New solutions in transplantology and graft acquisition.

In view of rapid advancements in the field of transplantology, emerging solutions in tissue procurement for transplantation became a crucial area of research. Tissue transplantation plays a notable role in improving the quality of life for patients afflicted with various ailments, and the increasing number of transplants necessitates the exploration of innovative procurement methods. This study examines a new direction in transplantology, placing focus on innovative approaches to tissue procurement and discussing the commonly used method of "ex mortuo," i.e., retrieving organs from deceased donors. Given the growing demand for organs, the paper discusses the innovative approach slowly emerging as 3D bioprinting. The paper discusses the key challenges associated with the use of this method in transplantology, including issues of biocompatibility, vascularization, and integration with the immune system. The paper also discusses the latest scientific achievements in the field, such as the first transplants of bioprinted organs, demonstrating the practical application of this technology in medicine. It is also the analysis of the ethical, social, and legal aspects related to these new solutions. The article provides a comprehensive overview of the latest trends in transplantology and presents a holistic view of the current state of knowledge and prospects for development in this pivotal area of medicine.

Clinical Deployment of Machine Learning Tools in Transplant Medicine: What Does the Future Hold?

Medical applications of machine learning (ML) have shown promise in analyzing patient data to support clinical decision-making and provide patient-specific outcomes. In transplantation, several applications of ML exist which include pretransplant: patient prioritization, donor-recipient matching, organ allocation, and posttransplant outcomes. Numerous studies have shown the development and utility of ML models, which have the potential to augment transplant medicine. Despite increasing efforts to develop robust ML models for clinical use, very few of these tools are deployed in the healthcare setting. Here, we summarize the current applications of ML in transplant and discuss a potential clinical deployment framework using examples in organ transplantation. We identified that creating an interdisciplinary team, curating a reliable dataset, addressing the barriers to implementation, and understanding current clinical evaluation models could help in deploying ML models into the transplant clinic setting.

Alternative Therapies in Transplantology as a Promising Perspective in Medicine.

Despite continuous and rapid progress in the transplantation of cells, tissues, and organs, many patients die before receiving them. This is because of an insufficient number of donors, which leads to a significant disproportion between the need for donors and their availability. This review aims to present the possibilities offered by alternative therapies. We use the term "functional transplantology" to describe such alternative methods of transplantation that could help change the current state of transplantation medicine. Its purpose is not to replace a defective or removed organ with another but to replace its functions using complementary biological, mechanical, or biomechanical structures or devices. Implementation of many innovative solutions shown in the work for clinical applications is already a fact. In the case of others, it should be considered a future vision. We hope that the role of a defective or damaged tissue or a group of tissues will be taken over by different structures that are functionally complementary with the organ being substituted. Undoubtedly, developing the described methods based on functional transplantology will change the face of transplantation medicine. Thus, we show current trends and new directions of thinking and actions in transplantation medicine that combine technology and transplantology. The review considers the latest technologies, including 3D bioprinting, nanotechnology, cell encapsulation, and organoids. We discuss not only the advantages of new approaches but also the limitations and challenges that must be overcome to achieve significant progress in transplantation. That is the only option to provide a safe and efficient way of improving the quality of life of many patients.

Organ Donation in Syria.

The first living donor kidney transplant in Syria was performed 44 years ago; by the end of 2022, 6265 renal transplants had been performed in Syria. Kidney, bone marrow, cornea, and stem cells are the only organs or tissues that can be transplanted in Syria. Although 3 heart transplants from deceased donors were performed in the late 1980s, cardiac transplant activities have since discontinued. In 2003, national Syrian legislation was enacted authorizing the use of organs from living unrelated and deceased donors. This important law was preceded by another big stride: the acceptance by the higher Islamic religious authorities in Syria in 2001 of the principle of procurement of organs from deceased donors, provided that consent is given by a first- or second-degree relative. After the law was enacted, kidney transplant rates increased from 7 per million population in 2002 to 17 per million population in 2007. Kidney transplants performed abroad for Syrian patients declined from 25% in 2002 to <2% in 2007. Rates plateaued through 2010, before the political crisis started in 2011. Forty-four years after the first successful kidney transplant in Syria, patients needing an organ transplant rely on living donors only. Moreover, 20 years after the law authorizing use of organs from deceased donors, a program is still not in place in Syria. The war, limited resources, and lack of public awareness about the importance of organ donation and transplant appear to be factors inhibiting initiation of a deceased donor program in Syria. A concerted and ongoing education campaign is needed to increase awareness of organ donation, change negative public attitudes, and gain societal acceptance. Every effort must be made to initiate a deceased donor program to lessen the burden on living donors and to enable national self-sufficiency in organs for transplant.

Abdominal Transplant Surgeons: The Lack of Female Surgeons and People From Underrepresented Racial and Ethnic Minority Groups in Academic and Clinical Leadership.

OBJECTIVES: The demographic disparities among surgeons in academic leadership positions is well documented. We aimed to characterize the present demographic details of abdominal transplant surgeons who have achieved academic and clinical leadership positions. MATERIALS AND METHODS: We reviewed the 2022-2023 American Society of Transplant Surgeons membership registry to identify 1007 active abdominal transplant surgeons. Demographic details (academic and clinical titles) were collected and analyzed using the chi-square test, the Fisher exact test, and t tests. Multinomial logistic regressions were conducted. RESULTS: Female surgeons (P < .001) and surgeons from racial-ethnic minorities (P = .027) were more likely to be assistants or associates rather than full professors. White male surgeons were more likely to be full professors than were White female (P < .001), Asian female (P = .008), and Asian male surgeons (P = .005). There were no Black female surgeons who were full professors. The frequency of full professorship increased with surgeon age (P < .001). Male surgeons were more likely to hold no academic titles (P < .001). Female surgeons were less likely to be chief of transplant(P = .025), chief of livertransplant (P = .001), chief of pancreas transplant (P = .037), or chair of surgery (P = .087, significance at 10%). Chief of kidney transplant was the most common clinical position held by a surgeon from a racial or ethnic minority group. Female surgeons were more likely to hold no clinical titles (P = .001). CONCLUSIONS: The underrepresentation of women and people from racial and ethnic minority groups in academic and clinical leadership positions in the field of abdominal transplant surgery remains evident. White male physicians are more likely to obtain full professorship, and they comprise most of the clinical leadership positions overall. A continued push for representative leadership is needed.

Bibliometric analysis and global trends in uterus transplantation.

AIM: The purpose of this study was to characterize publication patterns, academic influence, research trends, and the recent developments in uterus transplantation (UTx) across the globe. METHODS: The Web of Science Core Collection database was searched for documents published from the time the database began to include relevant articles to 15 December 2023. With the use of VOSviewer, Citespace, BICOMB, and Incites, a cross-sectional bibliometric analysis was conducted to extract or calculate the evaluative indexes. Publications were categorized by country, institution, author, journal, highly cited papers, and keywords. The variables were compared in terms of publication and academic influence, which further included citation count, citation impact, Hirsh index, journal impact factor, total link strength, collaboration metrics, and impact relative to the world. RESULTS: A total of 581 papers concerning UTx were initially identified after retrieval, and 425 documents were included. Of the 41 countries participating in relevant studies, the USA and Sweden were in leading positions in terms of publications, citations, and academic influence. The most versatile institution was the University of Gothenburg, followed by Baylor University. The most productive scholars and journals were Brännström M. and Fertility and Sterility , respectively. Five groups of cutting-edge keywords were identified: venous drainage, donors and donation, women, fertility preservation, and fertility. Topics about surgery, first live birth, risk, and in vitro fertilization remain hot in this field. CONCLUSIONS: UTx is anticipated to enter a golden era in the coming years. This study provides some guidance concerning the authors involved in promoting UTx research, the current development of UTx, and journals to submit their innovative research. This also helps to reach a comprehensive insight and prospect in the near future. In order to establish recognized standards and benefit more patients who are disturbed by uterine infertility, large-scale and well-designed clinical trials are required.

Organ Donation from Patients Receiving Extracorporeal Membrane Oxygenation: A Systematic Review.

OBJECTIVE: The mismatch between the demand for and supply of organs for transplantation is steadily growing. Various strategies have been incorporated to improve the availability of organs, including organ use from patients receiving extracorporeal membrane oxygenation (ECMO) at the time of death. However, there is no systematic evidence of the outcome of grafts from these donors. DESIGN: Systematic literature review (Scopus and PubMed, up to October 11, 2023). SETTING: All study designs. PARTICIPANTS: Organ recipients from patients on ECMO at the time of death. INTERVENTION: Outcome of organ donation from ECMO donors. MEASUREMENTS AND MAIN RESULTS: The search yielded 1,692 publications, with 20 studies ultimately included, comprising 147 donors and 360 organ donations. The most frequently donated organs were kidneys (68%, 244/360), followed by liver (24%, 85/360). In total, 98% (292/299) of recipients survived with a preserved graft function (92%, 319/347) until follow-up within a variable period of up to 3 years. CONCLUSION: Organ transplantation from donors supported with ECMO at the time of death shows high graft and recipient survival. ECMO could be a suitable approach for expanding the donor pool, helping to alleviate the worldwide organ shortage.

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.

Viral Enteritis in Solid-Organ Transplantation.

Solid organ transplant recipients are at increased risk for infections due to chronic immunosuppression. Diarrhea is a commonly encountered problem post transplantation, with infectious causes of diarrhea being a frequent complication. Viral infections/enteritides in solid organ transplant recipients often result from frequently encountered pathogens in this population such as cytomegalovirus, adenovirus, and norovirus. However, several emerging viral pathogens are increasingly being recognized as more sensitive diagnostic techniques become available. Treatment is often limited to supportive care and reduction in immunosuppression, though antiviral therapies mayplay a role in the treatment in certain diseases. Viral enteritis is an important entity that contributes to morbidity and mortality in transplant recipients.

Cellular Therapies in Solid Organ Allotransplantation: Promise and Pitfalls.

Donor specific transfusions have been the basis of tolerance inducing protocols since Peter Medawar showed that it was experimentally feasible in the 1950s. Though trials of cellular therapies have become increasingly common in solid organ transplantation, they have not become standard practice. Additionally, whereas some protocols have focused on cellular therapies as a method for donor antigen delivery-thought to promote tolerance in and of itself in the correct immunologic context-other approaches have alternatively focused on the intrinsic immunosuppressive properties of the certain cell types with less emphasis on their origin, including mesenchymal stem cells, regulatory T cells, and regulatory dendritic cells. Regardless of intent, all cellular therapies must contend with the potential that introducing donor antigen in a new context will lead to sensitization. In this review, we focus on the variety of cellular therapies that have been applied in human trials and non-human primate models, describe their efficacy, highlight data regarding their potential for sensitization, and discuss opportunities for cellular therapies within our current understanding of the immune landscape.

Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs.

Immunosuppressive drugs used in the transplantation period are generally defined as induction and maintenance therapy. The use of immunosuppressants, which are particularly useful and have fewer side effects, decreased both mortality and morbidity. Many drugs such as steroids, calcineurin inhibitors (cyclosporine-A, tacrolimus), antimetabolites (mycophenolate mofetil, azathioprine), and mTOR inhibitors (sirolimus, everolimus) are used as immunosuppressive agents. Although immunosuppressant drugs cause many side effects such as hypertension, infection, and hyperlipidemia, they are the agents that should be used to prevent organ rejection. This shows the importance of individualized drug use. The optimal immunosuppressive therapy post-transplant is not established. Therefore, discovering less toxic but more potent new agents is of great importance, and new experimental and clinical studies are needed in this regard.Our review discussed the mechanism of immunosuppressants, new agents' discovery, and current therapeutic protocols in the transplantation.

Use of cryopreserved ovarian tissue in the Danish fertility preservation cohort.

OBJECTIVE: To evaluate the use of cryopreserved ovarian tissue in the Danish fertility preservation cohort. DESIGN: Retrospective cohort study. SETTING: University hospitals and fertility clinics. PATIENT(S): Ovarian tissue cryopreservation (OTC) was performed for 1,186 Danish girls and women from 1999-2020, of whom 117 subsequently underwent ovarian tissue transplantation (OTT). Subgroup 1 included 759 patients with a follow-up period of >5 years. Out of these, OTT rates were further analyzed for those patients who were alive and aged >24 years in July 2020 (subgroup 2; n = 554). INTERVENTION(S): OTC and OTT. MAIN OUTCOME MEASURE(S): OTT, death, donation of tissue. RESULT(S): In subgroup 1, 14% of the patients had undergone OTT, 18% had died, 9% had donated their tissue for research, and 59% still had their tissue stored. In subgroup 2, 19% had undergone OTT and for most diagnoses the OTT rates ranged from 15% to 22% with benign hematologic diseases having the highest OTT rate (35%). On the basis of the entire cohort, stratified age analysis indicated that women aged ≥30 years at OTC were more likely to return for OTT than women aged 18-29 years at OTC; mean storage times were 3.7 and 3.6 years, respectively. Only 4% of the girls aged <18 years at OTC had undergone OTT. CONCLUSION(S): The OTT rates depended on the diagnosis, age at OTC, and follow-up time. Specific criteria are needed for reporting and comparing OTT rates. Six out of 10 patients still had their cryopreserved tissue stored and longer follow-up is needed, especially for younger girls.

Donor-derived Cell-free DNA in Solid-organ Transplant Diagnostics: Indications, Limitations, and Future Directions.

The last few years have seen an explosion in clinical research focusing on the use of donor-derived cell-free DNA (dd-cfDNA) in solid-organ transplants (SOT). Although most of the literature published so far focuses on kidney transplants, there are several recent as well as ongoing research studies on heart, lung, pancreas, and liver transplants. Though initially studied as a noninvasive means of identifying subclinical or acute rejection in SOT, it is rapidly becoming clear that instead of being a specific marker for allograft rejection, dd-cfDNA is more appropriately described as a marker of severe injury, although the most common cause of this injury is allograft rejection. Multiple studies in kidney transplants have shown that although sensitivity for the diagnosis of antibody-mediated rejection is excellent, it is less so for T-cell-mediated rejection. It is possible that combining dd-cfDNA with other novel urine- or blood-based biomarkers may increase the sensitivity for the diagnosis of rejection. Irrespective of the cause, though, elevated dd-cfDNA seems to portend adverse allograft prognosis and formation of de novo donor-specific antibody. Although current data do not lend themselves to a clear conclusion, ongoing studies may reveal the utility of serial surveillance for the management of SOT as following levels of dd-cfDNA over time may provide windows of opportunity to intervene early and before irreversible allograft injury. Finally, cost-effectiveness studies will be needed to guide the ideal incorporation of dd-cfDNA into routine clinical practice.

Impact of COVID-19 in solid organ transplant recipients.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exploded onto the world stage in early 2020. The impact on solid organ transplantation (SOT) has been profound affecting potential donors, candidates, and recipients. Importantly, decreased donations and the pressure of limited resources placed on health care by the pandemic also disrupted transplant systems. We address the impact of COVID-19 on organ transplantation globally and review current understanding of the epidemiology, outcomes, diagnosis, and treatment of COVID-19 in SOT recipients.

Chimerism as the basis for organ repair.

Organ and tissue repair are complex processes involving signaling molecules, growth factors, and cell cycle regulators that act in concert to promote cell division and differentiation at sites of injury. In embryonic development, progenitor fetal cells are actively involved in reparative mechanisms and display a biphasic interaction with the mother; and there is constant trafficking of fetal cells into maternal circulation and vice versa. This phenomenon of fetal microchimerism may have significant impact considering the primitive, multilineage nature of these cells. In published work, we have reported that fetal-derived placental cells expressing the homeodomain protein CDX2 retain all "stem" functional proteins of embryonic stem cells yet are endowed with additional functions in areas of growth, survival, homing, and immune modulation. These cells exhibit multipotency in vitro and in vivo, giving rise to spontaneously beating cardiomyocytes and vascular cells. In mouse models, CDX2 cells from female placentas can be administered intravenously to male mice subjected to myocardial infarction with subsequent homing of the CDX2 cells to infarcted areas and evidence of cellular regeneration with enhanced cardiac function. Elucidating the role of microchimeric fetal-derived placental cells may have broader scientific potential, as one can envision allogeneic cell therapy strategies targeted at tissue regeneration for a variety of organ systems.

Declínio nas doações e transplantes de órgãos no Ceará durante a pandemia da COVID-19: estudo descritivo, abril a junho de 2020 / Disminución de donaciones y trasplantes de órganos en Ceará durante la pandemia COVID-19: un estudio descriptivo, abril - junio de 2020 / Fall in organ donations and transplants in Ceará in the COVID-19 pandemic: a descriptive study, April - June 2020

Objetivo Descrever as doações e os transplantes de órgãos no Ceará, Brasil, após a declaração da pandemia da COVID-19. Métodos Estudo descritivo, com dados da Associação Brasileira de Transplantes de Órgãos. O número de doadores e transplantes do período de abril a junho de 2020 foi comparado ao mesmo período de 2019 e ao primeiro trimestre de 2020. Resultados No primeiro semestre de 2020, o estado registrou 72 doadores efetivos. Destes, 17 (23,6%) no segundo trimestre. Dos 352 transplantes do primeiro semestre de 2020, 37 (10,7%) foram realizados no segundo trimestre. Em comparação ao período de abril a junho de 2019, houve redução de 67,9% e 89,3% no número de doadores e transplantes, respectivamente, no mesmo período de 2020. Conclusão Os números de doadores e transplantes do Ceará apresentaram importante declínio nos três meses seguintes ao decreto da pandemia da COVID-19, especialmente os das modalidades de rim, coração e córneas.

Objetivo Describir las donaciones y trasplantes de órganos en Ceará, Brasil, después de la declaración de la pandemia COVID-19. Métodos estudio descriptivo con datos de la Asociación Brasileña de Trasplantes de Órganos. Se comparó el número de donantes y trasplantes de abril a junio de 2020 con el mismo período de 2019 y el primer trimestre de 2020. Resultados El primer semestre de 2020, Ceará registró 72 donantes efectivos. De estos, 17 (23,6%) en el segundo trimestre. De 352 trasplantes realizados en el primer semestre de 2020, 37 (10.7%) fueron realizados en el segundo trimestre. En comparación al período de abril a junio de 2019, hubo reducción de 67,9% y 89,3% en el número de donantes y trasplantes, respectivamente, en el mismo período de 2020. Conclusión El número de donantes y trasplantes en Ceará mostró importante disminución en los tres meses siguientes al decreto pandémico COVID-19, especialmente las modalidades renal, cardíaca y córneas.

Objective To describe organ donations and transplants in Ceará state, Brazil, following the declaration of the COVID-19 pandemic. Methods This was a descriptive study using data from the Brazilian Organ Transplantation Association. The number of donors and transplants from April to June 2020 was compared to the same period in 2019 and to the first quarter of 2020. Results In the first half of 2020, the state registered 72 effective donors, just 17 (23.6%) of whom related to the second quarter. Of the 352 transplants in the first half of 2020, 37 (10.7%) were performed in the second quarter. Compared with the period from April to June 2019, there was a reduction of 67.9% and 89.3% in the number of donors and transplants, respectively, in the same period of 2020. Conclusion The number of donors and transplants in Ceará showed an important fall in the three months following the declaration of the COVID-19 pandemic, especially for kidney, heart and cornea transplants.