A Welcome from CEO Don Webber

The Fall 2024 Clinical Conferences provided another significant opportunity to showcase global research on the use of Hypothermic Oxygenated Perfusion (HOPE). Bridge to Life has recently returned from the 30th International Congress of The Transplantation Society (TTS 2024) in Istanbul, Turkey and the American College of Surgeons (ACS 2024) in San Francisco, California. As was the case with the Spring 2024 clinical conferences, both meetings contributed significantly to the dissemination of research and literature that advance innovation for transplant professionals and recipients. For Bridge to Life, these events provided additional major opportunities to present the latest data on Hypothermic Oxygenated Perfusion (HOPE), in conjunction with our VitaSmart™ Oxygenated Machine Perfusion System Machine technology. Here’s our news from TTS 2024: Three Italian studies on HOPE (Hypothermic Oxygenated Perfusion) in liver transplantation presented focused on the safety of HOPE, its effectiveness in improving outcomes in redo-liver transplantation, and its potential for evaluating biomarkers of liver viability.

“We continue to be impressed with the value that the use of HOPE brings to increasing the supply of available livers for transplantation, potentially improving access for those in need of livers and reducing waiting time for transplantation,” Dr Damiano Patrono, MD, Liver Transplant Unit, AOU Città della Salute e della Scienza di Torino, Italy

“Our academic research centre has been at the forefront of evaluating the impact of HOPE in several aspects of liver transplantation,” said Dr Damiano Patrono, MD, Liver Transplant Unit, AOU Città della Salute e della Scienza di Torino, Italy and principal investigator of the three trials. “We continue to be impressed with the value that the use of HOPE brings to increasing the supply of available livers for transplantation, potentially improving access for those in need of livers and reducing waiting time for transplantation,” he further commented.

Presentations included:

Outcomes of redo-liver transplantation using hypothermic oxygenated machine perfusion: a multicentre cohort study (REDO-HOPE), D. Patrono (General Surgery 2U – Liver Transplant Unit, AOU Città della Salute e della Scienza di Torino), et al

• Redo-liver transplantation (LT) is a challenging operation and is associated with an increased rate of postoperative complications and reduced graft and patient survival. Although optimal grafts are normally used for redo-LTs, these might not be readily available. By improving preservation and allowing prolonged preservation time, hypothermic oxygenated machine perfusion (HOPE) was shown to improve outcomes of redo-LT.
• REDO-HOPE is a multicentre cohort study aimed at investigating outcomes of redo-LT performed using grafts treated by HOPE. Adult (?18-year-old) recipients of a second or third liver transplant performed between January 2016 and December 2023 were included. Outcomes of HOPE redo-LT were compared with benchmark values and with those of a matched group of redo-LT performed using static cold storage. Primary endpoint of 12-month graft survival were met. According to this preliminary analysis, HOPE may allow performing redo-LT with outcomes comparable to benchmark values despite the use of extended criteria donors (ECD) grafts.

VIEW FULL ABSTRACT HERE

Hypothermic oxygenated machine perfusion is not associated with an increased risk of infection in the recipient: A retrospective single-centre cohort study S. Corcione (General Surgery 2U – Liver Transplant Unit, AOU Città della Salute e della Scienza di Torino), et al

• Use of machine perfusion (MP) in liver transplantation (LT) is gaining widespread acceptance. One potential drawback of MP is the risk of graft contamination due to the increased manipulation and exposure, determining infection in the recipient. Bacterial overgrowth resulting in severe recipient sepsis has been well documented during normothermic machine perfusion, but data on hypothermic oxygenated machine perfusion (HOPE) are scarce. Aim of this retrospective study was evaluating the risk of blood stream infection in recipient following HOPE versus static cold storage (SCS). Adult (?18-year-old) LT recipients transplanted in the period March 2016 – June 2023 were included.
• The rate of bloodstream infection after LT were comparable between study groups. Of note, patients in HOPE group presented more positive microbiological samples, mostly from bile or tracheal aspirates, not associated with clinical symptoms.

VIEW FULL ABSTRACT HERE

Circulating cell-free DNA in liver transplantation: A pre- and post-transplant biomarker of graft dysfunction, T. Carradori (General Surgery 2U – Liver Transplant Unit, AOU Città della Salute e della Scienza di Torino), et al

• Reliable biomarkers are needed to assess graft dysfunction after liver transplantation (LT) and facilitate graft monitoring. This study investigated cell-free DNA cfDNA) as a pre-and post-LT marker of graft dysfunction.
• Donor-derived cfDNA (dd-cfDNA) levels were determined at fixed timepoints in 45 consecutive LT recipients (baseline, from day 0 to day 7, week 2-3-4, 3 and 6 months). 22 (49%) patients received a graft treated by hypothermic oxygenated machine perfusion (HOPE) and 3 (7%) by normothermic machine perfusion. Perfusate levels of cfDNA and mitochondrial cfDNA (mt-cfDNA) were available for 20 recipients of a HOPE-treated graft. cfDNA and mt-cfDNA were correlated to other parameters of graft function and clinical outcome.
• In LT, dd-cfDNA correlates with hepatocyte necrosis and represents an aspecific yet sensible marker of graft dysfunction. When HOPE is used, perfusate mt-cfDNA correlates with liver injury and function after LT and may represent a further tool of liver viability assessment.

VIEW FULL ABSTRACT HERE

These results, along with data from other HOPE studies conducted in Europe, continue to collectively validate the safety and effectiveness of HOPE. Here’s our news from ACS 2024: Portuguese Transplant Center Analysis of First 100 Cases of Hypothermic Oxygenated Perfusion (HOPE) in Liver Transplantation Demonstrates Increased Use of Marginal Grafts, Making More Livers Available for Transplantation An analysis of 100 cases of liver transplantations at a Portuguese Transplant Center demonstrates that the use of Hypothermic Oxygenated Perfusion (HOPE) has the potential to lower the incidence of complications and maximizes the use of donor organs with extended criteria. “In our analysis, HOPE increased the use of marginal grafts and provided good function of the grafts in the immediate postoperative period…” Maria João Amaral, General Surgery Department – Unidade Local de Saúde de Coimbra, Portugal “In our analysis, HOPE increased the use of marginal grafts and provided good function of the grafts in the immediate postoperative period,” said Maria João Amaral, General Surgery Department – Unidade Local de Saúde de Coimbra, Portugal and principal investigator of the analysis. “In addition, there was a decrease in the non-anastomotic strictures (NAS) rate in our Center,” she added. The analysis was conducted using data collected between August 2020 and July 2023, from 100 cases of liver transplants efficiently using HOPE. Data were analyzed from the donor, graft and recipient, and from the intra and postoperative period. The development of non-anastomotic strictures (NAS) was also analyzed after excluding patients with arterial complications and biliary cast syndrome. NAS incidence was 6.98% (N=86) and 7.69% for cases with follow-up >6 months (N=65) (previously estimated at 16.9% at the Coimbra Transplant Center).

The Value of Strong Collaboration Between Academic Research Centers and the Transplantation Industry

Bridge to Life and ULS Coimbra announced a new formal collaboration to enhance the preservation of livers awaiting transplantation. The unique partnership in the field of organ transplantation marks a milestone in the development of working relationships between academic research institutions and the biomedical and medical technology industries. The partnership includes development of video case studies to raise awareness of breakthrough procedures at Unidade de Transplantação Hepática de Adultos, Unidade Local de Saude de Coimbra, Coimbra, Portugal. The collaboration was announced in conjunction with the 32nd anniversary of ULS Coimbra’s liver transplant program. The initiative kicks off with the development and launch of a case study demonstrating the important organ transplantation research and procedures being conducted at ULS Coimbra.

ULS Coimbra is one of the largest hospitals in Portugal with a legacy of innovation in organ transplantation. ULS Coimbra fosters a comprehensive research, teaching and patient-centered care approach. ULS Coimbra’s main mission is to deliver high-quality clinical care in a context of pre and postgraduate training with a strong focus on research, scientific knowledge and innovation. The hospital offers comprehensive care across all the leading medical and surgical specialties. ULS Coimbra´s centers of excellence ensure high standard healthcare services in specialized areas such as human organ transplantation. It is a medical institution in Portugal recognized by its highly qualified reference centers in medical and surgical specialized areas. ULS Coimbra has modern laboratory and storage facilities, holding specialized equipment and human resources for biological and tissue sample characterization. ULS Coimbra represents an important part of Coimbra Health Ecosystem and is a member of the collaborative network M8 Alliance of Academic Health Centers, Universities and National Academies known for their educational and research excellence. “Bridge to Life is excited to support the innovations and advancements in organ transplantation at ULS Coimbra and look forward to combining our expertise and experience with the significant legacy of ULS Coimbra in organ transplantation,” said Mauricio Carvalho, Director of Medical & Scientific Affairs. “While academic research and industry have collaborated in other fields, this marks the first time that such an initiative is taking place in the field of organ transplantation,” he further commented.

Transplantation in the News

Normothermic Regional Perfusion (NRP) NPR covered an organ retrieval procedure that remains scarcely used in the U.S. In the article and radio piece titled “Doctors Try a Controversial Technique to Reduce the Transplant Organ Shortage,” NPR discussed the use of normothermic regional perfusion (NRP) to recover a liver and two kidneys by Dr. Marty Sellers of Tennessee Donor Services. While NPR labeled the procedure as “controversial,” Dr. Sellers described it as “revolutionary.” So, what exactly is NRP? Although it is not yet widely adopted in the U.S., NRP was first used in Spain in 2002 and is currently employed in several European countries, including France, the Netherlands, and the UK. In Italy, NRP is mandated as the only method for organ recovery following circulatory death (DCD), as it provides additional time to assess the viability of organs for transplantation. To address potential ethical concerns-dubbed “the controversy” by NPR-most countries, including the U.S., require surgeons to wait five minutes before initiating organ retrieval. The ethical question revolves around restarting circulation after the patient has been declared dead due to circulatory cessation. This raises concerns about inadvertently reactivating brain neurons and when exactly the patient is considered “officially” dead. For example, in Italy, the mandated waiting time is 20 minutes. During this waiting period, organs lose viability with every passing second without circulating blood, and much can happen in those 5 to 20 minutes of “no-touch” time. Dr. Sellers’ use of the term “revolutionary” reflects the belief that, while NRP is still limited in the U.S., it has the potential to increase the number of available organs for transplantation, benefitting many patients on the waiting list. NRP allows more time to evaluate organ quality and provides a broader window for organ allocation. This extended time could lead to a higher utilization rate of organs, thus reducing the waitlist. The transplant community largely supports expanding the use of NRP for DCD organs over Standard Rapid Recovery (SRR), but it’s important to recognize NRP’s limitations. During NRP, in situ perfusion is typically conducted using an Extracorporeal Membrane Oxygenation (ECMO) system. However, once the NRP procedure is complete, the organ is transported either under perfusion without oxygen (ischemic perfusion) or in Standard Cold Storage to the recipient center. Both approaches do not completely mitigate the negative effects arising from the lack of oxygen. This is where Hypothermic Oxygenated Perfusion (HOPE) comes into play. HOPE cools the organs to temperatures between 4 and 12°C, dramatically lowering their metabolic rate to roughly 10% of normal. The system also delivers oxygenated perfusion to the dormant organ as it awaits transplantation. This oxygen-rich environment revitalizes the mitochondria-the cell’s powerhouse-priming the cells before transplantation and potentially lowering the risk of reperfusion injury, a major contributor to post-transplant complications. So, what’s the takeaway on NRP? While NRP shows great promise, it is not sufficient on its own to ensure optimal organ viability when the risk profile of the organ increases. The combination of abdominal NRP with end ischemic HOPE may provide the best chance for preserving organ quality during transport and transplantation. Together, these techniques could offer a synergistic approach to improving transplant outcomes.

References

Pr. Corinne Antoine, et al, Direction Générale Médicale et Scientifique, Agence de la biomédecine, Saint Denis, France; Liver Transplantation from Controlled Donors after Circulatory Death using Normothermic Regional Perfusion: Initial Experience of the French Protocol; Liver Transplantation, Volume 6, Issue 11, November 2020.

Riccardo De Carlis, MD, et al, Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; How to preserve liver grafts from circulatory death with long warm ischemia? A retrospective Italian cohort study with normothermic regional perfusion and hypothermic oxygenated perfusion; Transplantation, Volume 105, Issue 11, November 2021.

Amelia J. Hessheimer, et al, General & Digestive Surgery, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain; General & Digestive Surgery Service, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, Barcelona, Spain; IDIBAPS, CIBERehd, University of Barcelona, Spain; Abdominal Normothermic Regional Perfusion in DCD Transplantation: And Risk for Loss; American Journal of Transplantation, Volume 22, Issue 4, April 2022.

Xavier Muller, MD, et al, Department of Surgery and Liver Transplantation, Croix-Rousse University Hospital, University of Lyon I, Lyon, France; Hypothermic Oxygenated Perfusion Versus Normothermic Regional Perfusion in Liver Transplantation From Controlled Donation After Circulatory Death; Annals of Surgery, Volume 272, Number 5, November 2020.

New York State Reaches Organ Donation Milestone More than half of eligible New York State residents have signed up to be organ donors, according to a story in The New York Times. The state’s health commissioner, while pleased, said that is still not enough. Bridge to Life is always encouraged to see the supply of organs available for transplantation increased. However, it is critical to address the need to more effectively preserve those organs so they can be appropriate candidates for transplantation. That is why Bridge to Life is committed to advancing our research with Hypothermic Oxygenated PErfusion (HOPE) with the VitaSmart™ Oxygenated Machine Perfusion System. Bridge to Life is currently in the final stages of evaluating the 1-year follow-up results from our pivotal, multicenter, randomized HOPE clinical trial in the U.S. We look forward to expanding access to this innovative technology for U.S. transplant centers, organ procurement organizations, and, most importantly, patients waiting for viable livers. Bridge to Life anticipates submitting its FDA approval application by Q1 2025.

Bridge to Life and the Arts: The Many Ways that Bridge to Life Supports the Transplantation Community

Fifteen years ago, Aaron Gilchrist, Bridge to Life Vice President of Sales, North America, serendipitously discovered the value of artistic expression to communicate the transplantation experience from the eyes of artists personally impacted by organ transplantation. Here is Aaron’s very personal journey to discover that there are myriad ways to help transplantation patients: It all started in 2009, when Bridge to Life joined the Organ Procurement and Transplant Community with the introduction of our Belzer UW® line of organ preservation products. When preparing for our first conference, which was AOPO 2009, in St. Louis, we talked about how we might make a splash as we were introducing Bridge to Life to the Transplant Community for the very first time. I attended so many years prior, where a company by the name of St. Gobain displayed cans of Playdough for creative use by the conference attendees. Medical Device Engineers at this conference made delightful works of art displayed at the booth. Two weeks later, when I was at my desk, I received a box in the mail. What was in it? A can of Playdough. That sparked an idea: What if Bridge to Life could inspire a creative outlet for expressing the organ transplantation experience while making a memory for those whom we wanted to meet? As a result, we took the risk – even though there were some who were reluctant – and I reached out to artists in the St. Louis area.

“What if Bridge to Life could inspire a creative outlet for expressing the organ transplantation experience while making a memory for those whom we wanted to meet?” Aaron Gilchrist, Vice President of Sales, North America

Serendipity Having narrowed down the list via Google search, I landed on an artist by the name of Marlene Lewis. Her artwork was rich and full of color, and in my top 2 favorites found in my search. But nothing could have prepared me for our first phone call. I explained to Marlene that I had found her on the internet and was interested to commission a piece of artwork in the coming weeks. She thought that it was fast, and wisely asked what the piece was meant for. I responded by saying it was for organ donation. Then the phone went silent. After a few moments, I asked – “I am sorry – did I say something?” Marlene said, “No – it’s just…It’s just my sister had a heart-lung transplant and received 7 years from her gift of life. Needless to say, I was on the next plane to St. Louis. In a world of disbelief, I found myself 24 hours later, sitting in a studio full of artwork, with an old comfortable sofa in the middle, sitting next to a golden retriever. Marlene’s studio was full of beautiful pieces, ranging from plein air to abstract nudes. There was a liveliness to her work and so much color. We sat down together and talked about her experience – her sister. Then (and many times since) we have discussed the journey of not just the organs, but the donor families and the recipients. This led us to the concept of the “Heart of Hope”, which Marlene painted for the conference. Having such a serendipitous introduction, we thought, what could be better than to have Marlene there to present her artwork. Then, thinking back to the Playdough, we did one thing more – we fingerpainted hand-painted heart tiles at the conference on clear Lucite. I am pretty sure people left wondering, who are these guys at Bridge to Life? But we made a first impression – one that has lasted. Art Takes Flight Since that first AOPO meeting, the original Heart of Hope, and the art program Art, Hearts and Hope, has had quite an extraordinary journey, and it seems that this wonderful work of art truly had a life of its own, through its beauty and ability to keep on giving. It was such a hit, in fact, that we knew we needed to create a new piece every time we came to this conference. This became an annual tradition and led to the creation of the 2010 piece, an abstract hourglass one way, and a butterfly when rotated – and subsequent pieces such as Hope Renewed and Seeds of Hope – an abstract tree with heart shaped leaves that fall to the ground and sprout new ones (this is one of my favorites). Each year, Bridge to Life conducted give-away raffles at AOPO, created holiday cards with our art, and loaned our commissioned art to organizations wishing to display or reprint pieces. Beyond the transplant community, we have also used the artwork with Departments of Motor Vehicles and schools, and even once created special “Have a Heart” QR code in the shape of a heart which could be scanned to register to become a donor. This made a very popular T-Shirt while registering people to donate!!! One special extension of this project has been our work with the One Legacy Donate Life Rose Parade Float, in a program called “Hearts for Heroes”. Each year transplant recipients and living donors ride with the Donate Life Float at the Rose Parade on New Year’s Day. Also honored on the float are those who donated at the time of their passing, whose images adorn the float as “floragraphs” or floral pictures. For the last 13 years, we have worked collaboratively to honor those heroes with a specially painted heart tile, like the ones we painted at our first conference. Each one is painted individually, using different colors, and uniquely, in inverse. As the medium is a clear Lucite, the painted side comes through the other side, and the heart appears as if it is on the other side of a glass pane. They are powerful symbols – and each donor family gets to stop and find the one that reminds them most of their loved one. Hearts for Heroes has been presented to thousands of float riders, walkers and members of donor families, and has served to connect people on what seemed a very singular journey, to realize they are all connected. This continues to be a labor of love for the artist, Marlene. “Paintings are ultimately metaphors for our lives. Every shape and color can be seen as our mark in this world to see our dreams and wishes are realized. And, like life, painting is a process of exploration,” expressed Marlene. “I never tire of it because I’m always looking to see what comes next,” she added. “Creating paintings for Bridge to Life has given me the chance to give back to those individuals and families involved in viable organ donation,” Marlene continued. “Having had a sister who received a heart-lung transplant and seeing a new life of hope unfold for her, I was humbled and thrilled at the idea of creating works of art for those individuals involved in this struggle.” More recently, Bridge to Life expanded the program and connected with a new artist Niki Litts, a multi-media artist trained at the Academy of Fine Arts in Philadelphia – and a recipient of a transplanted liver at age 12. When I first met Niki, I instinctively knew that her passion for expressing herself – and her liver transplant experience – through fiber arts and ceramics would be the ideal complement to the stunning artwork created by Marlene. Niki was excited to participate with Bridge to Life because, as she put it, “It is hard to find a community to be a part of if you don’t know other transplant recipients.” Niki’s first piece was a little girl – something of a self-portrait – with her arm outstretched toward two hearts, representing her journey over 30 years ago to receive her liver transplant. Her second piece included a mother hugging a child and a child starburst, with concentric circle dots representing different organs. This piece was aimed at the donation experience, and the grief of losing a loved one, while starting hopes and dreams for those in need of a heroic organ donation. “My art provides an opportunity to express my feelings – feelings that resonate with the transplant community,” shared Niki. “I am grateful to Bridge to Life for providing this outlet for me. I would do this for the rest of my life.” As our wonderful and empowered artists have demonstrated, a true metamorphosis occurs when a person is given a second chance at life. One of the most important issues is the significant number of people waiting for a life-saving transplant, and the feeling of helplessness resulting from the lack of available viable organs. Bridge to Life – through our ongoing research and collaborations with academic researchers – is at the forefront of making more organs available for transplantation. Bridge to Life wishes to thank everyone who has played a role in this inspirational project. It is our “Hope” that this program will continue to bring joy and love to the Transplant Community we are so proud to support.