Giuliano Testa M.D.

Jones, B. P., S. Saso, T. Bracewell-Milnes, M. Y. Thum, J. Nicopoullos, C. Diaz-Garcia, P. Friend, S. Ghaem-Maghami, G. Testa, L. Johannesson, I. Quiroga, J. Yazbek and J. R. Smith (2019). “Human uterine transplantation: a review of outcomes from the first 45 cases.” BJOG 126(11): 1310-1319.

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Uterine transplantation restores reproductive anatomy in women with absolute uterine factor infertility and allows the opportunity to conceive, experience gestation, and acquire motherhood. The number of cases being performed is increasing exponentially, with detailed outcomes from 45 cases, including nine live births, now available. In light of the data presented herein, including detailed surgical, immunosuppressive and obstetric outcomes, the feasibility of uterine transplantation is now difficult to refute. However, it is associated with significant risk with more than one-quarter of grafts removed because of complications, and one in ten donors suffering complications requiring surgical repair. TWEETABLE ABSTRACT: Uterine transplantation is feasible in women with uterine factor infertility, but is associated with significant risk of complication.

Lawrence, M. C., C. M. Darden, S. Vasu, K. Kumano, J. Gu, X. Wang, J. Chan, Z. Xu, B. F. Lemoine, P. Nguyen, C. Smitherman, B. Naziruddin and G. Testa (2019). “Profiling Gene Programs in the Blood during Liver Regeneration in Living Liver Donors.” Liver Transpl Jul 24. [Epub ahead of print].

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The human liver’s capacity to rapidly regenerate to a full-sized functional organ after resection has allowed successful outcomes for living-donor liver transplantation (LDLT) procedures. However, the ability to detect and track physiological changes occurring during liver regeneration after resection and throughout the restoration process is still lacking. We performed a comprehensive whole-transcriptome RNA sequencing analysis of liver and circulating blood tissue from 12 healthy LDLT donors to define biomarker signatures for monitoring physiological activities during liver regeneration at 14 time points for up to 1 year procedural follow up. LDLT donor liver tissue differentially expressed 1238 coding and noncoding genes post resection, and an additional 1260 genes were selectively regulated post-LDLT. A total of 15,011 RNA transcript species were identified in the blood in response to liver resection. Transcripts most highly regulated were sequentially expressed within three distinct peaks that correlated with sets of functional genes involved in induction of liver resection-specific innate immune response (Peak I), activation of the complement system (Peak II), and platelet activation and erythropoiesis (Peak III). Each peak corresponded with progressive phases of extracellular matrix degradation, remodeling, and organization during liver restoration. These processes could be tracked by distinct molecular signatures of upregulated and downregulated gene profiles in the blood during phases of liver repair and regeneration. In conclusion, the results establish temporal and dynamic transcriptional patterns of gene expression following surgical liver resection that can be detected in the blood and potentially used as biomarker signatures for monitoring phases of liver regeneration.

Johannesson, L., A. Wall, J. M. Putman, L. Zhang, G. Testa and C. Diaz-Garcia (2019). “Rethinking the time interval to embryo transfer after uterus transplantation-DUETS (Dallas UtErus Transplant Study).” BJOG Jul 8. [Epub ahead of print].

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The first successful live birth after uterus transplantation occurred in 2014. Since then, successful live births have been replicated, offering hope to women with uterine factor infertility who want to carry a pregnancy . . . Uterus transplant can allow women to carry their own pregnancy. Because of the transplant operation, infectious disease risks, and immunosuppressive medications, these pregnancies require careful planning. Conditions to achieve before ET include stable uterine graft function, absence of active rejection, stable immunosuppressive medication with agents with low teratogenic risk, and low‐risk status for harmful opportunistic infections. Our experience, the experience of other uterus transplant programmes, and results of successful pregnancies in other solid organ transplant recipients suggest ET could be considered as soon as 3 months after uterus transplantation if the above criteria are met. Given the unique characteristics of uterus transplantation and the recipient population, the transplant‐to‐ET interval should differ from recommendations in other organ and vascular allograft transplantations. The incentive of minimising the recipient‐graft time and concomitant exposure to immunosuppressants in this young, healthy patient population strongly supports shortening the transplant‐to‐ET time. (Excerpts from text, p. 1, 4; no abstract available.)

Testa, G. and L. Johannesson (2019). “Letter to the Editor: Current status and future direction of uterus transplantation.” Curr Opin Organ Transplant 24(1): 4.

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We would like to direct your attention to a statement written in the article “Current status and future direction of uterus transplantation” authored by Dr. Mats Brannstrom and published in Current Opinion in Organ Transplantation, October 2018. In the Section, “Live Donor Uterus Transplantation: Results”, it is stated that “Although the case proved to be successful, it has to be pointed out that bilateral use of utero-ovarian veins will necessitate donor oophorectomy and this will lead to premature menopause, with may lead to increase morbidity in this 32-year-old altruistic donor.” This statement is incorrect. In the publication announcing the first live birth after uterus transplantation in the United States, G. Testa et al. American Journal of Transplantion, May 2018, we clearly specified that “The utero ovarian veins were identified as they run closely to the fallopian and dissected free from the ovary. The ovaries were left in situ.” This donor surgical technique has been used routinely by us. In fact, the second mother to give birth in our programme also received a uterus transplant in which the venous outflow was based exclusively on the utero-ovarian vein segment and who donor did not require and oophorectomy. We thank you for the attention given to reporting the correct information. (Excerpt from text of this correspondence; no abstract available.)

Idriss, R., J. Hasse, T. Wu, F. Khan, G. Saracino, G. McKenna, G. Testa, J. Trotter, G. Klintmalm and S. K. Asrani (2019). “Impact of Prior Bariatric Surgery on Perioperative Liver Transplant Outcomes.” Liver Transpl 25(2): 217-227.

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Bariatric surgery (BS) is effective in treating morbid obesity, but the impact of prior BS on candidacy for liver transplantation (LT) is unclear. We examined 78 patients with cirrhosis with prior BS compared with a concurrent cohort of 156 patients matched by age, Model for End-Stage Liver Disease score, and underlying liver disease. We compared rates of transplant denial after evaluation, delisting on the waiting list, and survival after LT. The median time from BS to LT evaluation was 7 years. Roux-en-Y gastric bypass was the most common BS procedure performed (63% of cohort). Nonalcoholic fatty liver disease was the leading etiology for liver cirrhosis (47%). Delisting/death on the waiting list was higher among patients with BS (33.3% versus 10.1%; P = 0.002), and the transplantation rate was lower (48.9% versus 65.2%; P = 0.03). Intention-to-treat (ITT) survival from listing to 1 year after LT was lower in the BS cohort versus concurrent cohort (1-year survival, 84% versus 90%; P = 0.05). On adjusted analysis, a history of BS was associated with an increased risk of death on the waiting list (hazard ratio [HR], 5.7; 95% confidence interval [CI], 2.2-15.1), but this impact was attenuated (HR, 4.9; 95% CI, 1.8-13.4) by the presence of malnutrition. When limited to matched controls by sex, mortality attributed to BS was no longer significant for females (P = 0.37) but was significant for males (P = 0.046). Sarcopenia, as captured by skeletal muscle index, was calculated in a subset of patients (n = 49). The total skeletal surface area was lower in the BS group (127 [105-141] cm(2) versus 153 [131-191] cm(2) ; P = 0.005). Rates of sarcopenia were higher among patients delisted after listing (71.4% versus 16.7%; P = 0.04). In conclusion, a history of BS was associated with higher rates of delisting on the waiting list as well as lower survival from the time of listing on ITT analysis. Presence of malnutrition and sarcopenia among patients with BS may contribute to worse outcomes.