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Article ; Online: Physiologic considerations of pig-to-human kidney xenotransplantation.

Tatapudi, Vasishta S / Griesemer, Adam D

Current opinion in nephrology and hypertension

2022 Volume 32, Issue 2, Page(s) 193–198

Abstract: Purpose of review: The greatest challenge facing end-stage kidney disease (ESKD) patients is the scarcity of transplantable organs. Advances in genetic engineering that mitigate xenogeneic immune responses have made transplantation across species a ... ...

Abstract	Purpose of review: The greatest challenge facing end-stage kidney disease (ESKD) patients is the scarcity of transplantable organs. Advances in genetic engineering that mitigate xenogeneic immune responses have made transplantation across species a potentially viable solution to this unmet need. Preclinical studies and recent reports of pig-to-human decedent renal xenotransplantation signify that clinical trials are on the horizon. Here, we review the physiologic differences between porcine and human kidneys that could impede xenograft survival. Topics addressed include porcine renin and sodium handling, xenograft water handling, calcium, phosphate and acid-base balance, responses to porcine erythropoietin and xenograft growth. Recent findings: Studies in nonhuman primates (NHPs) have demonstrated that genetically modified pig kidneys can survive for an extended period when transplanted into baboons. In recent studies conducted by our group and others, hyperacute rejection did not occur in pig kidneys lacking the α1,3Gal epitope transplanted into brain-dead human recipients. These experimental trials did not study potential clinical abnormalities arising from idiosyncratic xenograft responses to human physiologic stimuli due to the brief duration of observation this model entails. Summary: Progress in biotechnology is heralding an era of xenotransplantation. We highlight the physiologic considerations for xenogeneic grafts to succeed.
MeSH term(s)	Animals ; Humans ; Swine ; Animals, Genetically Modified ; Transplantation, Heterologous ; Kidney/physiology ; Kidney Transplantation ; Graft Rejection
Language	English
Publishing date	2022-11-17
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	1151092-4
ISSN	1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
ISSN (online)	1473-6543 ; 1535-3842
ISSN	1062-4813 ; 1062-4821
DOI	10.1097/MNH.0000000000000858
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Zs.A 3686: Show issues

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Article ; Online: The decedent model: A new paradigm for de-risking high stakes clinical trials like xenotransplantation.

Montgomery, Robert A / Griesemer, Adam D / Segev, Dorry L / Sommer, Philip

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2024 Volume 24, Issue 4, Page(s) 526–532

Abstract: The first 2 living recipients of pig hearts died unexpectedly within 2 months, despite both recipients receiving what over 30 years of nonhuman primate (NHP) research would suggest were the optimal gene edits and immunosuppression to ensure success. ... ...

Abstract	The first 2 living recipients of pig hearts died unexpectedly within 2 months, despite both recipients receiving what over 30 years of nonhuman primate (NHP) research would suggest were the optimal gene edits and immunosuppression to ensure success. These results prompt us to question how faithfully data from the NHP model translate into human outcomes. Before attempting any further heart xenotransplants in living humans, it is highly advisable to gain a more comprehensive understanding of why the promising preclinical NHP data did not accurately predict outcomes in humans. It is also unlikely that additional NHP data will provide more information that would de-risk a xenoheart clinical trial because these cases were based on the best practices from the most successful NHP results to date. Although imperfect, the decedent model offers a complementary avenue to determine appropriate treatment regimens to control the human immune response to xenografts and better understand the biologic differences between humans and NHP that could lead to such starkly contrasting outcomes. Herein, we explore the potential benefits and drawbacks of the decedent model and contrast it to the advantages and disadvantages of the extensive body of data generated in the NHP xenoheart transplantation model.
MeSH term(s)	Humans ; Animals ; Swine ; Transplantation, Heterologous ; Heterografts ; Immunosuppression Therapy
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1016/j.ajt.2024.01.035
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Article ; Online: Pediatric Living Donor Liver Transplantation: Optimizing Outcomes for Recipients, Donors, and the Waiting List.

Duggan, Erin M / Griesemer, Adam D

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society

2021 Volume 28, Issue 3, Page(s) 359–360

MeSH term(s)	Child ; Humans ; Liver Transplantation/adverse effects ; Living Donors ; Tissue Donors ; Tissue and Organ Procurement ; Waiting Lists
Language	English
Publishing date	2021-12-08
Publishing country	United States
Document type	Editorial
ZDB-ID	2006866-9
ISSN	1527-6473 ; 1527-6465
ISSN (online)	1527-6473
ISSN	1527-6465
DOI	10.1002/lt.26378
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Zs.A 4702: Show issues

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Article ; Online: Size Is Not Everything: "Small" Living Donor Liver Transplantation Grafts Can Have Good Outcomes.

Sakai, Hiroshi / Duggan, Erin M / Griesemer, Adam D

Transplantation

2021 Volume 105, Issue 9, Page(s) 1917–1918

MeSH term(s)	Graft Survival ; Humans ; Liver ; Liver Transplantation ; Living Donors
Language	English
Publishing date	2021-10-27
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000003473
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Article ; Online: Transplantation tolerance in nonhuman primates and humans.

Sykes, Megan / Griesemer, Adam D

Bone marrow transplantation

2019 Volume 54, Issue Suppl 2, Page(s) 815–821

Abstract: This review focuses on our recent studies involving nonmyeloablative bone marrow transplantation as an approach to inducing organ allograft tolerance across MHC barriers in nonhuman primates and in patients. The clinical studies are focused on mechanisms ...

Abstract	This review focuses on our recent studies involving nonmyeloablative bone marrow transplantation as an approach to inducing organ allograft tolerance across MHC barriers in nonhuman primates and in patients. The clinical studies are focused on mechanisms of tolerance involved in a protocol carried out at Massachusetts General Hospital in HLA-mismatched haploidentical combinations for the induction of renal allograft tolerance. These studies, in which chimerism was only transient and GVHD did not occur, suggest an early role for donor-specific regulatory T cells in tolerance induction, followed by partial and gradual deletion of donor-reactive T cells. We utilized high-throughput sequencing methodologies in a novel way to identify and track large numbers of alloreactive T cell receptors (TCRs). This method has been shown to identify biologically significant alloreactive TCRs in transplant patients and pointed to clonal deletion as a major mechanism of long-term tolerance in these patients. More recently, we adapted this sequencing method to optimally identify the donor-specific regulatory T cell (Treg) repertoire. Interrogation of the early posttransplant repertoire demonstrated expansion of donor-specific Tregs in association with tolerance. Our studies suggest a role for the kidney graft in tolerance by these mechanisms in patients who had only transient chimerism. Nonhuman primate studies indicate that other organs, including the heart, the lungs and the liver, are less readily tolerated following a period of transient mixed chimerism. Our efforts to extend the reach of mixed chimerism for tolerance induction beyond the kidney are therefore focused on the addition of recipient Tregs to the protocol. This approach has the potential to enhance chimerism while further reducing the risk of GVHD.
MeSH term(s)	Animals ; Humans ; Primates ; Transplantation Tolerance/physiology
Language	English
Publishing date	2019-08-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/s41409-019-0620-3
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Zs.A 2168: Show issues

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Article ; Online: Tolerance in clinical liver transplantation: The long road ahead.

Emond, Jean C / Griesemer, Adam D

Hepatology (Baltimore, Md.)

2017 Volume 65, Issue 2, Page(s) 411–413

Language	English
Publishing date	2017-02
Publishing country	United States
Document type	Editorial
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.28862
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Zs.A 1660: Show issues

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Article ; Online: Big improvements for the smallest recipients.

Griesemer, Adam D / Emond, Jean C

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society

2017 Volume 23, Issue 8, Page(s) 997–998

Language	English
Publishing date	2017-08
Publishing country	United States
Document type	Editorial
ZDB-ID	2006866-9
ISSN	1527-6473 ; 1527-6465
ISSN (online)	1527-6473
ISSN	1527-6465
DOI	10.1002/lt.24802
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Article ; Online: Center use of technical variant grafts varies widely and impacts pediatric liver transplant waitlist and recipient outcomes in the United States.

Mazariegos, George V / Perito, Emily R / Squires, James E / Soltys, Kyle A / Griesemer, Adam D / Taylor, Sarah A / Pahl, Eric

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society

2023 Volume 29, Issue 7, Page(s) 671–682

Abstract: To assess the impact of technical variant grafts (TVGs) [including living donor (LD) and deceased donor split/partial grafts] on waitlist (WL) and transplant outcomes for pediatric liver transplant (LT) candidates, we performed a retrospective analysis ... ...

Abstract	To assess the impact of technical variant grafts (TVGs) [including living donor (LD) and deceased donor split/partial grafts] on waitlist (WL) and transplant outcomes for pediatric liver transplant (LT) candidates, we performed a retrospective analysis of Organ Procurement and Transplantation Network (OPTN) data on first-time LT or liver-kidney pediatric candidates listed at centers that performed >10 LTs during the study period, 2004-2020. Center variance was plotted for LT volume, TVG usage, and survival. A composite center metric of TVG usage and WL mortality was developed to demonstrate the existing variation and potential for improvement. Sixty-four centers performed 7842 LTs; 657 children died on the WL. Proportions of WL mortality by center ranged from 0% to 31% and those of TVG usage from 0% to 76%. Higher TVG usage, from deceased donor or LD, independently or in combination, significantly correlated with lower WL mortality. In multivariable analyses, death from listing was significantly lower with increased center TVG usage (HR = 0.611, CI: 0.40-0.92) and LT volume (HR = 0.995, CI: 0.99-1.0). Recipients of LD transplants (HR = 0.637, CI: 0.51-0.79) had significantly increased survival from transplant compared with other graft types, and recipients of deceased donor TVGs (HR = 1.066, CI: 0.93-1.22) had statistically similar outcomes compared with whole graft recipients. Increased TVG utilization may decrease WL mortality in the US. Hence, policy and training to increase TVG usage, availability, and expertise are critical.
MeSH term(s)	Child ; Humans ; United States/epidemiology ; Liver Transplantation/adverse effects ; Retrospective Studies ; Liver ; Tissue and Organ Procurement ; Living Donors ; Graft Survival
Language	English
Publishing date	2023-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2006866-9
ISSN	1527-6473 ; 1527-6465
ISSN (online)	1527-6473
ISSN	1527-6465
DOI	10.1097/LVT.0000000000000091
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Article ; Online: Advancing the Field of Pediatric Liver Transplantation: Urgent Action Items Identified During the 2022 Society of Pediatric Liver Transplantation Meeting.

Feldman, Amy G / Adams, Megan / Griesemer, Adam D / Horslen, Simon / Kelly, Beau / Mavis, Alisha M / Mazariegos, George V / Ng, Vicky L / Perito, Emily R / Rodriguez-Davalos, Manuel I / Squires, James E / Tiao, Greg / Yanni, George S / Hsu, Evelyn K

Transplantation

2023 Volume 107, Issue 6, Page(s) 1223–1225

MeSH term(s)	Humans ; Child ; Liver Transplantation
Language	English
Publishing date	2023-05-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004584
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Zs.A 488: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Risk Factors for 30-Day Unplanned Readmission After Hepatectomy: Analysis of 438 Pediatric Patients from the ACS-NSQIP-P Database.

Kang, Elise / Shin, John Inho / Griesemer, Adam D / Lobritto, Steven / Goldner, Dana / Vittorio, Jennifer M / Stylianos, Steven / Martinez, Mercedes

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract

2021 Volume 25, Issue 11, Page(s) 2851–2858

Abstract: Background: Hepatic resections are uncommon in children. Most studies reporting complications of these procedures and risk factors associated with unplanned readmissions are limited to retrospective data from single centers. We investigated risk factors ...

Abstract	Background: Hepatic resections are uncommon in children. Most studies reporting complications of these procedures and risk factors associated with unplanned readmissions are limited to retrospective data from single centers. We investigated risk factors for 30-day unplanned readmission after hepatectomy in children using the American College of Surgeons National Surgical Quality Improvement-Pediatric database. Methods: The database was queried for patients aged 0-18 years who underwent hepatectomy for the treatment of liver lesions from 2012 to 2018. Chi-squared tests were performed to evaluate for potential risk factors for unplanned readmissions. A multivariate regression analysis was performed to identify independent predictors for unplanned 30-day readmissions. Results: Among 438 children undergoing hepatectomy, 64 (14.6%) had unplanned readmissions. The median age of the hepatectomy cohort was 1 year (0-17); 55.5% were male. Patients readmitted had significantly higher rates of esophageal/gastric/intestinal disease (26.56% vs. 14.97%; p=0.022), current cancer (85.94% vs. 75.67%; p=0.012), and enteral and parenteral nutritional support (31.25% vs. 17.65%; p=0.011). Readmitted patients had significantly higher rates of perioperative blood transfusion (67.19% vs. 52.41%; p=0.028), organ/space surgical site infection (10.94% vs. 1.07%; p<.001), sepsis (15.63% vs. 3.74%; p<.001), and total parenteral nutrition at discharge (9.09% vs. 2.66%; p=0.041). Organ/space surgical site infection was an independent risk factor for unplanned readmission (OR=9.598, CI [2.070-44.513], p=0.004) by multivariable analysis. Conclusion: Unplanned readmissions after liver resection are frequent in pediatric patients. Organ/space surgical site infections may identify patients at increased risk for unplanned readmission. Strategies to reduce these complications may decrease morbidity and costs associated with unplanned readmissions.
MeSH term(s)	Child ; Databases, Factual ; Hepatectomy/adverse effects ; Humans ; Male ; Patient Readmission ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Retrospective Studies ; Risk Factors ; Surgical Wound Infection ; Time Factors
Language	English
Publishing date	2021-04-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2012365-6
ISSN	1873-4626 ; 1934-3213 ; 1091-255X
ISSN (online)	1873-4626 ; 1934-3213
ISSN	1091-255X
DOI	10.1007/s11605-021-04995-2
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