Genetic diversity, growth and heart function of Auckland Island pigs, a potential source for organ xenotransplantation.

One of the prerequisites for successful organ xenotransplantation is a reasonable size match between the porcine organ and the recipient's organ to be replaced. Therefore, the selection of a suitable genetic background of source pigs is important. In this study, we investigated body and organ growth, cardiac function, and genetic diversity of a colony of Auckland Island pigs established at the Center for Innovative Medical Models (CiMM), LMU Munich. Male and female Auckland Island pig kidney cells (selected to be free of porcine endogenous retrovirus C) were imported from New Zealand, and founder animals were established by somatic cell nuclear transfer (SCNT). Morphologically, Auckland Island pigs have smaller body stature compared to many domestic pig breeds, rendering their organ dimensions well-suited for human transplantation. Furthermore, echocardiography assessments of Auckland Island pig hearts indicated normal structure and functioning across various age groups throughout the study. Single nucleotide polymorphism (SNP) analysis revealed higher runs of homozygosity (ROH) in Auckland Island pigs compared to other domestic pig breeds and demonstrated that the entire locus coding the swine leukocyte antigens (SLAs) was homozygous. Based on these findings, Auckland Island pigs represent a promising genetic background for organ xenotransplantation.

Policies and practice of solid organ donation amongst people living with HIV in Canada: time for education and re-evaluation.

The numbers of organ donors in Canada and the USA fall short of increasing demand, resulting in increased morbidity, poor health outcomes, higher medical costs and death of many individuals waitlisted for transplantation. In the US, since 2013 when the US HIV Organ Policy Equity (HOPE) Act lifted the ban on organ donation between people living with HIV, the option of using organs from People with HIV became a reality. In Canada, HIV diagnosis was an exclusion criterion to organ donation until 2017, when permission was granted if requirements for 'exceptional distribution' could be met. Still, donation of organs from people with HIV poses challenges. Herein, we overview policies involving donors with HIV in Canada in order to inform healthcare providers, researchers and the community. We also advocate for the need to reassess these policies, highlight educational needs and engage interest in advancing research to inform policy reforms.

Innovative surgical techniques in the intestine and multivisceral transplant.

PURPOSE OF REVIEW: This timely review delves into the evolution of multivisceral transplantation (MVT) over the past six decades underscoring how advancements in surgical techniques and immunosuppression have driven transformation, to provide insight into the historical development of MVT, shedding light on its journey from experimentation to a valuable clinical approach. RECENT FINDINGS: The review presents contemporary enhancements in surgical methods within the context of intestinal transplantation. The versatility of MVT is emphasized, accommodating diverse organ combinations and techniques. Both isolated intestinal transplantation (IIT) and MVT have seen expanded indications, driven by improved parenteral nutrition, transplantation outcomes, and surgical innovations. Surgical techniques are tailored based on graft type, with various approaches for isolated transplantation. Preservation strategies and ostomy techniques are also covered, along with graft assessment advancements involving donor-specific antibodies. SUMMARY: This review's findings underscore the remarkable evolution of MVT from experimental origins to a comprehensive clinical practice. The progress in surgical techniques and immunosuppression has broadened the spectrum of patients who can benefit from intestinal transplant, including both IIT and MVT. The expansion of indications offers hope to patients with complex gastrointestinal disorders. The detection of donor-specific antibodies in graft assessment advances diagnostic accuracy, ultimately improving patient outcomes.

Ex Vivo Gene Therapy in Organ Transplantation: Considerations and Clinical Translation.

Ex vivo machine perfusion (EVMP) is rapidly growing in utility during solid organ transplantation. This form of organ preservation is transforming how organs are allocated and expanding the definition of what is considered a suitable organ for transplantation in comparison with traditional static cold storage. All major organs (heart, lung, liver, kidney) have been influenced by this advanced method of organ preservation. This technology also serves as an unprecedented platform for effective administration of advanced therapeutics, including gene therapies, during organ transplantation to optimize and recondition organs ex vivo in an isolated manner. Applying gene therapy interventions through EVMP introduces different considerations and challenges that are unique from gene therapies designed for systemic administration. Considerations involving vector (choice, dose, toxicity), perfusate composition, and perfusion circuit components should be evaluated when developing a gene therapy to administer in this setting. This review explores these aspects and discusses clinical applications in transplantation where gene therapy interventions can be developed relevant to heart, lung, liver, and kidney donor grafts.

Rapid antimicrobial resistance detection methods for bloodstream infection in solid organ transplantation: Proposed clinical guidance, unmet needs, and future directions.

Recent advances in antimicrobial resistance detection have spurred the development of multiple assays that can accurately detect the presence of bacterial resistance from positive blood cultures, resulting in faster institution of effective antimicrobial therapy. Despite these advances, there are limited data regarding the use of these assays in solid organ transplant (SOT) recipients and there is little guidance on how to select, implement, and interpret them in clinical practice. We describe a practical approach to the implementation and interpretation of these assays in SOT recipients using the best available data and expert opinion. These findings were part of a consensus conference sponsored by the American Society of Transplantation held on December 7, 2021 and represent the collaboration between experts in transplant infectious diseases, pharmacy, antimicrobial and diagnostic stewardship, and clinical microbiology. Areas of unmet need and recommendations for future investigation are also presented.

Normothermic Regional Perfusion-The Next Frontier in Organ Transplants?

This Viewpoint examines an approach known as normothermic regional perfusion, involving use of ECMO to restore perfusion to internal organs in situ before they are removed from a deceased donor.

Skin and gut microbial associations with squamous cell carcinoma in solid organ transplant recipients.

Solid organ transplant recipients (SOTRs) are burdened with a significantly higher risk of squamous cell carcinoma (SCC) compared to the general population. Accumulating evidence suggests the potential influence of microbial dysbiosis on transplant outcomes. Based on these observations, we sought to identify differences in the cutaneous and gut microbiomes of SOTRs with and without a history of SCC. This case-control study collected and analyzed non-lesional skin and fecal samples of 20 SOTRs > 18 years old with either ≥ 4 diagnoses of SCC since most recent transplant (n = 10) or 0 diagnoses of SCC (n = 10). The skin and gut microbiomes were investigated with Next-Generation Sequencing, and analysis of variance (ANOVA) followed by Tukey pairwise comparison procedure was used to test for differences in taxonomic relative abundances and microbial diversity indices between the two cohorts. Analyses of the skin microbiome showed increased bacterial and reduced fungal diversity in SOTRs with a history of SCC compared to SOTRs without a history of SCC (bacterial median Shannon diversity index (SDI) = 3.636 and 3.154, p < 0.05; fungal SDI = 4.474 and 6.174, p < 0.05, respectively). Analyses of the gut microbiome showed reduced bacterial and fungal diversity in the SCC history cohort compared to the SCC history-negative cohort (bacterial SDI = 2.620 and 3.300, p < 0.05; fungal SDI = 3.490 and 3.812, p < 0.05, respectively). The results of this pilot study thus show a trend toward the bacterial and fungal communities of the gut and skin being distinct in SOTRs with a history of SCC compared to SOTRs without a history of SCC. It furthermore demonstrates the potential for microbial markers to be used in the prognostication of squamous cell carcinoma risk in solid organ transplant recipients.

Partial heart xenotransplantation: A research protocol in non-human primates.

Partial heart transplantation is a new type of transplant that delivers growing heart valve replacements for babies. Partial heart transplantation differs from orthotopic heart transplantation because only the part of the heart containing the heart valve is transplanted. It also differs from homograft valve replacement because viability of the graft is preserved by tissue matching, minimizing donor ischemia times, and recipient immunosuppression. This preserves partial heart transplant viability and allows the grafts to fulfill biological functions such as growth and self-repair. These advantages over conventional heart valve prostheses are balanced by similar disadvantages as other organ transplants, most importantly limitations in donor graft availability. Prodigious progress in xenotransplantation promises to solve this problem by providing an unlimited source of donor grafts. In order to study partial heart xenotransplantation, a suitable large animal model is important. Here we describe our research protocol for partial heart xenotransplantation in nonhuman primates.

Surgical Approach, Challenges, and Resolutions for Uterus Transplantation in Rats.

Uterine transplantation (UTx) is a new approach for treating women with absolute uterine factor infertility (AUFI). An estimated 3%-5% of women suffer from AUFI. These women were deprived of the option to have children until the advent of UTx. The clinical application of UTx was driven by experimental studies in animals, and the first successful UTx was achieved in rats. Given their physiological, immunological, genetic, and reproductive characteristics, rats are a suitable model system for such transplants. In particular, their short gestation period is a clear advantage, as the usual endpoint of experimental UTx is successful pregnancy with live birth. The biggest challenge for rat models remains the small anatomy, which requires advanced microsurgical skills and experience. Although UTx has led to pregnancy in the clinic, the procedure is not established and requires continuous experimental optimization. Here, a detailed protocol is presented, including essential troubleshooting for rat UTx, which is expected to make the entire procedure easier to grasp for those without experience in this type of microsurgery.

Assessing the impact of COVID-19 on the performance of organ transplant services using data envelopment analysis.

Organ transplant is one of the best options for many medical conditions, and in many cases, it may be the only treatment option. Recent evidence suggests, however, that the COVID-19 pandemic might have detrimentally affected the provision of this type of healthcare services. The main purpose of this article is to use Data Envelopment Analysis and the Malmquist Index to assess the impact that the pandemic caused by the novel coronavirus SARS-CoV-2 had on the provision of solid organ transplant services. To this purpose, we use three complementary models, each focusing on specific aspects of the organ donation and transplantation process, and data from Brazil, which has one of the most extensive public organ transplant programs in the world. Using data from 17 States plus the Federal District, the results of our analysis show a significant drop in the performance of the services in terms of the organ donation and transplantation process from 2018 to 2020, but the results also indicate that not all aspects of the process and States were equally affected. Furthermore, by using different models, this research also allows us to gain a more comprehensive and informative assessment of the performance of the States in delivering this type of service and identify opportunities for reciprocal learning, expanding our knowledge on this important issue and offering opportunities for further research.

Best practices during COVID-19 pandemic in solid organ transplant programs in Spain.

Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc. The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units. The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n = 9), peritransplant period (n = 7), postransplant period (n = 8) and training and communication (n = 6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered. Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation.

Human Tracheal Transplantation.

Long-segment tracheal airway defects may be congenital or result from burns, trauma, iatrogenic intubation damage, or tumor invasion. Although airway defects <6 cm in length may be reconstructed using existing end-to-end reconstructive techniques, defects >6 cm continue to challenge surgeons worldwide. The reconstruction of long-segment tracheal defects has long been a reconstructive dilemma, and these defects are associated with significant morbidity and mortality. Many of these defects are not compatible with life or require a permanent extended-length tracheostomy that is fraught with complications including mucus plugging and tracheoesophageal fistula. Extensive circumferential tracheal defects require a reconstructive technique that provides a rigid structure able to withstand the inspiratory pressures, a structure that will biologically integrate, and contain functional ciliated epithelium to allow for normal mucociliary clearance. Tracheal transplantation has been considered the reconstructive "Holy Grail;" however, there has been a long-held scientific dogma that revascularization of the trachea was not possible. This dogma stifled research to achieve single-staged vascularized tracheal transplantation and prompted the introduction of many creative and inventive alternatives. Throughout history, alloplastic material, nonvascularized allografts, and homografts have been used to address this dilemma. However, these techniques have largely been unsuccessful. The recent introduction of a technique for single-staged vascularized tracheal transplantation may offer a solution to this dilemma and potentially a solution to management of the fatal tracheoesophageal fistula.

Pathogen-agnostic immune biomarkers that predict infection after solid organ transplantation.

Solid organ transplant recipients (SOTRs) remain at high risk for infection throughout their post-transplant course. Dosing of immunosuppressive medications, strategies that prevent infection, and choice of empiric antimicrobial treatment could be optimized by a better understanding of an individual patient's risk for infectious complications. Diagnostic tests that qualitatively or quantitatively measure the function of the immune system and/or its response to infection may be useful for individualized management decisions. Numerous studies have identified an association between infectious outcomes after solid organ transplantation (SOT) and the results of a variety of non-pathogen-specific or "pathogen-agnostic" immune monitoring tests. These biomarkers include humoral immune markers, functional or quantitative assessments of cellular immunity, transcriptomic-based diagnostics, and replication of viruses within the human virome, which have been used to predict or diagnose a variety of different infectious diseases complicating SOT. In this narrative review, we discuss several host-derived immune biomarkers that show promise for either predicting or diagnosing infection among SOTRs. However, additional studies are needed to determine the optimal use of immune response testing. Whether immune biomarkers contribute added benefits to current standard clinical care has not yet been determined. Testing must be validated across a range of clinical scenarios, including surveillance to predict infection risk and diagnosis of active infection at various time points post transplant.

Revisiting transplant immunology through the lens of single-cell technologies.

Solid organ transplantation (SOT) is the standard of care for end-stage organ disease. The most frequent complication of SOT involves allograft rejection, which may occur via T cell- and/or antibody-mediated mechanisms. Diagnosis of rejection in the clinical setting requires an invasive biopsy as there are currently no reliable biomarkers to detect rejection episodes. Likewise, it is virtually impossible to identify patients who exhibit operational tolerance and may be candidates for reduced or complete withdrawal of immunosuppression. Emerging single-cell technologies, including cytometry by time-of-flight (CyTOF), imaging mass cytometry, and single-cell RNA sequencing, represent a new opportunity for deep characterization of pathogenic immune populations involved in both allograft rejection and tolerance in clinical samples. These techniques enable examination of both individual cellular phenotypes and cell-to-cell interactions, ultimately providing new insights into the complex pathophysiology of allograft rejection. However, working with these large, highly dimensional datasets requires expertise in advanced data processing and analysis using computational biology techniques. Machine learning algorithms represent an optimal strategy to analyze and create predictive models using these complex datasets and will likely be essential for future clinical application of patient level results based on single-cell data. Herein, we review the existing literature on single-cell techniques in the context of SOT.

Serologic follow-up of solid organ transplant recipients who received organs from donors with reactive syphilis tests: A retrospective cohort study.

The increased procurement of organs from donors with risk factors for blood-borne diseases and the expanding syphilis epidemic have resulted in a growing number of organs transplanted from donors with reactive syphilis serology in our center. Based on guidelines, recipients typically receive therapy shortly after the transplant, but data on outcomes are limited. The primary objective of this study was to determine syphilis seroconversion rates at three months post-transplant in recipients of solid organs procured from donors with reactive syphilis serology. Organ donors and recipients were tested for syphilis antibody; positive results were confirmed with Treponema pallidum Particle Agglutination (TPPA). Eleven donors with reactive syphilis antibody donated organs to 25 syphilis negative recipients. Three recipients seroconverted at post-transplant month 3. All of them had received therapy shortly after transplant. TPPA was negative in all 3. Despite post-transplant treatment, 3 of 25 (12%) syphilis negative recipients of organs from syphilis positive donors seroconverted at 3 months. All remained TPPA negative possibly reflecting passive antibody transfer or differing test sensitivity to low level treponemal antibodies. Further studies are needed to assess optimal syphilis transmission prevention strategies and follow up recipient testing in organ transplantation.

Software para apoio à decisão logística no processo de captação e transplante de órgãos / Software de apoyo a la decisión logística en el proceso de obtención y trasplante de órganos / Software to support logistic decision in the process of organ acquisition and transplantation

Objetivo: desenvolver e avaliar um software para apoio à tomada de decisão dos profissionais da central de transplantes nas definições logísticas envolvidas no processo de captação e distribuição de órgãos para transplante. Método: estudo de produção tecnológica aplicada, sustentado pelo método Design Science Research Methodology. Participaram da etapa de avaliação da usabilidade dez enfermeiros da Central de Transplantes de Santa Catarina. A coleta de dados ocorreu de 1 a 20 de julho de 2021 por meio do questionário System Usability Scale. Resultados: o software utilizou linguagem JavaScript com ReactJS e PHP com Laravel, para o banco de dados PostgreSQL. A avaliação obteve escore médio de 98,25, sendo sua usabilidade considerada como melhor alcançável. Conclusão: o software demonstrou ser adequado e funcional, com fácil manuseio, reunindo informações integradas e objetivas. Representa um avanço na área, propondo uma inovação tecnológica para a gestão e apoio às decisões logísticas envolvidas no processo de captação e transplante de órgãos.

Objetivo: desenvolver e avaliar um software para apoio à tomada de decisão dos profissionais da central de transplantes nas definições logísticas envolvidas no processo de captação e distribuição de órgãos para transplante. Método: estudo de produção tecnológica aplicada, sustentado pelo método Design Science Research Methodology. Participaram da etapa de avaliação da usabilidade dez enfermeiros da Central de Transplantes de Santa Catarina. A coleta de dados ocorreu de 1 a 20 de julho de 2021 por meio do questionário System Usability Scale. Resultados: o software utilizou linguagem JavaScript com ReactJS e PHP com Laravel, para o banco de dados PostgreSQL. A avaliação obteve escore médio de 98,25, sendo sua usabilidade considerada como melhor alcançável. Conclusión: o software demonstrou ser adequado e funcional, com fácil manuseio, reunindo informações integradas e objetivas. Representa um avanço na área, propondo uma inovação tecnológica para a gestão e apoio às decisões logísticas envolvidas no processo de captação e transplante de órgãos.

Objective: to develop and evaluate a software to support the decision-making of transplant center professionals in the logistic definitions involved in the process of organ procurement and distribution for transplantation. Method: applied technological production study, supported by the Design Science Research Methodology method. Ten nurses from the Transplant Center of Santa Catarina participated in the usability evaluation stage. Data collection took place from 1 to 20 July 2021 through the System Usability Scale questionnaire. Results: the software used JavaScript language with ReactJS and PHP with Laravel, for the PostgreSQL database. The evaluation obtained a mean score of 98.25, and its usability is considered as best achievable. Conclusion: the software proved to be adequate and functional, with easy handling, gathering integrated and objective information. It represents a breakthrough in the area, proposing a technological innovation for the management and support to the logistic decisions involved in the process of organ procurement and transplantation.

Rapid molecular testing for antimicrobial stewardship and solid organ transplantation.

BACKGROUND: Several molecular platforms now exist for early detection of infectious pathogens. In this review, we present the currently available literature summarizing clinical outcomes using rapid diagnostic tests (RDTs) in the solid organ transplant (SOT) population. We also present potential benefits and drawbacks of these technologies for SOT patients. METHODS: We completed a PubMed search querying for 31 specific RDTs AND ("SOT"). We also queried PubMed for studies on RDT outcomes in the general population. References of the resulting relevant studies were reviewed and incorporated if the study population included at least one SOT patient. All culture specimen types were included. Only full-text peer-reviewed publications in English were examined. RESULTS: Our search yielded eleven studies. Across these studies, integrating RDTs with ASP intervention led to faster species identification and susceptibility results, faster time-to-optimal therapy, decreased hospital length-of-stay and costs, and decreased mortality. Potential drawbacks of RDTs in the SOT population included: overdiagnosis due to increased sensitivity (i.e., Clostridium difficile), decreased yield of tests for respiratory pathogens, and lack of identification of important pathogens in this population such as, Aspergillus species. CONCLUSIONS: Although there is a scarcity of studies involving SOT patients, current available data suggests that the use of RDTs helps improve patient outcomes and minimizes inappropriate antimicrobial use when coupled with proactive ASPs. Future studies should focus on clinical outcomes in SOT patients specifically, as well as how to optimize the use of RDTs in conjunction with traditional microbiology methods.

Antifungal stewardship in solid-organ transplantation: What is needed?

BACKGROUND: Antifungal stewardship (AFS) lags behind antimicrobial stewardship (AMS) in terms of implementation, evidence base, and workforce experience. Solid-organ transplantation (SOT) carries a significant risk of invasive fungal infection, with high associated mortality, and is therefore associated with significant opportunities to optimize antifungal use. METHODS: A literature search for the terms "antifungal stewardship" and "solid-organ transplant" revealed a small evidence base to support AFS programs in this patient group. RESULTS: There is significant overlap in the methodology used in AMS and AFS programs, with notable differences in diagnostics, which are discussed in detail. The primary AFS interventions tested in SOT recipients are implementation of clinical guidelines and care bundles, digital enablers of AFS, and post-prescription review/audit and feedback. CONCLUSION: There is an urgent need for further research to support effective AFS strategies in this highly susceptible population.