Acute Liver Failure in a Child With Adenovirus Detected by PCR in the Explanted Liver.

As of June 15, 2022, the Centers for Disease Control and Prevention has reported 296 pediatric patients under investigation for hepatitis of unknown etiology in the United States; the World Health Organization has reported 650 probable cases worldwide. One of the leading hypotheses for this cluster of cases is adenovirus, a virus that commonly causes respiratory or gastrointestinal symptoms in healthy children but rarely causes severe hepatitis or acute liver failure in immunocompetent children. The other leading hypothesis is that prior infection with SARS-CoV-2 may predispose children to developing liver injury from a normally innocuous agent. We describe a case of a previously healthy child presenting with acute liver failure who had detectable adenovirus DNA in his stool, whole blood, and in liver explant tissue, suggesting adenovirus as the likely etiology for the liver failure. He had no evidence of prior or current SARS-CoV-2 infection, nor had he received COVID vaccination, suggesting that SARS-CoV-2 did not play a role. Additionally, we report on the ability to provide rapid evaluation of a living donor within 72 hours and successfully perform a lifesaving, left-lobe, living donor liver transplant.

Trends in organ donation and transplantation over the past eighteen years in Iran.

BACKGROUND: This article will review the trends in organ donation over the past 18 years in Iran. MATERIAL AND METHODS: All donation and transplantation statistics were extracted by reviewing the Organ Procurement and Transplantation database of the Ministry of Health of Iran from 2002 to 2019. RESULTS: Iran's national deceased donation rate from 2002 to 2019 increased 19.06-fold from .75 to 14.3 per million population (PMP). After the beginning of the COVID-19 pandemic, the rate of organ donation in Iran decreased significantly. Although 1 year after the onset of the pandemic, due to the widespread adoption of COVID19 vaccination, the rate of organ donation began to increase again, this system is still under performing. During the years under examination, the rate of deceased kidney donation increased significantly compared to living kidney donation and reached up to 2001 kidney transplantations in 2021. From 2002 to 2019, the rate of liver transplants increased to 12.8. Likewise, the rate of heart transplants increased 8.4-fold, from 15 to 126 cases during the same time. CONCLUSSION: Although a personal choice, the process of organ donation involves medical, legal, ethical, organizational, and social aspects. The trend in increasing donation rates over the past years can be attributed to multiple influences, which include rigorous team efforts in the organ donation and transplantation systems, in addition to creating a donation culture and promoting donation through media platforms. Moreover, we can say that the rising rates of deceased donor transplantation also can drive down rates of commercial living donor transplantation.

Meeting Report: Third International Congress of the International Society of Uterus Transplantation, Tübingen.

Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. The International Society of Uterus Transplantation (ISUTx) was formally founded in 2017 and joined the Transplantation Society as a formal section in 2021. The Third International Congress of the ISUTx was held in Tübingen, Germany, in October 2021, as a hybrid meeting, attended virtually by about 450 delegates and in person by 35 delegates. This report summarizes the Tübingen meeting and complementary topics of relevance presented at the Second ISUTx state-of-the-art webinar meeting, held in Prague, in October 2020. Main topics covered included surgical considerations, including dissection of veins in living donors and the pros and cons of minimally invasive surgery; managing immune risks; UTx during the COVID-19 pandemic; lessons learnt in the areas of imaging and cytomegalovirus infection; long-term psychological outcomes; opportunities to increase organ availability; and new horizons in UTx, including potential reuse of transplants and the utilization of robotic approaches. Implementation of an International UTx Registry was discussed and considered crucial to assure quality, safety, and further progress in UTx. Attempts made thus far have been promising.

The effect of the COVID-19 pandemic on deceased and living organ donors in the United States of America.

A life-saving treatment, solid organ transplantation (SOT) has transformed the survival and quality of life of patients with end-organ dysfunction. The coronavirus disease (COVID-19) pandemic has impacted the practice of deceased and living donations worldwide by various resource shifting, including healthcare personnel and equipment such as ventilators and bed space. Our work explores the COVID-19 pandemic and global transplant data to create a statistical model for deducing the impact of COVID-19 on living donor and deceased donor transplants in the United States of America (USA). In severely impacted regions, transplant centers need to carefully balance the risks and benefits of performing a transplant during the COVID-19 pandemic. In our statistical model, the COVID cases are used as an explanatory variable (input) to living or deceased donor transplants (output). The model is shown to be statistically accurate for both estimation of the correlation structure, and prediction of future donors. The provided predictions are to be taken as probabilistic assertions, so that for each instant where the prediction is calculated, a statistical measure of accuracy (confidence interval) is provided. The method is tested on both low and high frequency data, that notoriously exhibit a different behavior.

Outcomes of Living Donor Kidney Transplant After SARS-CoV-2 Infection in Both the Donor and the Recipient: A Multicenter Study.

OBJECTIVES: Evidence on living donor kidney transplant procedures when both the donor and recipient have had a history of COVID-19 infection is scarce. MATERIALS AND METHODS: We retrospectively explored the protocol, outcomes, and follow-up of 64 donors and recipients of living donor kidney transplant who had recovered from COVID-19. This was a multicenter (n = 12) study from India that included transplants between October 29, 2020, and December 1, 2021. Induction and immunosuppression regimens forthose with different severities of COVID-19 were similar to standard practice. RESULTS: COVID-19 clinical severity ranged from asymptomatic/mild (not requiring oxygen therapy) in 49 recipients (77%) and 63 donors (95.4%) and moderate/severe (requiring oxygen therapy) in 15 recipients (23%) and 1 donor (4.6%). Mean wait time±SEM (SD)from firstdocumentednegative reverse transcriptase-polymerase chain reaction testto surgery for recipients and donors was 90.9 ± 9.27 (74.1) and 47 ± 4.5 (29.2) days, respectively. Six episodes (9.3%) of biopsy-proven acute rejection were reported at follow-up of 214 ± 14.8 (119) days and median of 227 (interquartile range, 109-309) days. The locally weighted scatter plot smoothing curve for creatinine during follow-up in donor-recipients pairs showed no trends of increased creatinine in the context of wait time from COVID-19 to transplant surgery. No graft loss, death, reactivation/reinfection, and complications related to surgery or COVID-19 were reported. CONCLUSIONS: Our report showed excellent outcomes and follow-up data of living donor kidney transplant in recovered donor-recipient pairs with the standard immunosuppression protocol. To our knowledge, this is the first and the largest study of donor-recipient living donor kidney transplant pairs when both donors and recipients had prior COVID-19.

The First 5 Years of Uterus Transplant in the US: A Report From the United States Uterus Transplant Consortium.

Importance: Uterus transplant is a viable surgical treatment for women affected by absolute uterine-factor infertility, which affects 1 in 500 women. Objective: To review transplant and birth outcomes of uterus transplant recipients in the US since the first case in 2016. Design, Setting, and Participants: In this cohort study, 5 years of uterus transplant outcome data were collected from the 3 centers performing uterus transplants in the US: Baylor University Medical Center, Dallas, Texas; Cleveland Clinic, Cleveland, Ohio; and University of Pennsylvania, Philadelphia. A total of 33 women with absolute uterine-factor infertility who underwent uterus transplant between February 2016 and September 2021 were included. Main Outcomes and Measures: Graft survival, live birth, and neonatal outcome. Results: Of the 33 included uterus transplant recipients, 2 (6%) were Asian, 1 (3%) was Black, 1 (3%) was South Asian, and 29 (88%) were White; the mean (SD) age was 31 (4.7) years; and the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 24 (3.6). Most uterus transplant recipients (31 of 33 [94%]) had a congenitally absent uterus (Mayer-Rokitansky-Küster-Hauser syndrome), and 21 of 33 (64%) received organs from living donors. Mean (range) follow-up was 36 (1-67) months. There was no donor or recipient mortality. One-year graft survival was 74% (23 of 31 recipients). Through October 2021, 19 of 33 recipients (58%) had delivered 21 live-born children. Among recipients with a viable graft at 1 year, the proportion with a live-born child was 83% (19 of 23). The median (range) gestational age at birth of neonates was 36 weeks 6 days (30 weeks, 1 day to 38 weeks), and the median (range) birth weight was 2860 (1310-3940) g (median [range], 58th [6th-98th] percentile). No congenital malformations were detected. Conclusions and Relevance: Uterus transplant is a surgical therapy that enables women with uterine-factor infertility to successfully gestate and deliver children. Aggregate data from US centers demonstrate safety for the recipient, living donor, and child. These data may be used to counsel women with uterine-factor infertility on treatment options.

A Narrative Review COVID-19 in Solid-Organ Transplantation: Real-World Evidence From India.

Worldwide, India ranks number 2 and 3 for COVID-19 burden and absolute transplant numbers, respectively. Here, we summarized our single and multicenter Indian studies on solid-organ transplant during the COVID-19 pandemic. During the pandemic, solid-organ transplants declined 40% to 50%. The mortality rate in COVID-19-positive kidney transplant recipients (11.6%) was lower in India compared with the developed world during the first wave and lower compared with maintenance hemodialysis patients (13% to 38%) but significantly higher compared with the nonimmunosuppressed general population (1% to 3%) in India. We contributed to National Organ and Tissue Transplant Organization transplant-related guidelines to increase safety and access to solid-organ transplant. We reported the safety and feasibility of remdesivir (n = 57) and convalescent plasma therapy (n = 10) in kidney transplant recipients. We reported 100% patient and graft survival without any complications related to COVID-19 in a large cohort of kidney transplant recipients who recovered from COVID-19 (n = 372) and a large cohort of kidney transplant recipients of living donors (n = 31) who recovered from COVID-19 without any change in induction and maintenance immunosuppression. COVID-19 disease severity and mortality in the second episode (reoccurring infection) was higher (46%) compared with the first episode (11.6%). There was 4.4% incidence of COVID-19-associated mucormycosis in kidney transplant recipients with mortality of 46% in the second wave. We reported COVID-19 vaccine safety with suboptimal efficacy in kidney transplant recipients and dialysis patients compared with the general population. Our report suggested that transplant with carefully selected COVID-19-recovered donors and patients may be feasible and safe, at least over the short term. Continued research is needed on vaccine efficacy, booster doses, and long-term follow up sequelae.

Graft Inflow Modulation in Living Donor Liver Transplantation with a Small-for-Size Graft: A Systematic Review and Meta-Analysis.

Introduction: Small-for-size graft and consequently small-for-size syndrome (SFSS) is an important issue for adult living donor liver transplantation (LDLT). The optimal intra- and postoperative prevention and management strategies for SFSS remain unclear. We aimed to analyse and compare the existing strategies of portal inflow modulation (PIM) and conduct a meta-analysis of studies comparing various PIMs. The primary outcome was the incidence SFSS. Methods: The Google Scholar, Embase, PubMed, and Cochrane Library databases were systematically searched. Both fixed-and random-effects models were used to perform the meta-analysis. Results: Twenty-five studies were selected from a pool of 830 studies, of which 13 compared available surgical techniques between cohorts with and without PIM, and 12 reported outcomes of patients who underwent LDLT and developed SFSS. The incidence rate of SFSS was significantly lower in the PIM cohort than in the non-portal inflow modulation (NPIM) cohort. One-year overall survival (OS) and the re-transplantation rate were significantly better in the PIM cohort than in the NPIM cohort. Conclusion: In LDLT patients diagnosed during the reperfusion period with increased portal venous pressure and/or flow, application of PIM significantly decreased the incidence rate of SFSS and demonstrated significantly better one-year OS.

Issues regarding COVID-19 in kidney transplantation in the ERA of the Omicron variant: a commentary by the ERA Descartes Working Group.

The Omicron variant, which has become the dominant strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, brings new challenges to preventing and controlling the infection. Moreover, the widespread implementation of vaccination policies before and after transplantation, and the development of new prophylactic and treatment strategies for coronavirus disease 2019 (COVID-19) over the past 12-18 months, has raised several new issues concerning kidney transplant recipients. In this special report, the ERA DESCARTES (Developing Education Science and Care for Renal Transplantation in European States) Working Group addresses several questions related to everyday clinical practice concerning kidney transplant recipients and to the assessment of deceased and live kidney donors: what is the current risk of severe disease and of breakthrough infection, the optimal management of immunosuppression in kidney transplant recipients with COVID-19, the role of passive immunization and the efficacy of antiviral drugs in ambulatory patients, the management of drug-to-drug interactions, safety criteria for the use of SARS-CoV-2-positive donors, issues related to the use of T cell depleting agents as induction treatment, and current recommendations for shielding practices.

Utilization and outcomes of deceased donor SARS-CoV-2-positive organs for solid organ transplantation in the United States.

Coronavirus disease-19 has had a marked impact on the transplant population and processes of care for transplant centers and organ allocation. Several single-center studies have reported successful utilization of deceased donors with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests. Our aims were to characterize testing, organ utilization, and transplant outcomes with donor SARS-CoV-2 status in the United States. We used Scientific Registry of Transplant Recipients data from March 12, 2020 to August 31, 2021 including a custom file with SARS-CoV-2 testing data. There were 35 347 donor specimen SARS-CoV-2 tests, 77.5% upper respiratory samples, 94.6% polymerase chain reaction tests, and 1.2% SARS-CoV-2-positive tests. Donor age, gender, history of hypertension, and diabetes were similar by SARS-CoV-2 status, while positive SARS-CoV-2 donors were more likely African-American, Hispanic, and donors after cardiac death (p-values <.01). Recipient demographic characteristics were similar by donor SARS CoV-2 status. Adjusted donor kidney discard (odds ratio = 2.08, 95% confidence interval [CI] 1.66-2.61) was higher for SARS-CoV-2-positive donors while donor liver (odds ratio = 0.44, 95% CI 0.33-0.60) and heart recovery (odds ratio = 0.44, 95% CI 0.31-0.63) were significantly reduced. Overall post-transplant graft survival for kidney, liver, and heart recipients was comparable by donor SARS-CoV-2 status. Cumulatively, there has been significantly lower utilization of SARS-CoV-2 donors with no evidence of reduced recipient graft survival with variations in practice over time.

Effect of the COVID-19 Pandemic on Organ Donation and Transplantation in São Paulo, Brazil.

The COVID-19 pandemic has affected donation and transplantation activities in São Paulo, Brazil, as well as the patients receiving these organs. In this study, information from the database of the São Paulo Organ Allocation System was analyzed and compared 2 periods-before the pandemic and during the pandemic-to identify this effect. The COVID-19 pandemic interfered in the mortality rate and the time on the waiting list for heart, liver, pancreas, lung, and kidney transplants; the number of effective donors; and the use or disposal of available organs from deceased donors. It also reduced the transplant activity with living donors. Regarding the activity of eye tissue transplantation, the time on the waiting list increased and the number of transplant procedures decreased. The kidney transplant program was the most affected in our study. There was an increase in waiting time and mortality in the waiting list for this organ and also a decrease in kidney utilization rates.

Medium-Term Outcomes of COVID-19 Infection After Kidney Transplantation for Ongoing Living and Deceased Kidney Transplantations within the COVID-19 Pandemic.

OBJECTIVES: To present the early to midterm experience of two referral kidney transplantation centers with living and deceased kidney transplantations that were performed within the COVID-19 pandemic. MATERIALS AND METHODS: All cases performed in two referral centers in Iran within the COVID-19 pandemic were investigated. Transplantations were performed from May 2020 to February 2021. The protocol for screening included nasopharyngeal RT-PCR with chest CT scan for living and deceased transplantations in center A and RTPCR for living transplantations and chest CT scan for deceased transplantations in center B. Patients were followed for 14-26 months after transplantation regarding COVID-19 infection and its outcomes in case of infection. RESULTS: 103 kidney transplantations were performed during the study period including 54 (52.4%) living and 49 (47.6%) deceased kidney transplantations. Twenty-four recipients (23.3%) and a living donor (1%) were infected with COVID-19. The severity of COVID-19 infection was mild, moderate, severe, and critical in 16 (66.6%), 4 (16.6%), 2 (8.4%), and 2 patients (8.4%), respectively. Two mortalities were observed within transplantation recipients with COVID-19 infection (1.9%). 87.5% (7/8) COVID-19 infections in center B were observed in recipients of deceased transplantations who were screened only by chest CT scan. CONCLUSION: The results of this study indicate a low frequency of COVID-19 mortality (1.9% for the whole cohort and 8.3% within COVID-19 infected patients) for recipients of living and deceased kidney transplantation that were performed within the COVID-19 pandemic. The above findings highlight for the first time in a large study the probability of living kidney transplantation during the COVID-19 pandemic in case strict screening of donors and recipients and close supervision of operating rooms and wards are implemented. We further hypothesize the inadequacy of chest CT scan for screening of COVID-19 in kidney transplantation surgery candidates.

Successful ABO-incompatible living donor kidney transplantation in a recipient who developed flow cytometry crossmatch-positive donor-specific class I HLA antibodies following COVID-19 vaccination.

The effects of COVID-19 vaccination on alloimmunization and clinical impact in transplant candidates remain largely unknown. In a 61-year-old man who had no donor-specific antibodies (DSA) and was planned to undergo ABO-incompatible kidney transplantation (ABOi KT), DSAs (anti-A24, anti-B51, and anti-Cw14) developed after COVID-19 vaccination. After desensitization therapy, antibody level was further increased, leading to flow cytometric crossmatch-positive status. Donor-specific T cell immunity using interferon-gamma ELISPOT was continuously negative, whereas SARS-CoV-2 specific T cell immunity was intact. After confirming the C1q-negative status of DSA, the patient received ABOi KT. The patient had stable graft function and suppressed alloimmunity up to 2 months after KT. COVID-19 vaccination might relate to alloimmunization in transplant candidates, and desensitization through immune monitoring can help guide transplantation.

Survey of current transplant center practices regarding COVID-19 vaccine mandates in the United States.

An electronic survey canvassing current policies of transplant centers regarding a COVID-19 vaccine mandate for transplant candidates and living donors was distributed to clinicians at US solid organ transplant centers performing transplants from October 14, 2021-November 15, 2021. Responses were received from staff at 141 unique transplant centers. These respondents represented 56.4% of US transplant centers, and responding centers performed 78.5% of kidney transplants and 82.4% of liver transplants in the year prior to survey administration. Only 35.7% of centers reported implementing a vaccine mandate, while 60.7% reported that vaccination was not required. A minority (42%) of responding centers with a vaccine mandate for transplant candidates also mandated vaccination for living organ donors. Centers with a vaccine mandate most frequently cited clinical evidence supporting the efficacy of pre-transplant vaccination (82%) and stewardship obligations to ensure organs were transplanted into the lowest risk patients (64%). Centers without a vaccine mandate cited a variety of reasons including administrative, equity, and legal considerations for their decision. Transplant centers in the United States exhibit significant heterogeneity in COVID-19 vaccination mandate policies for transplant candidates. While all centers encourage vaccination, most centers have not mandated COVID-19 vaccination for candidates and living donors, citing administrative opposition, legal prohibitions, and concern about equity in access to transplants.

Management of regional bone bank during declaration of a state of emergency concerning the COVID-19 in Japan.

Bone banks are necessary for providing biological allografts for a series of orthopedic procedures. As nations cope with new realities driven by the 2019 coronavirus disease (COVID-19) pandemic, health-care providers, institutions, and patients share a particular concern about the effect of COVID-19 on organ donation and transplantation. Here, we describe the management of the Kitasato University Bone Bank during the state of emergency declared in response to COVID-19. Living donors received pre-operative screening by PCR, and allograft bone from COVID-19-negative donors was cryopreserved as transplantable tissues. The weekly rate of infection gradually increased from February 2-9 to April 5-11 in the dead donor-derived allograft bone-harvesting region covered by the Bank. It is becoming clear that the virus can be transmitted by asymptomatic patients, and that this route may have facilitated the spread of COVID-19. Therefore, the Bank stopped dead donor donation to consider the safety of medical staff. Three recipients received bone allografts following pre-operative COVID-19 screening by PCR. All patients were asymptomatic after bone allograft. Our experience may provide helpful information for the management of tissue banks.

A Recipient and Donor Both Have COVID-19 Disease. Should We Perform a Liver Transplant?

Coronavirus 2019 (COVID-19) is a new infectious disease that continues to spread globally. There is growing concern about donor-induced transmission of Coronavirus 2 (SARS -CoV-2). For liver transplantation, the COVID-19 PCR test is routine, in addition to epidemiological history and clinical and radiological examination 24-48 h before surgery. One of the liver transplant candidates was found to be infected with COVID-19, as well as the planned donor candidate. Since COVID-19 will be a high-risk operation for both the recipient and the donor, the operation was postponed by giving medical treatment. After the treatment and quarantine process was over, the patient and the donor then had a negative COVID-19 PCR test and the patient received a living donor liver transplant. We present a case of donor and recipient who initially both tested positive for COVID-19. This liver transplantation scenario has not previously been reported in the literature.