Research Spotlight

Lanfear, A. T., M. Hamandi, J. Fan, J. M. DiMaio and T. J. George (2019). “Trends in HeartMate 3: What we know so far.” J Card Surg Nov 6. [Epub ahead of print].

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BACKGROUND: The HeartMate 3 left ventricular assist device (LVAD) is a novel, intrapericardial, centrifugal-flow pump with a fully magnetically-levitated rotor designed to provide hemodynamic support in patients with end-stage heart failure. Unique aspects of this LVAD have allowed for improved hemocompatibility and the development of minimally-invasive implantation techniques. METHODS: The PubMed, EMBASE, and Google Scholar databases were searched for publications relating to the HeartMate 3 device, with a focus on hemocompatibility related outcomes, anticoagulation management, and surgical techniques. RESULTS: Nine articles analyzing hemocompatibility related outcomes from two clinical trials, two clinical studies, and one registry series were identified. CONCLUSION: HeartMate 3 has reduced the rate of disabling stroke and pump thrombosis. However, despite increased hemocompatibility due to specialized design features, the residual risk of both surgical, and gastrointestinal bleeding remains a major adverse outcome. Different anticoagulation management and surgical techniques have been evaluated to address the remaining complications.

Kumano, K., M. C. Lawrence, N. Onaca, M. F. Levy and B. Naziruddin (2019). “Successful allogeneic islet transplantation after total pancreatectomy with islet autotransplantation to restore normoglycemia: a case report.” Acta Diabetol Nov 26. [Epub ahead of print].

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Total pancreatectomy with islet autotransplantation (TPIAT) has been recognized as a treatment option for patients with refractory chronic pancreatitis (CP) who experience debilitating pain and impaired quality of life. Restoring as much endocrine function as possible is crucial to prevent postsurgical diabetes and reduce the risk of brittle diabetes and hypoglycemic unawareness. However, obtaining sufficient islet yield from CP pancreata remains a technical challenge due to chronic inflammation, which damages the morphology of the pancreas. A previous report showed that approximately 20% of TPIAT patients receive a low islet yield (< 2500 IEQ/kg), and those patients have poor metabolic outcomes compared to patients who receive a high islet yield (> 5000 IEQ/kg). Therefore, salvage therapy is considered for CP patients who develop postsurgical brittle diabetes. Whole-pancreas allogeneic transplantation after TP has been reported to restore both endocrine function and exocrine function. To date, there has been one case report of islet allogeneic transplantation after TP in acute pancreatitis, as islet allogeneic transplantation has largely been restricted to type 1 diabetic patients with severe hypoglycemia and glycemic lability. Thus, it remains unknown if islet allogeneic transplantation could be used as salvage therapy to restore endocrine function after TPIAT following islet graft dysfunction. Here, we report a novel case of allogeneic islet transplantation in a CP patient who had postsurgical diabetes and multiple episodes of hypoglycemic unawareness after TPIAT. (Excerpt from text, p. 1; no abstract available.)

Kristek, J., L. Johannesson, G. Testa, R. Chmel, M. Olausson, N. Kvarnstrom, N. Karydis and J. Fronek (2019). “Limited Availability of Deceased Uterus Donors: A Transatlantic Perspective.” Transplantation 103(12): 2449-2452.

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Women with absolute uterine-factor infertility (AUFI) had until recently only the opportunity to have children through adoption, foster parenting, or gestational surrogacy. However, for some women with AUFI, none of these options is possible because of religious, societal, personal, or other reasons. Uterus transplantation (UTx) has recently been introduced as a unique opportunity for both genetic and gestational motherhood. To date, most UTx were accomplished with uterus transplants procured from living donors. Although deceased donor (DD) UTx have been performed successfully, the overall experience remains rare. Notably, most (10/13) DD UTx have been performed by the teams in Dallas, TX and Prague, Czech Republic. Recently, the first baby was born to a recipient after DD UTx in São Paulo, demonstrating proof of concept for DD UTx. DD UTx is desirable, as it avoids risks associated with complex live donor hysterectomies and (2) not every patient in need may have a qualifying living donor available. Thus, it appears critical to analyze the potential of DD UTx. Several unknowns and limitations to this pursuit need to be addressed and include (1) the lack of standardized evaluation criteria of uterus DD (both standard and extended criteria), (2) information on the availability of potential uterus DDs, (3) assuring that potential donors will be identified by organ procurement organizations (OPOs), and (4) issues of consent beyond that taken for the procurement of solid organs for transplantation. Here, we address those issues in a transatlantic approach with an analysis in the Czech Republic, Sweden, the United Kingdom, and the United States. We aimed to roughly approximate the volume of potential uterus donors, demand for transplantation linked to geographical region. Moreover, we suggest criteria allowing OPOs to identify uterus DD and introduce the experience at our institutions on getting consent. (Excerpt from text, p. 2449; no abstract available.)

Kataria, V., L. Moore, S. Harrison, O. Hernandez, N. Vaughan and G. Schwartz (2019). “Evaluation of Serotonin Release Assay and Enzyme-Linked Immunosorbent Assay Optical Density Thresholds for Heparin-Induced Thrombocytopenia in Patients on Extracorporeal Membrane Oxygenation.” Crit Care Med Nov 27. [Epub ahead of print].

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OBJECTIVES: Heparin-induced thrombocytopenia is a recognized concern in patients on extracorporeal life support. The purpose of this study was to evaluate the applicability of an enzyme-linked immunosorbent assay optical density threshold less than 1 to rule out heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation. DESIGN: Retrospective, single-center study. SETTING: Patients were recruited from a prospectively maintained database of all patients on extracorporeal membrane oxygenation from 2012 to 2018 at a tertiary referral center. PATIENTS: Forty-seven patients on extracorporeal membrane oxygenation support. INTERVENTIONS: The primary objective was to evaluate the application of enzyme-linked immunosorbent assay optical density thresholds and the serotonin release assay in patients on extracorporeal membrane oxygenation. Patients were divided into two cohorts, serotonin release assay negative and serotonin release assay positive. In order to perform a sensitivity and specificity analysis of enzyme-linked immunosorbent assay optical density thresholds, heparin-induced thrombocytopenia negative was defined as an optical density less than 1.0 and heparin-induced thrombocytopenia positive as an optical density greater than or equal to 1.0. MEASUREMENTS AND MAIN RESULTS: Utilizing the prespecified optical density thresholds, a specificity and negative predictive value of 89% and 95% were achieved, respectively. CONCLUSIONS: This assessment has helped to identify optical density thresholds for patients undergoing extracorporeal membrane oxygenation. Our data suggest that an optical density threshold of 1.0 may aid clinicians in objectively ruling out heparin-induced thrombocytopenia without sending a confirmatory serotonin release assay. Increasing the optical density threshold to 1.0 resulted in a high specificity and negative predictive value.

Jadavji, N. M., H. Mosnier, E. Kelly, K. Lawrence, S. Cruickshank, S. Stacey, A. McCall, S. Dhatt, E. Arning, T. Bottiglieri and P. D. Smith (2019). “One-carbon metabolism supplementation improves outcome after stroke in aged male MTHFR-deficient mice.” Neurobiol Dis Dec 1. 132:104613.

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The prevalence of stroke increases with age and the ability to absorb all nutrients from our diets decreases with age. Nutrition is a modifiable risk factor for stroke, which is a leading cause of death and disability in world-wide. Deficiencies in onecarbon metabolism, including in methyltetrahydrofolate reductase (MTHFR), have been linked to increased risk of stroke. The Mthfr(+/-) mice mouse model mimic the phenotype of the MTHFR677CT polymorphism, such as elevated levels of homocystine. Using this mouse model, the aim of this study was to investigate the impact of dietary supplementation with 5-methylTHF, vitamin B12, and choline after ischemic stroke. Male Mthfr(+/-) and wildtype littermate control mice were aged (~1.5-year-old) and were placed on control diet (CD) 4-weeks prior to sensorimotor cortex damage using photothrombosis (PT), a model for ischemic stroke. Post-operatively, one group of Mthfr(+/-) and wildtype littermate mice were placed on 5-methylTHF, vitamin B12, and choline supplemented diet (SD). Four weeks after PT and SD motor function was assessed using the accelerating rotarod, forepaw asymmetry, and ladder beam walking tasks. Total homocysteine and cysteine levels were measured in blood. Brain tissue was processed to assess lesion volume and investigate biochemical and molecular changes. After PT and SD, Mthfr(+/-) mice were able to stay on the accelerating rotarod longer and used their impaired forepaw to explore more when compared to CD animals. Furthermore, total homocysteine levels in plasma and lesion volume were reduced in Mthfr(+/+) and Mthfr(+/-) SD mice. Within the damage site, there were reduced levels of apoptotic cell death and increased neuroprotective cellular response in the brains of SD treated Mthfr(+/-) mice. This study reveals a critical role for onecarbon supplementation, with 5-methylTHF, vitamin B12, and choline, in supporting improvement after ischemic stroke damage.