Thoracic transplantation

Note on Sources: The articles in this supplement are based on the reference tables in the 2002 OPTN/SRTR Annual Report, which are not included in this publication. Many relevant data appear in figures and tables directly referred to in the article; other tables from the Annual Report that serve as the basis for this article include the following: Tables 1.5, 1.6, 1.12, 1.13, 11.1–11.4, 11.8, 11.9, 12.1–12.4, 12.7–12.9, 13.1–13.4, and 13.7–13.9. All of these tables are also available online at http://www.ustransplant.org.The Scientific Registry of Transplant Recipients (SRTR) is funded by contract #231-00-0116 from the Health Resources and Services Administration (HRSA). The views expressed herein are those of the authors and not necessarily those of the US Government. This is a US Government-funded work. There are no restrictions on its use.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91976/1/2003 AJT Thoracic Transplantation.pd

Applications of BMI or BSI: Differences and Revisions According to Age and Height

Validation of body-mass relationships requires a careful statistical analysis of data of normal weight individuals. BMI (ratio between body mass and square of body height) and BSI values (ratio between mass and cube of body height) have been calculated for 99 persons with ages between 1 day and 76 years. These BMI or BSI values have been used for least squares fits yielding mean BMI or BSI values, their variances (providing precision), and average deviations of individual BMI/BSI values from the BMI/BSI means. The latter allows limits to over- and underweight. For adults we found mean values of BSI of 12.36 and confirmed 21.7 for the mean BMI; but the BSI was 1.4 times more precise than the BMI. For children shorter than 1.3 m and younger than 8 years we found the BMI average of 15.9 and over-/underweight limits of 17.4/14.4 being significantly smaller than and incompatible with the recommended BMI values

Physiological models of body composition and human obesity

Correction to Levitt DG, Heymsfield SB, Pierson Jr RN, Shapses SA, Kral JG: Physiological models of body composition and human obesity. Nutrition & Metabolism 2007, 4:1

Leukocyte dynamics in Cynomolgus monkeys following heterotopic heart allotransplantation under costimulation pathway blockade

RationaleIt was hypothesized that the dynamics of leukocyte populations in peripheral blood (PB) or peri-graft lymph nodes (LNs) in cynomolgus monkey recipients of a heterotopic heart allotransplant, completed with the determination of graft-infiltrating lymphocyte (GIL) populations at explant, may vary in association with immune rejection mechanisms or immunomodulatory treatments.MethodsAmong 15 cynomolgus monkey recipients of heterotopic heart allografts, 13 were treated with a variety of costimulation-blocking immunosuppressive (IS) agents targeting CD80/CD86, CD28, CD40, or CD154, and two were untreated (controls). Leukocyte populations were characterized using hemocytometry and flow cytometry.ResultsIn PB, neutrophils and monocytes increased significantly (p < 0.001) during the first 2 weeks after transplant. Eosinophils and monocytes steadily increased after transplant, peaking around the time of graft failure (p < 0.01), a trend most prominent in association with belatacept. After the initial nadir on day 1 after transplant, PB lymphocytes increased steadily, particularly in association with belatacept and hu5c8, to a peak 1 week before graft rejection (p < 0.05), like CD3 cells. In PB, the CD4/CD8 ratio consistently trended down in all treated groups, most prominently in association with 5c8. In LNs at explant, CD4 cells outnumbered CD8 cells (p < 0.001), whereas in graft-infiltrating lymphocytes (GILs), CD8 cells predominated (p < 0.001). Among GILs at the time of rejection, CD8+CD62− central and effector memory cells were prominent, along with CD4+CD8+ T cells and IgD−CD27− B cells. At explant time, analysis of CD3 CD127lowCD25highFoxp3+ cell populations identified in GILs two clusters of CD4+CD8+ and three clusters of CD8 cells, which were expanded relative to PB or LNs.ConclusionsObservations regarding CD8 T-cell subpopulations in PB, LNs, and GILs support the conventional paradigm regarding their role as key effector cells mediating graft injury. The prominence of CD4+CD8+CD127lowCD25highFoxp3+ T cells and that of IgD−CD27− B cells among GILs have not previously been described. Expansion of circulating eosinophils around the time of rejection may implicate these cells in rejection mechanisms. Comparison of graft lymphocyte subpopulations with LNs or PB highlights mechanistically plausible differences that justify further efforts to elucidate their roles in graft injury and protection as a strategy to identify new candidate approaches to prevent rejection and promote tolerance

Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft

Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and alpha CD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed alpha CD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of aCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days

Physiological models of body composition and human obesity

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Third WHO Global Consultation on regulatory requirements for xenotransplantation clinical trials, Changsha, Hunan, China December 12-14, 2018: "The 2018 Changsha Communiqué" The 10-Year Anniversary of The International Consultation on Xenotransplantation

After feedback from the working parties, the final session focused on drafting proposed revisions of the WHO documents, and resulted in the formulation of the draft “Third WHO Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials, The 2018 Changsha Communiqué.” This draft was submitted to WHO in February 2019 for WHO and World Health Assembly consideration. If approved, the 2018 Changsha Communiqué will then be posted on the websites of WHO, IXA, and TTS, and published in Xenotransplantation. This report includes summaries of the various sessions, followed by the abstracts of invited speakers from the update sessions

Religious perspectives regarding the ethical issues associated with clinical xenotransplantation

Background: As xenotransplantation advances toward clinical trials, viewpoints from various segments of society are continually needed to engage the public and to inform the prospective clinical trials. As the majority of the world's population identifies with a religious tradition, religious perspectives regarding the ethical issues associated with clinical xenotransplantation are an important element to take into account. Methods: At the 2024 Congress of The Transplantation Society in Istanbul, Türkiye, a group of religious scholars from Catholicism, The Church of Jesus Christ of Latter-day Saints, Hinduism, Shia Islam, Judaism, Protestant Christianity, and the African American religious traditions met together to discuss viewpoints toward xenotransplantation from their respective religious tradition. Additional contributions were received from representatives from the American Anglican Episcopal Church and Sunni Islam faith traditions. Results: Each speaker presented viewpoints on the ethical issues associated with clinical xenotransplantation from their own religious perspective. Common issues that were raised include the treatment and stewardship of animals, xenozoonotic infection and other risks, while religious dictums of particular relevance for each faith tradition were noted. Conclusion: Overall, none of the participants considered xenotransplantation to be impermissible within their religious tradition. Yet, it is important to note that persons of religious faith may come to different conclusions from their coreligionists about the permissibility of xenotransplantation as a personal choice or as spokespersons for others of their faith. Additional empirical viewpoint data from each religious tradition will be helpful to further inform normative views and measure the impact of public education. As xenotransplantation continues to advance to the clinic, continued exploration of religious perspectives is needed to best support individual decision-making and optimize patient-centered care