Synthesis of Ti-Al-xNb Ternary Alloys via Laser-Engineered Net Shaping for Biomedical Application: Densification, Electrochemical and Mechanical Properties Studies

The lives of many people around the world are impaired and shortened mostly by cardiovascular diseases (CVD). Despite the fact that medical interventions and surgical heart transplants may improve the lives of patients suffering from cardiovascular disease, the cost of treatments and securing a perfect donor are aspects that compel patients to consider cheaper and less invasive therapies. The use of synthetic biomaterials such as titanium-based implants are an alternative for cardiac repair and regeneration. In this work, an in situ development of Ti-Al-xNb alloys were synthesized via laser additive manufacturing for biomedical application. The effect of Nb composition on Ti-Al was investigated. The microstructural evolution was characterized using a scanning electron microscope (SEM) equipped with energy dispersive spectroscopy (EDS). A potentiodynamic polarization technique was utilized to investigate the corrosion behavior of TiAl-Nb in 3.5% NaCl. The microhardness and corrosion behaviour of the synthesized Ti-Al-Nb alloys were found to be dependent on laser-processing parameters. The microhardness performance of the samples increased with an increase in the Nb feed rate to the Ti-Al alloy system. Maximum microhardness of 699.8 HVN was evident at 0.061 g/min while at 0.041 g/min the microhardness was 515.8 HVN at Nb gas carrier of 1L/min, respectively.

Failing Heart Transplants and Rejection—A Cellular Perspective

The median survival of patients with heart transplants is relatively limited, implying one of the most relevant questions in the field—how to expand the lifespan of a heart allograft? Despite optimal transplantation conditions, we do not anticipate a rise in long-term patient survival in near future. In order to develop novel strategies for patient monitoring and specific therapies, it is critical to understand the underlying pathological mechanisms at cellular and molecular levels. These events are driven by innate immune response and allorecognition driven inflammation, which controls both tissue damage and repair in a spatiotemporal context. In addition to immune cells, also structural cells of the heart participate in this process. Novel single cell methods have opened new avenues for understanding the dynamics driving the events leading to allograft failure. Here, we review current knowledge on the cellular composition of a normal heart, and cellular mechanisms of ischemia-reperfusion injury (IRI), acute rejection and cardiac allograft vasculopathy (CAV) in the transplanted hearts. We highlight gaps in current knowledge and suggest future directions, in order to improve cellular and molecular understanding of failing heart allografts.

Outcomes of diabetic patients with end-stage heart failure listed for heart transplantation: a propensity-matched analysis

Background There are on-going concerns about offering heart transplants to patients with diabetes due to the risk of poor outcomes. We investigated the current trends and outcomes of patients listed for heart transplants in the U.S. and provided a method for risk-stratification. Methods Using data from the United Network for Organ Sharing (UNOS), we identified heart failure patients listed for heart transplants between 2010 and 2019. Diabetic patients were propensity-matched with non-diabetes, and waitlist mortality as well as post-transplant graft survival were compared between the two matched groups. Further risk-stratification of the diabetic cohort was done based on the risk factors that independently predict the risk of graft failure. Results 28,928 adult patients (30% diabetic) with end-stage heart failure were added to the waitlist over the study period. In the propensity-matched cohort, waitlist mortality was higher with diabetics compared to non-diabetics: 19.3 vs 17.1 deaths per 100 person-years, respectively, (HR=1.13 (95% CI=1.04–1.22, p=0.002). Over the study period, 5739 diabetics (mean age 57.6 years, 21.9% female) were transplanted. A total of 1308 (23.3%) and 1143 (20.4%) graft failures occurred in diabetic and non-diabetic recipients, respectively. Compared to non-diabetics, diabetics experienced worse graft survival (HR=1.17, 95% CI=1.08–1.26, p<0.001). We developed a risk score based on the 12 risk factors/markers that independently predict worse graft survival and a risk score of 4 reasonably differentiates between low and high-risk diabetics. Low risk diabetics (score≤4) had similar graft survival as non-diabetics with 1- and 5-year survival of 92.7% and 80.5%, respectively, (HR=0.91, 95% CI=0.82–1.01, p=0.06). On the other hand, high-risk diabetics had worse graft survival compared to non-diabetics (HR=1.52, 95% CI=1.38–1.67, P<0.001) with 1- and 5-year graft survival of 86.8% and 69.8%, respectively. Conclusion Diabetic patients with end-stage heart failure listed for heart transplantation experience higher waitlist mortality and worse post-transplant graft survival compared to non-diabetics. However, a simple risk score can be used for further risk-stratification in these patients to maximize survival benefit. FUNDunding Acknowledgement Type of funding sources: None.

Twenty-year temporal and regional trends in heart transplantation in Europe: results from the Global Observatory on Donation and Transplantation (GODT)

Introduction Heart transplant (HT) remains the only cure for patients with advanced heart failure. However, limited supply of donors continues to be the main obstacle to growing transplant programs around the world. Since population changes are not uniform, describing temporal trends in availability of donors and in number of transplanted hearts will provide better understanding of regional variations in organ availability and allocation. Purpose We aim to evaluate temporal and regional trends in number of brain-dead donors (BDDs) and its association with the number of heart transplants (HTs) in Europe between 2000 and 2019. Methods Global Observatory on Donation and Transplantation (GODT) represents the world's most comprehensive source of data on organ donation and transplantation. Available data were collected for all European countries for the years (2000–2019) except for the year 2005. Geographical classification (north, west, central, south) was made according to EuroVoc definition. Trends of HTs and BDDs were assessed using Joinpoint Software of the National Cancer Institute to calculate the annual percentage change (APC) and reported as per million population (PMP). The linear correlation coefficient was assessed using R studio. Results Over the past two decades, there was a 35% increase in HTs PMP rate in Europe from the year 2000 to 2019 with an APC of 1.4% (95% CI [1.1–1.7], P<.0001). This change was more pronounced in Central Europe, where HTs PMP rate increased from 0.65 in 2000 to 2.93 in 2019 (APC 9.9% (95% CI [8.1–11.8], P<.0001)) and in Northern Europe, where HTs PMP rate increased from 2.97 in 2000 to 5.18 in 2019 (APC 2.7% (95% CI [1.8–3.7], P<.0001)) (Figure 1). Despite the increase in BDDs in Europe between 2000–2019 (from 3.62 to 12.25 donors PMP) (Figure 2), the association between increased BDDs and HTs varied between regions, with a very strong association in Central Europe (r=0.95, P<0.0001) and strong correlation in Northern Europe (r=0.64, P=0.003). However, positive correlation between BDDs and HTs was not seen in Southern or Western Europe (r=−0.52, p-value=0.02, r=0.02, p-value=0.94, respectively). Conclusion The number of BDDs has increased in Europe in the past two decades with a concomitant increase in HT volumes. A regional variation in the relationship between the number of BDDs and HTs was observed among European subregions, such that it was most pronounced in Central Europe. Understanding the reasons underlying these disparities can potentially inform improvement in organ allocation systems throughout Europe. FUNDunding Acknowledgement Type of funding sources: None.

PHENOMENON OF DEMIKHOV. At N.V. Sklifosovsky Institute (1960–1986). Paradigm shift in homologous organ transplantation: from overcoming biological incompatibility to artificial immunological tolerance (1960–1970)

The analysis of literature on experimental and clinical transplantation for the period of the 1968–1969 demonstrated that in the period from 1960 to 1970 the world transplantation saw a paradigm change in the field of homoorgan transplant: instead of overcoming the incompatibility between the donor organ and the recipient's body by using biological and physiological methods to influence the organ, which V.P. Demikhov had been dealing with for many years; surgeons and scientists, first abroad, and then in the USSR started developing and applying the creation of artificial immunological tolerance by using various physical, chemical and biological methods to impact recipient's body. The change of paradigms significantly influenced the implementation of organ transplantation techniques in clinic, including those of vital organs, and the further development of clinical transplantology. The data on the first heart transplants in 1968 and lung transplants in 1963–1970 have been presented.

Organ donation and transplantation in the Russian Federation in 2020 13th Report from the Registry of the Russian Transplant Society

Objective: to monitor the current trends and developments in organ donation and transplantation in the Russian Federation based on the 2020 data.Materials and methods. Heads of organ transplant centers were surveyed through questionnaires. Data control was done using the information accounting system of the Russian Ministry of Health. Between separate federal subjects of the Russian Federation and between transplantation centers, comparative analysis of data obtained over years was performed.Results. Based on data retrieved from the 2020 Registry, 44 kidney, 29 liver and 16 heart transplantation programs were functioning in the Russian Federation in 2020. The kidney transplant waitlist in 2020 included about 11.5% of the total 60,000 patients receiving dialysis. Organ donation activity in 2020 was 3.9 per million population, with a 74.6% multi-organ procurement rate and an average of 2.9 organs being procured from one effective donor. In 2020, there were 7.7 kidney transplants per million population, 3.8 liver transplants per million population and 1.7 heart transplants per million population. Same year, the number of transplant surgeries performed in the Russian Federation fell by 19.2% to 13.4 per million population against the background of the outbreak caused by the new coronavirus disease COVID-19. The city of Moscow and the Moscow region in 2020 accounted for 13 out of the 14 functioning organ transplantation centers, performing 66.3% of all kidney transplants and 72.4% of all extrarenal transplants in the country. The number of organ recipients in the Russian Federation have exceeded 130 per million population.Conclusion. In 2020, despite the new coronavirus disease COVID-19 pandemic and accompanying restrictive measures, transplant centers continued to perform organ transplants, run a waiting list and monitor organ recipients. However, the number of effective donors (–22.9%) and organ transplants (–19.2%) decreased, tentatively to the 2017 levels. In 2021, transplant centers with support from health authorities will have to restore the volume of transplant care with consideration to the real needs of the population and the donor resource. The COVID-19 factor, including vaccination of the population, as well as financial support to transplantation programs, will be decisive in shaping the trend of transplantation care and organ donation in the federal subjects of the Russian Federation in the coming 1–2 years.

Intoxicated Donors and Heart Transplant Outcomes: Long-Term Safety

Background: The opioid crisis has led to an increase in available donor hearts, although questions remain about the long-term outcomes associated with the use of these organs. Prior studies have relied on historical information without examining the toxicology results at the time of organ offer. The objectives of this study were to examine the long-term survival of heart transplants in the recent era, stratified by results of toxicological testing at the time of organ offer as well as comparing the toxicology at the time of donation with variables based on reported history. Methods: The United Network for Organ Sharing database was requested as well as the donor toxicology field. Between 2007 and 2017, 23 748 adult heart transplants were performed. United Network for Organ Sharing historical variables formed a United Network for Organ Sharing Toxicology Score and the measured toxicology results formed a Measured Toxicology Score. Survival was examined by the United Network for Organ Sharing Toxicology Score and Measured Toxicology Score, as well as Cox proportional hazards models incorporating a variety of risk factors. Results: The number and percent of donors with drug use has significantly increased over the study period ( P <0.0001). Cox proportional hazards modeling of survival including toxicological and historical data did not demonstrate differences in post-transplant mortality. Combinations of drugs identified by toxicology were not associated with differences in survival. Lower donor age and ischemic time were significantly positively associated with survival ( P <0.0001). Conclusions: Among donors accepted for transplantation, neither history nor toxicological evidence of drug use was associated with significant differences in survival. Increasing use of such donors may help alleviate the chronic donor shortage.