been turned down by multiple other centers. Without clear signs or symptoms, the veracity of timing of SARS-CoV-2 infection could not be confirmed. With 8–16 weeks of follow-up, outcomes for all 10 patients and allografts have been excellent. All have been free of signs or symptoms of donor-derived SARS-CoV-2 infection. Our findings raise important questions about the nature of SARS-CoV-2 RNA detection in potential organ donors and suggest underutilization of exceptionally good extrapulmonary organs with low risk for disease transmission.
Bariatric surgery prior to transplantation and risk of early hospital re-admission, graft failure, or death following kidney transplantation
Elaine Ku,Charles E. McCulloch,Garrett R. Roll,Andrew Posselt,Barbara A. Grimes,Kirsten L. Johansen
doi : 10.1111/ajt.16779
Volume 21, Issue 11 p. 3750-3757
Bariatric surgery has been shown to be safe in the dialysis population. Whether bariatric surgery before kidney transplantation influences posttransplant outcomes has not been examined nationally. We included severely obese (BMI >35) dialysis patients between 18 and 70 years who received a kidney transplant according to the US Renal Data System. We determined the association between history of bariatric surgery and risk of 30-day readmission, graft failure, or death after transplantation using multivariable logistic, Fine-Gray, and Cox models. We included 12 573 patients, of whom 503 (4%) received bariatric surgery before transplantation. Median age at transplant was 53 years; 42% were women. Overall, history of bariatric surgery was not statistically significantly associated with graft failure (HR 1.02; 95% CI 0.77–1.35) or death (HR 1.10; 95% CI 0.84–1.45). However, sleeve gastrectomy (vs. no bariatric surgery) was associated with lower risk of graft failure (HR 0.39; 95% CI 0.16–0.95). In conclusion, history of bariatric surgery prior to kidney transplantation was not associated with allograft or patient survival, but findings varied by surgery type. Sleeve gastrectomy was associated with better graft survival and should be considered in severely obese transplant candidates receiving dialysis.
Opportunity to increase deceased donation for United States veterans
Brianna L. Doby,Diane Brockmeier,Kevin J. Lee,Christine Jasien,Julia Gallini,Xiangqin Cui,Rebecca H. Zhang,Seth J. Karp,Gary Marklin,Raymond J. Lynch
doi : 10.1111/ajt.16773
Volume 21, Issue 11 p. 3758-3764
Recent changes to organ procurement organization (OPO) performance metrics have highlighted the need to identify opportunities to increase organ donation in the United States. Using data from the Organ Procurement and Transplantation Network (OPTN), Scientific Registry of Transplant Recipients (SRTR), and Veteran Health Administration Informatics and Computing Infrastructure Clinical Data Warehouse (VINCI CDW), we sought to describe historical donation performance at Veteran Administration Medical Centers (VAMCs). We found that over the period 2010–2019, there were only 33 donors recovered from the 115 VAMCs with donor potential nationwide. VA donors had similar age-matched organ transplant yields to non-VA donors. Review of VAMC records showed a total of 8474 decedents with causes of death compatible with donation, of whom 5281 had no infectious or neoplastic comorbidities preclusive to donation. Relative to a single state comparison of adult non-VA inpatient deaths, VAMC deaths were 20 times less likely to be characterized as an eligible death by SRTR. The rate of conversion of inpatient donation-consistent deaths without preclusive comorbidities to actual donors at VAMCs was 5.9% that of adult inpatients at non-VA hospitals. Overall, these findings suggest significant opportunities for growth in donation at VAMCs.
In vivo Treg expansion under costimulation blockade targets early rejection and improves long-term outcome
Christoph Schwarz,Benedikt Mahr,Moritz Muckenhuber,Anna Marianne Weijler,Lukas Walter Unger,Nina Pilat,Michaela Latus,Heinz Regele,Thomas Wekerle
doi : 10.1111/ajt.16724
Volume 21, Issue 11 p. 3765-3774
CTLA4Ig has been shown to improve kidney allograft function, but an increased frequency of early rejection episodes poses a major obstacle for more widespread clinical use. The deleterious effect of CTLA4Ig on Treg numbers provides a possible explanation for graft injury. Therefore, we aimed at improving CTLA4Ig's efficacy by therapeutically increasing the number of Tregs. Murine cardiac allograft transplantation (BALB/c to B6) was performed under CTLA4Ig therapy modeled after the clinically approved dosing regimen and Tregs were transferred early or late after transplant. Neither early nor late Treg transfer prolonged allograft survival. Transferred Tregs were traceable in various lymphoid compartments but only modestly increased overall Treg numbers. Next, we augmented Treg numbers in vivo by means of IL2 complexes. A short course of IL2/anti-IL2-complexes administered before transplantation reversed the CTLA4Ig-mediated decline in Tregs. Of note, the addition of IL2/anti-IL2-complexes to CTLA4Ig therapy substantially prolonged heart allograft survival and significantly improved graft histology on day 100. The depletion of Tregs abrogated this effect and resulted in a significantly diminished allograft survival. The increase in Treg numbers upon IL2 treatment was associated with a decreased expression of B7 on dendritic cells. These results demonstrate that therapy with IL2 complexes improves the efficacy of CTLA4Ig by counterbalancing its unfavorable effect on Tregs.
Sinusoidal obstruction syndrome as a manifestation of acute antibody-mediated rejection after liver transplantation
Carme Baliellas,Laura Lladó,Teresa Serrano,Emma Gonzalez-Vilatarsana,Alba Cachero,Josefina Lopez-Dominguez,Anna Petit,Joan Fabregat
doi : 10.1111/ajt.16689
Volume 21, Issue 11 p. 3775-3779
Antibody-mediated rejection (AMR) after liver transplantation is uncommon but, when present, manifests as graft dysfunction. We report the case of a 54-year-old woman who developed portal hypertension with pleural effusion and ascites secondary to sinusoidal obstruction syndrome (SOS) due to acute AMR following an ABO-matched liver transplantation for autoimmune cirrhosis and hepatocellular carcinoma. Initial immunosuppression comprised basiliximab, decreasing prednisone, tacrolimus, and mycophenolate mofetil. After 1 month, she presented with the massive pleural effusion, slight ascites, and normal liver tests. After excluding common causes of pleural effusion, we performed a liver biopsy that showed atypical rejection with the involvement of large centrilobular veins partially occluded by marked endotheliitis and lax fibrosis suggestive of SOS. Direct immunofluorescence study of C4d showed diffuse endothelial sinusoidal staining, and de novo donor-specific anti-human leukocyte antigen antibodies were detected in his blood. Thus, we diagnosed AMR focused on centrilobular veins and initiated treatment with defibrotide, steroid pulses, and diuretics. However, this was ineffective, and the pleural effusion only resolved when plasmapheresis and intravenous immunoglobulin were started. This case shows that AMR can cause SOS with portal hypertension and present with a pleural effusion, and as such, it should be suspected after excluding other more common causes of effusion.
Donor-derived Cryptococcus gattii sensu stricto infection in two kidney transplant recipients, southeastern United States
Pavithra Natarajan,Shawn R. Lockhart,Sridhar V. Basavaraju,Shweta Anjan,Mark D. Lindsley,Martina M. McGrath,David H. Oh,Brendan R. Jackson
doi : 10.1111/ajt.16729
Volume 21, Issue 11 p. 3780-3784
Cryptococcus gattii infection is a rare cause of severe pulmonary disease and meningoencephalitis that has only recently been detected in the southeastern United States. We describe an organ transplant-associated outbreak of C. gattii infection involving an HIV-negative immunosuppressed donor in this region who died following new-onset headache and seizure of unknown cause. Retrospective cryptococcal antigen (CrAg) testing of donor serum was positive. Two of the three transplant recipients developed severe C. gattii infection 11 and 12 weeks following transplantation. One recipient died from severe pulmonary infection, identified on autopsy, and the other ill recipient survived following treatment for cryptococcal meningitis. This outbreak underscores the importance of considering cryptococcosis in patients with clinical findings suggestive of subacute meningitis or other central nervous system (CNS) pathology, and the potential benefit of routine pre-transplant donor CrAg screening using lateral flow assay to guide recipient antifungal prophylaxis. The case also adds to emerging evidence that C. gattii is a potential threat in the southeastern United States.
Positive flow cytometry crossmatch with discrepant antibody testing results following COVID-19 vaccination
Qingyong Xu,Puneet Sood,Dennis Helmick,Jon S. Lomago,Amit D. Tevar,Adriana Zeevi
doi : 10.1111/ajt.16753
Volume 21, Issue 11 p. 3785-3789
The impact of COVID-19 vaccination on the alloimmunity of transplant candidates is unknown. We report a case of positive B cell flow cytometry crossmatch in a patient waiting for second kidney transplantation, 37 days after receiving the COVID-19 vaccine. The preliminary crossmatch, using sample collected before COVID-19 vaccination, was negative. The antibodies to mismatched donor HLA-DR7 were detected only with multi-antigen beads but not with single-antigen beads, excluding possible prozone effects in solid-phase antibody assays. The crossmatches were positive with HLA-DR7–positive surrogates (n = 2) while negative with HLA-DR7–negative surrogates (n = 3), which confirms the HLA-DR7 alloreactivity. The antigen configurations on B lymphocytes are similar to that on the multi-antigen beads while distinct from the single-antigen beads. HLA-DR7 was the repeating mismatched antigen with the failing first kidney allograft. The newly emerged antibody to HLA-DR7 probably is the consequence of bystander activation of memory response by the COVID-19 vaccination. This case highlights the importance of verifying allo-sensitization history and utilizing multiple assays, including cell-based crossmatch and solid-phase assays with multi-antigens. COVID-19 immunization may deserve special attention when assessing the immunological risk before and after organ transplantation.
Total pancreatectomy with islet cell autotransplantation in a 2-year-old child with hereditary pancreatitis due to a PRSS1 mutation
Braulio A. Marfil-Garza,Joshua Hefler,Khaled Dajani,Tatsuya Kin,A. M. James Shapiro
doi : 10.1111/ajt.16723
Volume 21, Issue 11 p. 3790-3793
Acute recurrent and chronic pancreatitis in children carries high morbidity and burden. Compared to adults, ~75% of the cases of chronic pancreatitis in children are associated with underlying genetic mutations. The decision to intervene and the optimal timing poses unique challenges. Total pancreatectomy and islet cell autotransplantation (TPIAT) provides definitive therapy to relieve pain and improve quality of life while minimizing the risk of pancreatogenic diabetes. Substantial clinical data are available for adults; however, information on clinical outcomes in children remains scarce, particularly for very young children. Herein, we present an unusual, complex case of a 2-year-old child that underwent a successful TPIAT due to hereditary pancreatitis with an underlying mutation in PRSS1 gene, complicated by unremitting pancreatic ascites, hemorrhage, and sepsis. This is the youngest case to be reported in the literature. We provide a comprehensive report of the course and procedures implemented in this patient to guide other teams when considering these extraordinary measures in similar cases.
Trends in nonfatal and fatal overdoses involving benzodiazepines—38 states and the District of Columbia, 2019–2020
Stephen Liu,Julie O’Donnell,R. Matt Gladden,Londell McGlone,Farnaz Chowdhury
doi : 10.1111/ajt.16053
Volume 21, Issue 11 p. 3794-3800
This article describes the significant increase in benzodiazepine-involved overdose deaths between 2019 and 2020, with a particularly notable increase (of over 500%) in deaths related to illicit benzodiazepines (e.g., etizolam, flualprazolam, and flubromazolam). The vast majority of benzodiazepine-involved overdose deaths also involved opioids, particularly illicitly manufactured fentanyls. This increase in benzodiazepine-involved overdose deaths has likely contributed to the deceased donor pool.
Multiple liver lesions in a lung transplant recipient
Madeleine R. Heldman,Chris Chandler,Joshua A. Lieberman,Ajit P. Limaye
doi : 10.1111/ajt.16721
Volume 21, Issue 11 p. 3801-3803
Successful transplantation of organs from a deceased donor with early SARS-CoV-2 infection
Abhay Dhand,Alan Gass,Seigo Nishida,Masashi Kai,Karen Berger,David Wolf,Suguru Ohira,Hiroshi Sogawa,Leslie Lee,Edward Lebovics,Chad Ezzell,Thomas Diflo,David Spielvogel,Rifat Latifi,Amy L. Friedman
doi : 10.1111/ajt.16706
Volume 21, Issue 11 p. 3804-3805
Serological response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients depends on prior exposure to SARS-CoV-2
Louis Firket,Julie Descy,Laurence Seidel,Catherine Bonvoisin,Antoine Bouquegneau,Stéphanie Grosch,François Jouret,Laurent Weekers
doi : 10.1111/ajt.16726
Volume 21, Issue 11 p. 3806-3807
Strong antibody response after a first dose of a SARS-CoV-2 mRNA-based vaccine in kidney transplant recipients with a previous history of COVID-19
Ilies Benotmane,Gabriela Gautier -Vargas,Floriane Gallais,Pierre Gantner,Noëlle Cognard,Jérôme Olagne,Aurélie Velay,Françoise Heibel,Laura Braun-Parvez,Jonas Martzloff,Peggy Perrin,Bruno Moulin,Samira Fafi-Kremer,Sophie Caillard
doi : 10.1111/ajt.16764
Volume 21, Issue 11 p. 3808-3810
Tests for the noninvasive diagnosis of kidney transplant rejection should be evaluated by kidney transplant programs
Gabriel M. Danovitch,Suphamai Bunnapradist,David Cohen,Sundaram Hariharan,Dianne McKay,Lloyd Ratner,Mark D. Stegall,Robert W. Steiner,Peter G. Stock,Flavio Vincenti
doi : 10.1111/ajt.16711
Volume 21, Issue 11 p. 3811-3811
Challenging the notion of conflict of interest in transplantation: Barriers at the intersection between innovation and clinical advancement
Oscar K. Serrano,Laurence Turka,David A. Axelrod
doi : 10.1111/ajt.16763
Volume 21, Issue 11 p. 3812-3813
Warm ischemia time influences human islet cell isolation yield when assessed as beta cell number but not as islet equivalent number
Diedert L. De Paep,Daniel Jacobs-Tulleneers-Thevissen
doi : 10.1111/ajt.16691
Volume 21, Issue 11 p. 3814-3815
