Results of Two Cases of Pig-to-Human Kidney Xenotransplantation.

BACKGROUND: Xenografts from genetically modified pigs have become one of the most promising solutions to the dearth of human organs available for transplantation. The challenge in this model has been hyperacute rejection. To avoid this, pigs have been bred with a knockout of the alpha-1,3-galactosyltransferase gene and with subcapsular autologous thymic tissue. METHODS: We transplanted kidneys from these genetically modified pigs into two brain-dead human recipients whose circulatory and respiratory activity was maintained on ventilators for the duration of the study. We performed serial biopsies and monitored the urine output and kinetic estimated glomerular filtration rate (eGFR) to assess renal function and xenograft rejection. RESULTS: The xenograft in both recipients began to make urine within moments after reperfusion. Over the 54-hour study, the kinetic eGFR increased from 23 ml per minute per 1.73 m2 of body-surface area before transplantation to 62 ml per minute per 1.73 m2 after transplantation in Recipient 1 and from 55 to 109 ml per minute per 1.73 m2 in Recipient 2. In both recipients, the creatinine level, which had been at a steady state, decreased after implantation of the xenograft, from 1.97 to 0.82 mg per deciliter in Recipient 1 and from 1.10 to 0.57 mg per deciliter in Recipient 2. The transplanted kidneys remained pink and well-perfused, continuing to make urine throughout the study. Biopsies that were performed at 6, 24, 48, and 54 hours revealed no signs of hyperacute or antibody-mediated rejection. Hourly urine output with the xenograft was more than double the output with the native kidneys. CONCLUSIONS: Genetically modified kidney xenografts from pigs remained viable and functioning in brain-dead human recipients for 54 hours, without signs of hyperacute rejection. (Funded by Lung Biotechnology.).

Immune response, phenotyping and molecular graft surveillance in kidney transplant recipients following severe acute respiratory syndrome coronavirus 2 vaccination.

BACKGROUND: Understanding immunogenicity and alloimmune risk following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in kidney transplant recipients is imperative to understanding the correlates of protection and to inform clinical guidelines. METHODS: We studied 50 kidney transplant recipients following SARS-CoV-2 vaccination and quantified their anti-spike protein antibody, donor-derived cell-free DNA (dd-cfDNA), gene expression profiling (GEP), and alloantibody formation. RESULTS: Participants were stratified using nucleocapsid testing as either SARS-CoV-2-naïve or experienced prior to vaccination. One of 34 (3%) SARS-CoV-2 naïve participants developed anti-spike protein antibodies. In contrast, the odds ratio for the association of a prior history of SARS-CoV-2 infection with vaccine response was 18.3 (95% confidence interval 3.2, 105.0, p < 0.01). Pre- and post-vaccination levels did not change for median dd-cfDNA (0.23% vs. 0.21% respectively, p = 0.13), GEP scores (9.85 vs. 10.4 respectively, p = 0.45), calculated panel reactive antibody, de-novo donor specific antibody status, or estimated glomerular filtration rate. CONCLUSIONS: SARS-CoV-2 vaccines do not appear to trigger alloimmunity in kidney transplant recipients. The degree of vaccine immunogenicity was associated most strongly with a prior history of SARS-CoV-2 infection.

Pig-to-human heart xenotransplantation in two recently deceased human recipients.

Genetically modified xenografts are one of the most promising solutions to the discrepancy between the numbers of available human organs for transplantation and potential recipients. To date, a porcine heart has been implanted into only one human recipient. Here, using 10-gene-edited pigs, we transplanted porcine hearts into two brain-dead human recipients and monitored xenograft function, hemodynamics and systemic responses over the course of 66 hours. Although both xenografts demonstrated excellent cardiac function immediately after transplantation and continued to function for the duration of the study, cardiac function declined postoperatively in one case, attributed to a size mismatch between the donor pig and the recipient. For both hearts, we confirmed transgene expression and found no evidence of cellular or antibody-mediated rejection, as assessed using histology, flow cytometry and a cytotoxic crossmatch assay. Moreover, we found no evidence of zoonotic transmission from the donor pigs to the human recipients. While substantial additional work will be needed to advance this technology to human trials, these results indicate that pig-to-human heart xenotransplantation can be performed successfully without hyperacute rejection or zoonosis.

Multi-institutional Collaborative Surgery Education Didactics: Virtual Adaptations During a Global Pandemic.

OBJECTIVE: The COVID-19 pandemic has disrupted graduate medical education, impacting Accreditation Council for Graduate Medical Education (ACGME)-mandated didactics. We aimed to study the utility of 2 methods of virtual learning: the daily National Surgery Resident Lecture Series (NSRLS), and weekly "SCORE School" educational webinars designed around the Surgical Council on Resident Education (SCORE) curriculum. DESIGN AND SETTING: NSRLS: The National Surgery Resident Lecture Series was a daily virtual educational session initially led by faculty at an individual surgical residency program. Thirty-eight lectures were assessed for number of live viewings (March 23, 2020-May 15, 2020). SCORE SCHOOL: Attendance at eleven weekly SCORE educational webinars was characterized into live and asynchronous viewings (May 13, 2020-August 5, 2020). Each 1-hour live webinar was produced by SCORE on a Wednesday evening and featured nationally recognized surgeon educators using an online platform that allowed for audience interaction. RESULTS: NSRLS: There were a mean of 71 live viewers per NSRLS session (range 19-118). Participation began to decline in the final 2 weeks as elective case volumes increased, but sessions remained well-attended. SCORE SCHOOL: There were a range of 164-3889 live viewers per SCORE School session. Sessions have most commonly been viewed asynchronously (89.8% of viewings). Live viewership decreased as the academic year ended and then rebounded with the start of the new academic year (range 4.9%-27%). Overall, the eight webinars were viewed 11,135 times. Each webinar continues to be viewed a mean of 43 times a day (range 0-102). Overall, the eleven webinars have been viewed a total of 22,722 times. CONCLUSIONS: Virtual didactics aimed at surgical residents are feasible, well-attended (both live and recorded), and have high levels of viewer engagement. We have observed that careful coordination of timing and topics is ideal. The ability for asynchronous viewing is particularly important for attendance. As the COVID-19 pandemic continues to disrupt healthcare systems, training programs must continue to adapt to education via virtual platforms.