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Pediatric Liver Transplantation in a Center That is Neither East Nor West [Comment]

Bruestle, Karina; Griesemer, Adam
PMID: 33201127
ISSN: 1528-1140
CID: 5151302

Embolization of a rare case of focal nodular hyperplasia in an adolescent boy

Shanmugasundaram, Srinidhi; Gioioso, Valeria; Martinez, Mercedes; Lobritto, Steven; Vittorio, Jennifer; Goldner, Dana; Griesemer, Adam; Tulin-Silver, Sheryl
ISSN: 2213-5766
CID: 5161252

Anti-CD8 Immuno-PET for Non-invasive Tracking of Early Graft Rejection in a Non-human Primate Kidney Transplant Model [Meeting Abstract]

Bruestle, K.; Tavare, R.; Fredriksson, F.; Duggan, E.; Huang, F.; Bhola, B.; Giurleo, J.; Foster, R.; Krueger, P.; Dobosz, M.; Ekanayake-Alper, D.; Sakai, H.; Piegari, B.; Castrillion, J.; Coley, S. M.; Harari, O.; Mintz, A.; Ma, D.; Griesemer, A.
ISSN: 1600-6135
CID: 5161242

Center Use of Technical Variant Grafts Impacts Pediatric Liver Transplant Waitlist and Recipient Outcomes in the United States [Meeting Abstract]

Mazariegos, G.; Perito, E. R.; Squires, J.; Soltys, K.; Griesemer, A.; Taylor, S. A.; Pahl, E.
ISSN: 1600-6135
CID: 5161212

A case of an Infant with SARS-CoV-2 hepatitis early after liver transplantation [Case Report]

Heinz, Nicole; Griesemer, Adam; Kinney, Joanna; Vittorio, Jennifer; Lagana, Stephen M; Goldner, Dana; Velasco, Monica; Kato, Tomoaki; Lobritto, Steven; Martinez, Mercedes
We present a case of a pediatric liver transplant recipient diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection four days after receiving a living donor liver allograft from her mother. The recipient was a 6-month-old with end-stage liver disease due to biliary atresia and failed Kasai. The infant had an uncomplicated implantation, excellent graft function and down-trending liver enzymes until developing fevers, diarrhea, and moderate respiratory distress requiring non-invasive respiratory support. SARS-CoV-2 testing (nasal swab Polymerase Chain Reaction) was positive on post-operative day (POD) 4. Liver enzymes peaked ~1000 U/L (5-fold higher than the previous day) on POD 6. Histology demonstrated a mixed picture of moderate acute hepatitis and classical elements of mild to moderate acute cellular rejection. Her hepatitis and respiratory symptoms improved coincident with completing treatment with hydroxychloroquine, reduced immunosuppression, and intravenous gamma globulin (IVIG).
PMID: 32559354
ISSN: 1399-3046
CID: 5151252

Ex Vivo Resection and Autotransplantation for Conventionally Unresectable Tumors - An 11-year Single Center Experience

Kato, Tomoaki; Hwang, Regina; Liou, Peter; Weiner, Joshua; Griesemer, Adam; Samstein, Benjamin; Halazun, Karim; Mathur, Abhishek; Schwartz, Gary; Cherqui, Daniel; Emond, Jean
BACKGROUND AND AIMS:Ex vivo surgery may provide a chance at R0 resection for conventionally unresectable tumors. However, long-term outcomes have not been well documented. In this study, we analyze our 11-year outcomes to define its role. STUDY DESIGN:We retrospectively analyzed 46 consecutive patients who underwent ex vivo surgery at our institution 2008-2019. RESULTS:The types of tumors were: carcinoma (n = 20), sarcoma (n = 20) and benign to low grade tumor (n = 6). The type of ex vivo surgery was chosen based on tumor location and vascular involvement. The most commonly performed procedure was ex vivo hepatectomy (n = 18), followed by ex vivo resection and intestinal autotransplantation (n = 12), ex vivo Whipple procedure and liver autotransplantation (n = 8) and multivisceral ex vivo procedure (n = 7). Twenty-three patients (50%) are currently alive with median follow-up of 4.0-years (11 months-11.8 years). The overall survival was 70%/59%/52%, at 1-/3-/5-years, respectively. Patient survival for benign to low grade tumors, sarcoma, and carcinoma was 100%/100%/100%, 65%/60%/50%, and 65%/45%/40%, at 1-/3-/5-years, respectively. Ninety-one percent patients had R0 resection, and 57% had no recurrence to date with median follow-up of 3.1-years. Two patients (4.3%) died within 30 days due to sepsis and gastroduodenal artety (GDA) stump blowout. Two additional patients died between 30 and 90 days due to sepsis. Perioperative mortality in the last 23 consecutive cases was limited to 1 patient who died of sepsis between 30 and 90 days. CONCLUSIONS:For a selected group of patients with conventionally unresectable tumors, ex vivo surgery can offer effective surgical removal with a reasonably low perioperative mortality at experienced centers.
PMID: 32833756
ISSN: 1528-1140
CID: 5143512

Progress towards xenogenic tolerance

Duggan, Erin M; Griesemer, Adam
PURPOSE OF REVIEW:To describe the most recent progress towards tolerance in xenotransplantation. RECENT FINDINGS:Mixed chimerism and thymic transplantation have been used to promote tolerance in xenotransplantation models. Intra-bone bone marrow transplantation is a recent advance for mixed chimerism, which promotes longer lasting chimerism and early graft function of subsequent organ transplantation. The hybrid thymus, an advancement to the vascularized thymokidney and vascularized thymic lobe, is being developed to allow for both donor and recipient T-cell selection in the chimeric thymus, encouraging tolerance to self and donor while maintaining appropriate immune function. Regulatory T cells show promise to promote tolerance by suppressing effector T cells and by supporting mixed chimerism. Monoclonal antibodies such as anti-CD2 may promote tolerance through suppression of CD2+ effector and memory T cells whereas Tregs, which express lower numbers of CD2, are relatively spared and might be used to promote tolerance. SUMMARY:These findings contribute major advances to tolerance in xenotransplantation. A combination of many of these mechanisms will likely be needed to have long-term tolerance maintained without the use of immunosuppression.
PMID: 32796179
ISSN: 1531-7013
CID: 5151282

Transient-mixed Chimerism With Nonmyeloablative Conditioning Does Not Induce Liver Allograft Tolerance in Nonhuman Primates

Chaudhry, Sulemon; Kato, Yojiro; Weiner, Joshua; Alonso-Guallart, Paula; Baker, Sam; Woodland, David C; Lefkowitch, Jay H; Duran-Struuck, Raimon; Sondermeijer, Hugo P; Zitsman, Jonah; Sears, Mallory L; Wu, Anette; Karolewski, Brian; Houck, Philipp J; Martinez, Mercedes; Kato, Tomoaki; Sykes, Megan; Griesemer, Adam D
BACKGROUND:Although short-term outcomes for liver transplantation have improved, patient and graft survival are limited by infection, cancer, and other complications of immunosuppression. Rapid induction of tolerance after liver transplantation would decrease these complications, improving survival and quality of life. Tolerance to kidneys, but not thoracic organs or islets, has been achieved in nonhuman primates and humans through the induction of transient donor chimerism. Since the liver is considered to be tolerogenic, we tested the hypothesis that the renal transplant transient chimerism protocol would induce liver tolerance. METHODS:Seven cynomolgus macaques received immune conditioning followed by simultaneous donor bone marrow and liver transplantation. The more extensive liver surgery required minor adaptations of the kidney protocol to decrease complications. All immunosuppression was discontinued on postoperative day (POD) 28. Peripheral blood chimerism, recipient immune reconstitution, liver function tests, and graft survival were determined. RESULTS:The level and duration of chimerism in liver recipients were comparable to those previously reported in renal transplant recipients. However, unlike in the kidney model, the liver was rejected soon after immunosuppression withdrawal. Rejection was associated with proliferation of recipient CD8 T effector cells in the periphery and liver, increased serum interleukin (IL)-6 and IL-2, but peripheral regulatory T cell (Treg) numbers did not increase. Antidonor antibody was also detected. CONCLUSIONS:These data show the transient chimerism protocol does not induce tolerance to livers, likely due to greater CD8 T cell responses than in the kidney model. Successful tolerance induction may depend on greater control or deletion of CD8 T cells in this model.
PMID: 32732835
ISSN: 1534-6080
CID: 5151272

Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs

Hozain, Ahmed E; O'Neill, John D; Pinezich, Meghan R; Tipograf, Yuliya; Donocoff, Rachel; Cunningham, Katherine M; Tumen, Andrew; Fung, Kenmond; Ukita, Rei; Simpson, Michael T; Reimer, Jonathan A; Ruiz, Edward C; Queen, Dawn; Stokes, John W; Cardwell, Nancy L; Talackine, Jennifer; Kim, Jinho; Snoeck, Hans-Willem; Chen, Ya-Wen; Romanov, Alexander; Marboe, Charles C; Griesemer, Adam D; Guenthart, Brandon A; Bacchetta, Matthew; Vunjak-Novakovic, Gordana
Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering.
PMID: 32661401
ISSN: 1546-170x
CID: 5151262

COVID-19 Associated Hepatitis Complicating Recent Living Donor Liver Transplantation

Lagana, Stephen M; De Michele, Simona; Lee, Michael J; Emond, Jean C; Griesemer, Adam D; Tulin-Silver, Sheryl A; Verna, Elizabeth C; Martinez, Mercedes; Lefkowitch, Jay H
We present a case of COVID-19 hepatitis in a living donor liver allograft recipient whose donor subsequently tested positive for COVID-19. The patient is a female infant with biliary atresia (failed Kasai procedure). She recovered well, with improving liver function tests for 4 days. On post-operative day (POD) 4 the patient developed respiratory distress and fever. COVID-19 testing (polymerase chain reaction) was positive. Liver function tests increased approximately 5-fold. Liver biopsy showed moderate acute hepatitis with prominent clusters of apoptotic hepatocytes and associated cellular debris. Lobular lymphohistiocytic inflammation was noted. Typical portal features of mild to moderate acute cellular rejection were also noted.
PMID: 32302212
ISSN: 1543-2165
CID: 4383892