OPTN/SRTR 2021 Annual Data Report: Intestine.

There has been just over 30 years of experience in clinical intestine transplant. A rise in demand until 2007 with improving transplant outcomes preceded a subsequent fall in demand due, at least in part, to improvements in pretransplant care of patients with intestinal failure. Over the past 10 to 12 years, there has been no suggestion of an increase in demand and, particularly for adult transplant, there may be a continued trend toward fewer additions to the waiting list and fewer transplants, especially in those needing combined intestine-liver transplant. In addition, over the same period there has been no noticeable improvement in graft survival, with 1- and 5-year graft failure rates averaging 21.6% and 52.5%, respectively, for intestine-alone transplants and 28.6% and 47.2%, respectively, for combined intestine-liver allografts.

OPTN/SRTR 2021 Annual Data Report: Vascularized Composite Allograft.

Year 2020 marked the first OPTN/SRTR Annual Data Report that included a chapter on vascularized composite allograft (VCA), which encompassed reviews of data collected between 2014 (when VCA was included in the Final Rule) and 2020. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and trended downward in 2021. While data continue to be limited by sample size, trends continue to show a predominance in White, young/middle-aged, male recipients. Similar to the 2020 report, eight uterus and one non-uterus VCA graft failures were reported from 2014 through 2021. Critical to advancement of VCA transplantation will be the standardization of definitions, protocols, and outcome measures for the different VCA types. Like intestinal transplants, it is likely that VCA transplants will be concentrated and performed at referral transplant centers.

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.

Kidney transplant in Denmark.

Since the first kidney transplant was conducted in Denmark in 1964, almost 10,000 transplants have been performed. Graft survival has improved over the past two decades despite the increase in age and comorbidities in both donors and recipients, but organ shortage remains a challenge. The focus of this review is to describe the challenges in kidney transplant and highlight the progress achieved in solving these challenges.

Reconstrucción escrotal con colgajo pediculado del músculo gracilis bilateral e injerto de piel parcial / Scrotal reconstruction with bilateral gracilis muscle pedicled flap and split-thickness skin graft

Los defectos en la región escrotal son producidos en la mayoría de los casos por la gangrena de Fournier, y en ocasiones por traumatismo o patologías oncológicas. Estas heridas generan mucha dificultad para el desarrollo de una vida normal a los pacientes que lo padecen; por lo general producen dolor, los testículos quedan desprotegidos y la espermatogénesis puede verse alterada. Actualmente no existe un método estándar de reconstrucción escrotal, y las técnicas tradicionalmente utilizadas no ofrecen una cobertura funcional ni estética. Generalmente producen mucho abultamiento en la región genital, que puede dificultar el movimiento de las piernas y el uso de pantalones. En este trabajo se expone una opción quirúrgica para reconstruir el escroto, por medio del colgajo pediculado de músculo gracilis bilateral e injerto de piel parcial. Para tal efecto, se presenta un caso clínico de un paciente de 64 años con secuelas en la región perineal, posterior a una gangrena de Fournier. El paciente presentaba una pérdida total del escroto y exposición de ambos testículos. El método arriba mencionado es una opción válida para reconstruir el escroto y en este trabajo se describe la técnica empleada de forma detallada, donde se puede apreciar que presenta escasas complicaciones y es fácil de reproducir por un cirujano plástico entrenado.

Defects in the scrotal region are caused in most cases by Fournier's gangrene, and sometimes by trauma or oncological pathologies. These wounds generate difficulties for the development of a normal life; They usually produce pain; the testicles are unprotected and spermatogenesis can be altered. Currently there is no standard method of scrotal reconstruction, and the techniques traditionally used do not offer functional or aesthetic coverage. They generally produce a big bulge in the genital region, which can make it hard to move the legs and wear pants. A surgical option is exposed to reconstruct the scrotum, by means of the bilateral gracilis muscle pedicled flap and split-thickness skin graft. For this purpose, a clinical case of a 64-year-old patient with sequelae in the perineal region, after Fournier's gangrene, is presented. The patient presented a total loss of the scrotum and exposure of both testicles. The method mentioned above is a valid option to reconstruct the scrotum and the technique used is described in detail, where it can be seen that it is easy to reproduce by a trained plastic surgeon.

Beyond donation to organ utilization in the UK.

PURPOSE OF REVIEW: Optimizing deceased donor organ utilization is gaining recognition as a topical and important issue, both in the United Kingdom (UK) and globally. This review discusses pertinent issues in the field of organ utilization, with specific reference to UK data and recent developments within the UK. RECENT FINDINGS: A multifaceted approach is likely required in order to improve organ utilization. Having a solid evidence-base upon which transplant clinicians and patients on national waiting lists can base decisions regarding organ utilization is imperative in order to bridge gaps in knowledge regarding the optimal use of each donated organ. A better understanding of the risks and benefits of the uses of higher risk organs, along with innovations such as novel machine perfusion technologies, can help clinician decision-making and may ultimately reduce the unnecessary discard of precious deceased donor organs. SUMMARY: The issues facing the UK with regards to organ utilization are likely to be similar to those in many other developed countries. Discussions around these issues within organ donation and transplantation communities may help facilitate shared learning, lead to improvements in the usage of scarce deceased donor organs, and enable better outcomes for patients waiting for transplants.

Cobertura vacunal, creenciasy actitudes en niños y adolescentes trasplantados: una revisión sistemática de métodos mixtos / Vaccination coverage, beliefs, and attitudes in transplanted children and adolescents: a mixed-methods systematic review

Fundamentos: Las enfermedades infecciosas prevenibles mediante vacunación son una causa de morbilidad y mortalidaden niños trasplantados. El objetivo principal de este estudio fue sintetizar la evidencia disponible de la cobertura vacunal en niñosy adolescentes candidatos o receptores de trasplante y analizar las creencias, actitudes y experiencias acerca de la vacunación. Métodos: Se realizó una revisión sistemática de métodos mixtos (registro Open Science Framework:https://osf.io/auqn3/). Se lleva-ron a cabo búsquedas enPubMed/MEDLINE, EMBASE, IBECS yLILACS (desde enero de 2000 hasta agosto de 2021) y en literatura gris. Losestudios cuantitativos y cualitativos informaron sobre cobertura, creencias, actitudes y/o experiencias con respecto a cualquier vacunarecomendada en niños candidatos o receptores de trasplante de órganos sólidos y/o progenitores hematopoyéticos. Se evaluó la calidadmetodológica mediante la herramienta MMAT (Mixed Methods Appraisal Tool). Se llevó a cabo una síntesis narrativa de los estudios. Resultados: Se incluyeron treinta y dos estudios disponibles en treinta y cinco publicaciones. Las intervenciones más estu-diadas fueron las vacunas frente a sarampión (n=21; 66%) y hepatitis B (n=20; 62%). Las tasas de inmunización mostraron una altavariabilidad para las vacunas más representadas (concretamente, 2%-100% en sarampión, 0,4%-100% en hepatitis B, difteria-téta-nos-tosferina y rubeola), con coberturas inferiores al 90% en al menos el 70% de los estudios. Los valores más bajos se registraronen situación postrasplante y trasplante de progenitores hematopoyéticos. Sólo se identificó un estudio cualitativo que incluyó infor-mación sobre creencias y/o actitudes, aunque nueve estudios cuantitativos exploraron aspectos cognitivos. Conclusiones: Esta revisión muestra una elevada variabilidad en la cobertura vacunal de niños candidatos o receptores detrasplante, con cifras generalmente inferiores a las...(AU)

Background: Vaccine-preventable infectious diseases are a cause of morbidity and mortality in transplanted children. Themain objective of this study was to synthesize the available evidence of vaccination coverage in children and adolescents who arecandidates or transplant recipients and to analyze beliefs, attitudes, and experiences about vaccination. Methods: A mixed-methods systematic review was performed (Open Science Framework registration:https://osf.io/auqn3/). Sear-ches were conducted in PubMed/MEDLINE, EMBASE, IBECS and LILACS (from January 2000 to August 2021) and in gray literature. Quan-titative and qualitative studies reported information on coverage, beliefs, attitudes and/or experiences about recommended vaccines inchildren who are candidates or recipients of solid organ or hematopoietic progenitor transplantation. Quality assessment was undertakenusing Mixed Methods Appraisal Tool (MMAT). A narrative synthesis of the studies was carried out. Results: A total of thirty-two studies in thirty-five publications were included. The most studied interventions were vaccinesagainst measles (n=21; 66%) and hepatitis B (n=20; 62%). Vaccination rates showed a high variability for the most representedvaccines (specifically, 2%-100% for measles, 0.4%-100% for hepatitis B, diphtheria-tetanus-pertussis and rubella), with coverageslower than 90% in at least 70% of the studies. The lowest rates were reported in post-transplantation and hematopoietic stem celltransplantation. Only one qualitative study was identified reporting information on beliefs and/or attitudes, although nine quantitativestudies explored cognitive aspects. Conclusions: This review shows a high variability in vaccination coverage in children and adolescents who are transplantcandidates or recipients, with rates lower than those recommended. Further studies would be needed to identify beliefs and attitudesabout immunization in this context.(AU)

Cold Storage Followed by Transplantation Induces Interferon-Gamma and STAT-1 in Kidney Grafts.

Cold storage (CS)-mediated inflammation, a reality of donor kidney processing and transplantation, can contribute to organ graft failure. However, the mechanisms by which this inflammation is perpetuated during and after CS remain unclear. Here, we examined the immunoregulatory roles of signal transducer and activator of transcription (STAT) family proteins, most notably STAT1 and STAT3, with our in vivo model of renal CS and transplant. Donor rat kidneys were exposed to 4 h or 18 h of CS, which was then followed by transplantation (CS + transplant). STAT total protein level and activity (phosphorylation) were evaluated via Western blot analysis and mRNA expression was tabulated using quantitative RT-PCR after organ harvest on day 1 or day 9 post-surgery. In vivo assays were further corroborated via similar analyses featuring in vitro models, specifically proximal tubular cells (human and rat) as well as macrophage cells (Raw 264.7). Strikingly, gene expression of IFN-γ (a pro-inflammatory cytokine inducer of STAT) and STAT1 were markedly increased after CS + transplant. STAT3 dephosphorylation was additionally observed after CS, a result suggestive of dysregulation of anti-inflammatory signaling as phosphorylated STAT3 acts as a transcription factor in the nucleus to increase the expression of anti-inflammatory signaling molecules. In vitro, IFN-γ gene expression as well as amplification of downstream STAT1 and inducible nitric oxide synthase (iNOS; a hallmark of ischemia reperfusion injury) was remarkably increased after CS + rewarming. Collectively, these results demonstrate that aberrant induction of STAT1 is sustained in vivo post-CS exposure and post-transplant. Thus, Jak/STAT signaling may be a viable therapeutic target during CS to mitigate poor graft outcomes when transplanting kidneys from deceased donors.

Xenotransplantation: A historical-ethical account of viewpoints.

Formal clinical trials of pig-to-human organ transplant-known asxenotransplantation-may begin this decade, with the first trials likely to consist of either adult renal transplants or pediatric cardiac transplant patients. Xenotransplantation as a systematic scientific study only reaches back to the latter half of the 20th century, with episodic xenotransplantation events occurring prior to that. As the science of xenotransplantation has progressed in the 20th and 21st centuries, the public's knowledge of the potential therapy has also increased. With this, there have been shifting ethical stances toward xenotransplantation in key areas, such as religious and public viewpoints towards xenotransplantation, animal rights, and public health concerns. This review provides a historical-ethical account of xenotransplantation and details if or how viewpoints have shifted over time.

Haploidentical Transplant Achieves Long-Term Remission in Relapsed Refractory Leukemia With Fludarabine-Induced Neurotoxicity Complication.

Hematopoietic stem cell transplant is potentially curative for relapsed/refractory leukemia. However, neurotoxicity is common and has been reported in 11% to 59% of children following hematopoietic stem cell transplant. Most pediatric studies of the neurological effects of hematopoietic stem cell transplant have focused on acute neurotoxicity. Limited information is available for long-term neurotoxicity, particularly those cases that are severe and permanent and caused by conditioning chemotherapy. Here, we report 2 cases of relapsed acute lymphoblastic leukemia that achieved long-term remission by haploidentical hematopoietic stem cell transplant but remained complicated with severe and persistent fludarabine-induced neurotoxicity.

Renal transplantation: the last iteration of the rest of the world.

PURPOSE OF REVIEW: Renal transplantation systems across the world aim to achieve an optimal balance between fair access to deceased donor kidney transplants (equity) and efficient use of organs (utility). Kidney allocation systems are measured across a host of metrics, and there is no single agreed upon definition of success, which looks different for each system depending on the desired balance between equity and utility. This article evaluates the United States renal transplantation system's efforts to balance equity and utility while drawing comparisons to other national systems. RECENT FINDINGS: The United States renal transplantation system is expected to undergo major changes with the transition to a continuous distribution framework. The continuous distribution framework removes geographic boundaries and takes a flexible and transparent approach to balancing equity and utility. The framework leverages transplant professionals and community members input with mathematical optimization strategies to inform weighting of patient factors to allocate deceased donor kidneys. SUMMARY: The United States' proposed continuous allocation framework lays the groundwork for a system allowing transparent balancing of equity and utility. This system approach addresses issues common to those in many other countries.

Pregnancy in end-stage kidney disease: Great news that needs to be handled carefully.

Compared to women with normal kidney function, women with end-stage kidney disease (ESKD) are much less likely to become pregnant, but more likely to have a complicated pregnancy. While renal transplantation remains the best option for women who desire to have a child, pregnancy on dialysis should be considered an option for those who may not receive a transplant during their reproductive years. Many physicians do not encounter a pregnant patient with ESKD during their nephrology training, and may not feel prepared to provide care for such patients in a busy practice. In this paper, we briefly provide an overview of the most significant practical points related to management of a pregnant patient with ESKD through a real-life case with twin pregnancy. The two key elements in management of these patients would be an intensified hemodialysis regimen and a multidisciplinary team that can provide frequent, regular, and multifaceted assessments.

The Use of the Implantable Doppler Probe as a Blood Flow Monitoring Device in Clinical Settings: A Narrative Review of the Evidence.

OBJECTIVES: In the past decade, the implantable Doppler probe has been studied widely as a blood flow-monitoring device in reconstructive and transplant surgical specialities. Its utility as an effective postoperative monitoring technique is still debatable, with no clear guidelines in clinical practice. Here, we mapped the current evidence on the usefulness of the implantable Doppler probe as a blood flow-monitoring device. The objective was to present an up-to-date assessment of the benefits and limitations of using implantable Doppler probes in clinical and experimental clinical settings. MATERIALS AND METHODS: We conducted a literature search using the Cochrane Library and Healthcare Databases Advanced Search and using implantable Doppler probe, transplant, graft, and flap as key words. The search yielded 184 studies, with 73 studies included after exclusions. We evaluated, synthesized, and summarized the evidence from the studies in tabular form. RESULTS: There is clinical equipoise regarding the effectiveness of implantable Doppler probe as a flow sensing technique. The main reason is the lack of information and gaps in the evidence regarding the benefits and limitations of using implantable Doppler probes in clinical practice. CONCLUSIONS: The implantable Doppler probe has the potentialto be used as an adjunctpostoperativeblood flow-monitoring device. However, keeping in view of technical limitations, its signals should be interpreted alongside traditional clinical assessment techniques to determine the patency of microvascular anastomosis. Although evidence in this review will inform clinical practice in transplant and reconstructive surgical specialties, a prospective randomized controlled study with a larger patient cohort is required to evaluate the effectiveness of this probe in clinical settings.

Translational Orthotopic Models of Glioblastoma Multiforme.

Genetically engineered mouse (GEM) models for human glioblastoma multiforme (GBM) are critical to understanding the development and progression of brain tumors. Unlike xenograft tumors, in GEMs, tumors arise in the native microenvironment in an immunocompetent mouse. However, the use of GBM GEMs in preclinical treatment studies is challenging due to long tumor latencies, heterogeneity in neoplasm frequency, and the timing of advanced grade tumor development. Mice induced via intracranial orthotopic injection are more tractable for preclinical studies, and retain features of the GEM tumors. We generated an orthotopic brain tumor model derived from a GEM model with Rb, Kras, and p53 aberrations (TRP), which develops GBM tumors displaying linear foci of necrosis by neoplastic cells, and dense vascularization analogous to human GBM. Cells derived from GEM GBM tumors are injected intracranially into wild-type, strain-matched recipient mice and reproduce grade IV tumors, therefore bypassing the long tumor latency period in GEM mice and allowing for the creation of large and reproducible cohorts for preclinical studies. The highly proliferative, invasive, and vascular features of the TRP GEM model for GBM are recapitulated in the orthotopic tumors, and histopathology markers reflect human GBM subgroups. Tumor growth is monitored by serial MRI scans. Due to the invasive nature of the intracranial tumors in immunocompetent models, carefully following the injection procedure outlined here is essential to prevent extracranial tumor growth.

Newspaper Campaign to Promote Deceased Organ Donation: Who Can Appeal to the General Japanese Population?

BACKGROUND: Various interventions are reportedly effective in promoting organ donor registration. However, the identity of those who best serve as presenters to appeal to the general public is not known. METHODS: A campaign for organ donor registration was conducted through a local newspaper advertisement in Japan. The advertisement appeared in 439,733 copies of the newspaper on January 9, 2021. In addition to the main message, 6 different presenters with photos of their faces and quick response codes were listed in the advertisement, namely a urologist, transplant physician, nephrologist, dialysis physician, ophthalmologist, and kidney transplant recipient who was a nephrologist himself (ie, a recipient and nephrologist). Newspaper readers watched each video about deceased organ donation via the quick response codes, and the number of video views acquired 30 days after the appearance was the main outcome, which was assessed using YouTube analytics. The proportions (95% CI) of people who watched each video among 439,733 newspaper readers were compared among the 6 presenters. RESULTS: The analyzed videos were viewed 262 times. The video produced by the recipient and nephrologist had the highest number of views among the 6 presenters (proportion: 0.019% [95% CI, 0.015-0.023]), followed by the one produced by the dialysis physician (0.011% [95% CI, 0.008-0.014]), the nephrologist (0.010% [95% CI, 0.007-0.014]), the urologist (0.008% [95% CI, 0.006-0.012]), the transplant physician (0.006% [95% CI, 0.004-0.009]), and the ophthalmologist (0.005% [95% CI, 0.004-0.008]). CONCLUSIONS: The appeal by the recipient and the nephrologist reached the highest proportion of people who watched the video about deceased organ donation in Japan.