Transplant InternationalPub Date : 2024-10-07eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13491
Joachim Denner
{"title":"Monitoring for PERV Following Xenotransplantation.","authors":"Joachim Denner","doi":"10.3389/ti.2024.13491","DOIUrl":"https://doi.org/10.3389/ti.2024.13491","url":null,"abstract":"<p><p>Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs. PERV-A, PERV-B and PERV-C can be released as infectious virus particles and PERV-A and PERV-B can infect human cells in culture. PERV-C does not infect human cells, but high-titer recombinant PERV-A/C can infect them. Retroviruses are able to induce immunosuppression and/or tumors in the infected host. Numerous methods have been developed to study PERV in donor pigs. No PERV infections were observed in infection experiments as well as in preclinical and clinical xenotransplantation trials. Despite this, several strategies have been developed to prevent PERV infection of the recipient. PCR-based and immunological methods are required to screen xenotransplant recipients. Since the proviruses are integrated into the pig genome, PERV infection has to be distinguished from microchimerism, e.g., the presence of pig cells in the recipient, which is common in xenotransplantation. Sensitive PCR methods using pig short interspersed nuclear elements (SINE) sequences allow to detect pig cells easily. Virus infection can also be detected by an increase of viral genomic or mRNA in human cells. The method of choice, however, is to screen for specific antibodies against PERV using different recombinant PERV proteins, purified viruses or peptides.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-10-02eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.12803
Paolo A Grossi, Cameron Wolfe, Maddalena Peghin
{"title":"Non-Standard Risk Donors and Risk of Donor-Derived Infections: From Evaluation to Therapeutic Management.","authors":"Paolo A Grossi, Cameron Wolfe, Maddalena Peghin","doi":"10.3389/ti.2024.12803","DOIUrl":"https://doi.org/10.3389/ti.2024.12803","url":null,"abstract":"<p><p>Expected and unexpected donor-derived infections are a rare complication of solid organ transplantation, but can result in significant morbidity and mortality. Over the last years, the growing gap existing between patients on the waiting list and available organs has favored the use of organs from donors with suspected or confirmed infections, thanks to the improvement of risk mitigation strategies against transmission of well recognized and emerging infections. Given the recent developments, the particular interest of this review is to summarize data on how to maximize utilization of HIV+ donors in HIV+ recipients, the use of HCV-viremic donors and HBV positive donors. This article also covers the implications for recipient of organs from donors with bacteremia and the challenge of multidrug resistant (MDR) infections. Lastly this review describes emerging risks associated with recent Coronavirus Disease-2019 (COVID-19) pandemics.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-09-27eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13607
Matthias Längin, Martin Bender, Michael Schmoeckel, Bruno Reichart
{"title":"Progress in Orthotopic Pig Heart Transplantation in Nonhuman Primates.","authors":"Matthias Längin, Martin Bender, Michael Schmoeckel, Bruno Reichart","doi":"10.3389/ti.2024.13607","DOIUrl":"https://doi.org/10.3389/ti.2024.13607","url":null,"abstract":"<p><p>Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6-9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-09-26eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.12920
Michaela Matysková Kubišová, Sylvie Dusilová Sulková, Petr Moučka, Anita Pokorná, Marcela Heislerová, Igor Guňka, Pavel Navrátil, Jaroslav Pacovský, Alena Malá, Roman Šafránek
{"title":"Management of Kidney Transplant Outpatients With COVID-19: A Single Center Experience.","authors":"Michaela Matysková Kubišová, Sylvie Dusilová Sulková, Petr Moučka, Anita Pokorná, Marcela Heislerová, Igor Guňka, Pavel Navrátil, Jaroslav Pacovský, Alena Malá, Roman Šafránek","doi":"10.3389/ti.2024.12920","DOIUrl":"10.3389/ti.2024.12920","url":null,"abstract":"<p><p>Patients undergoing kidney transplant are at risk of severe COVID-19. Our single-center retrospective analysis evaluated the outcomes of kidney transplant outpatients with COVID-19 who were managed with reduced immunosuppression and treatment with molnupiravir. Between January 2022 and May 2023, we included 93 patients (62 men, average age 56 years), serum creatinine 127 (101-153) µmol/L. Molnupiravir was administered, and immunosuppressive therapy was reduced immediately following the confirmation of SARS-CoV-2 infection by PCR, which was 2 (1-3) days after the onset of symptoms. Only three (3.2%) patients required hospitalization, and one patient died. Acute kidney injury was observed in two patients. During the follow-up period of 19 (15-22) months, there was no significant increase in proteinuria, no acute or new chronic graft rejection, and kidney graft function remained stable; serum creatinine was 124 (106-159) µmol/L post-COVID-19 infection and 128 (101-161) µmol/L at the end of the follow-up period. Our results demonstrate that early initiation of molnupiravir treatment combined with a temporary reduction in immunosuppressive therapy results in favorable clinical outcomes in patients with COVID-19, with preservation of good graft function and no episodes of graft rejection.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-09-23eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13302
Samrat Ray, Christian Hobeika, Andrea Norgate, Zaneta Sawicka, Jeffrey Schiff, Gonzalo Sapisochin, Ian D McGilvray, Markus Selzner, Trevor W Reichman, Chaya Shwaartz
{"title":"Evolving Trends in the Management of Duodenal Leaks After Pancreas Transplantation: A Single-Centre Experience.","authors":"Samrat Ray, Christian Hobeika, Andrea Norgate, Zaneta Sawicka, Jeffrey Schiff, Gonzalo Sapisochin, Ian D McGilvray, Markus Selzner, Trevor W Reichman, Chaya Shwaartz","doi":"10.3389/ti.2024.13302","DOIUrl":"https://doi.org/10.3389/ti.2024.13302","url":null,"abstract":"<p><p>Duodenal leaks (DL) contribute to most graft losses following pancreas transplantation. However, there is a paucity of literature comparing graft preservation approach versus upfront graft pancreatectomy in these patients. We reviewed all pancreas transplants performed in our institution between 2000 and 2020 and identified the recipients developing DL to compare based on their management: percutaneous drainage vs. operative graft preservation vs. upfront pancreatectomy. Of the 595 patients undergoing pancreas transplantation, 74 (12.4%) developed a duodenal leak with a median follow up of 108 months. Forty-five (61%) were managed by graft preservation strategies, with the rest being treated with upfront graft pancreatectomy. DL managed by graft preservation strategies had similar graft survival rates at 1 and 5-year compared to the matched cohort of population without DL (95% and 59% vs. 91% and 62%; p = 0.78). Multivariate analysis identified male recipient (OR: OR: 6.18; CI95%: 1.26-41.09; p = 0.04) to have higher odds of undergoing an upfront graft pancreatectomy. In appropriately selected recipients with DL, graft preservation strategies utilizing either interventional radiology guided percutaneous drainage or laparotomy with/without repair of leak can achieve comparable long-term graft survival rates compared to recipients without DL.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-09-20eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13173
Henrik Benoni, Caroline Nordenvall, Vivan Hellström, Caroline E Dietrich, Anna Martling, Karin E Smedby, Sandra Eloranta
{"title":"Previous Solid Organ Transplantation Influences Both Cancer Treatment and Survival Among Colorectal Cancer Patients.","authors":"Henrik Benoni, Caroline Nordenvall, Vivan Hellström, Caroline E Dietrich, Anna Martling, Karin E Smedby, Sandra Eloranta","doi":"10.3389/ti.2024.13173","DOIUrl":"10.3389/ti.2024.13173","url":null,"abstract":"<p><p>Previous solid organ transplantation has been associated with worse survival among colorectal cancer (CRC) patients. This study investigates the contribution of CRC characteristics and treatment-related factors to the differential survival. Using the Swedish register-linkage CRCBaSe, all patients with solid organ transplantation before CRC diagnosis were identified and matched with non-transplanted CRC patients. Associations between transplantation history and clinical CRC factors and survival were estimated using the Kaplan-Meier estimator and logistic, multinomial, and Cox regression, respectively. Ninety-eight transplanted and 474 non-transplanted CRC patients were followed for 5 years after diagnosis. Among patients with stage I-III cancer, transplanted patients had lower odds of treatment with abdominal surgery [odds ratio (OR):0.27, 95% confidence interval (CI):0.08-0.90], than non-transplanted patients. Among those treated with surgery, transplanted colon cancer patients had lower odds of receiving adjuvant chemotherapy (OR:0.31, 95% CI:0.11-0.85), and transplanted rectal cancer patients had higher rate of relapse (hazard ratio:9.60, 95% CI:1.84-50.1), than non-transplanted patients. Five-year cancer-specific and overall survival was 56% and 35% among transplanted CRC patients, and 68% and 57% among non-transplanted. Accordingly, transplanted CRC patients were treated less intensely than non-transplanted patients, and had worse cancer-specific and overall survival. These patients might benefit from multidisciplinary evaluation including transplantation specialists.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-09-19eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13087
Eric J Martinez, Phuoc H Pham, Jesse F Wang, Lily N Stalter, Bridget M Welch, Glen Leverson, Nicholas Marka, Talal Al-Qaoud, Didier Mandelbrot, Sandesh Parajuli, Hans W Sollinger, Dixon B Kaufman, Robert R Redfield, Jon Scott Odorico
{"title":"Analysis of Rejection, Infection and Surgical Outcomes in Type I Versus Type II Diabetic Recipients After Simultaneous Pancreas-Kidney Transplantation.","authors":"Eric J Martinez, Phuoc H Pham, Jesse F Wang, Lily N Stalter, Bridget M Welch, Glen Leverson, Nicholas Marka, Talal Al-Qaoud, Didier Mandelbrot, Sandesh Parajuli, Hans W Sollinger, Dixon B Kaufman, Robert R Redfield, Jon Scott Odorico","doi":"10.3389/ti.2024.13087","DOIUrl":"10.3389/ti.2024.13087","url":null,"abstract":"<p><p>Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HR<sub>pancreas</sub> = 1.04, p = 0.93; HR<sub>kidney</sub> = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (p<sub>pancreas</sub> = 0.57; p<sub>kidney</sub> = 0.41). T2D had a significantly lower incidence of <i>de novo</i> DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-09-19eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13010
Lisa Kleid, Julia Walter, Patrick Moehnle, Christian Wichmann, Julia Kovács, Andreas Humpe, Christian Schneider, Sebastian Michel, Nikolaus Kneidinger, Michael Irlbeck, Jan Fertmann, Andrea Dick, Teresa Kauke
{"title":"High-Risk HLA-DQ Mismatches Are Associated With Adverse Outcomes After Lung Transplantation.","authors":"Lisa Kleid, Julia Walter, Patrick Moehnle, Christian Wichmann, Julia Kovács, Andreas Humpe, Christian Schneider, Sebastian Michel, Nikolaus Kneidinger, Michael Irlbeck, Jan Fertmann, Andrea Dick, Teresa Kauke","doi":"10.3389/ti.2024.13010","DOIUrl":"https://doi.org/10.3389/ti.2024.13010","url":null,"abstract":"<p><p>Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students' t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (<i>p</i> = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (<i>p</i> = 0.03) and CLAD (<i>p</i> = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-09-19eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13431
Jennifer K McDermott, Skye J Castaneda, Sarah M Mietz, Cameron K Lawson, John A Gerlach, Ryan J Hadley, Gayathri Sathiyamoorthy, Sheila Krishnan, Edward T Murphy, Reda E Girgis
{"title":"Preemptive Treatment of De Novo Donor Specific Anti-HLA Antibodies With IVIG Monotherapy after Lung Transplantation.","authors":"Jennifer K McDermott, Skye J Castaneda, Sarah M Mietz, Cameron K Lawson, John A Gerlach, Ryan J Hadley, Gayathri Sathiyamoorthy, Sheila Krishnan, Edward T Murphy, Reda E Girgis","doi":"10.3389/ti.2024.13431","DOIUrl":"10.3389/ti.2024.13431","url":null,"abstract":"","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}