Research Spotlight

Kalecký, K., German, D. C., Montillo, A. A. and Bottiglieri, T. (2022). “Targeted Metabolomic Analysis in Alzheimer’s Disease Plasma and Brain Tissue in Non-Hispanic Whites.” J Alzheimers Dis.

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BACKGROUND: Metabolites are biological compounds reflecting the functional activity of organs and tissues. Understanding metabolic changes in Alzheimer’s disease (AD) can provide insight into potential risk factors in this multifactorial disease and suggest new intervention strategies or improve non-invasive diagnosis. OBJECTIVE: In this study, we searched for changes in AD metabolism in plasma and frontal brain cortex tissue samples and evaluated the performance of plasma measurements as biomarkers. METHODS: This is a case-control study with two tissue cohorts: 158 plasma samples (94 AD, 64 controls; Texas Alzheimer’s Research and Care Consortium – TARCC) and 71 postmortem cortex samples (35 AD, 36 controls; Banner Sun Health Research Institute brain bank). We performed targeted mass spectrometry analysis of 630 compounds (106 small molecules: UHPLC-MS/MS, 524 lipids: FIA-MS/MS) and 232 calculated metabolic indicators with a metabolomic kit (Biocrates MxP® Quant 500). RESULTS: We discovered disturbances (FDR≤0.05) in multiple metabolic pathways in AD in both cohorts including microbiome-related metabolites with pro-toxic changes, methylhistidine metabolism, polyamines, corticosteroids, omega-3 fatty acids, acylcarnitines, ceramides, and diglycerides. In AD, plasma reveals elevated triglycerides, and cortex shows altered amino acid metabolism. A cross-validated diagnostic prediction model from plasma achieves AUC = 82% (CI95 = 75-88%); for females specifically, AUC = 88% (CI95 = 80-95%). A reduced model using 20 features achieves AUC = 79% (CI95 = 71-85%); for females AUC = 84% (CI95 = 74-92%). CONCLUSION: Our findings support the involvement of gut environment in AD and encourage targeting multiple metabolic areas in the design of intervention strategies, including microbiome composition, hormonal balance, nutrients, and muscle homeostasis.

Johannesson, L., Wall, A. E., Bayer, J., McKenna, G. J., Rosenzweig, M., B, D. A. G., Koon, E. C. and Testa, G. (2022). “Robotic Donor Hysterectomy Results in Technical Success and Live Births After Uterus Transplantation: Subanalysis Within the Dallas Uterus Transplant Study (DUETS) Clinical Trial.” Clin Obstet Gynecol 65(1): 59-67.

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Minimally invasive procurement of uterine grafts for transplantation can decrease living donor recovery time. We examined recipient outcomes for grafts procured by robotic-assisted donor hysterectomies with transvaginal extraction in the Dallas UtErus Transplant Study (DUETS). All 5 grafts were successfully transplanted. Recipients had a median 4.5-hour surgical time, 0.25 L estimated blood loss, and 4-day hospital stay. Four recipients had grade III surgical complications and three had acute cellular rejection. At 18 months, graft viability was 100%, with an 80% live birth rate. This report demonstrates the feasibility and reproducible success of using uterus grafts from living donors who underwent robotic-assisted donor hysterectomy.

Johannesson, L. and Gregg, A. R. (2022). “Foreword: Uterine Transplantation in Pregnancy.” Clin Obstet Gynecol 65(1): 1-3.

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The title of our introduction lends itself to providing an understanding of how this special edition of uterus transplantation (UTx) came to be. UTx is an approach used to overcome what has for long been called the last hurdle of infertility, uterine factor infertility. The procedure has gained traction around the world following the earliest published successes from Sweden in 2014. In the United States, success was achieved first at Baylor University Medical Center in Dallas (BUMC) in 2017, followed by Cleveland Clinic and Hospital of the University of Pennsylvania. All 3 institutions initiated research protocols that are active today. The success of these programs recently has led to patient access to UTx off research protocols at BUMC and University of Alabama Medical Center.

Järvholm, S. and Warren, A. M. (2022). “Uterus Transplantation: Lessons Learned From a Psychological Perspective.” Clin Obstet Gynecol 65(1): 52-58.

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Uterus transplantation has gained increasing acceptance as a medically viable treatment to achieve pregnancy in women with absolute uterine infertility or loss of uterus. Over 20 live births have occurred worldwide since the first successful live birth in Sweden in 2014. However, the psychological and emotional impact on women who seek uterus transplant, their partners, and the women who donate their uterus is a critical area to explore. This paper will discuss issues related to recipient and donor selection, parenting posttransplant, and consideration of unanticipated outcomes including uterus transplant failure and inability to achieve pregnancy.

Hannon, V. N., Tinguely, P., McKenna, G. J., Brustia, R., Kaldas, F. M., Scatton, O., Spiro, M., Raptis, D. A., Busuttil, R. W. and Klintmalm, G. B. (2022). “New ERAS in liver transplantation – Past, present and next steps.” Clin Transplant: e14625.

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There are parallels between the history of enhanced recovery after surgery (ERAS) and liver transplantation. Both have been established and advanced by innovative individuals, often going against perceived wisdom and convention. Liver Transplantation has traditionally been considered too complex for ERAS pathways, despite a small number of trials showing them to be both safe and of benefit. To date, there are very few randomized controlled trials and cohort studies publishing outcomes on liver transplant patients enrolled in comprehensive ERAS pathways. To progress our field, the 2022 International Liver Transplantation Society’s Consensus Conference has created expert panels to analyze the evidence in 32 domains of the liver transplantation pathway using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach to generate expert recommendations. These recommendations will be voted on by the international community to gain consensus using the Danish model, and create the ERAS4OLT.org Enhanced Recovery after Liver Transplantation Pathway.