XPS™THE FLEXIBLE COMPREHENSIVE EVLP PLATFORM

*Humanitarian Device. Authorized by Federal law in the U.S for use in flushing and temporary continuous normother­mic machine perfusion of initially unacceptable excised donor lungs during which time the ex­vivo function of the lungs can be reassessed for transplantation. The effectiveness of this device for this use has not been demonstrated.

More than 70% of donorlungs worldwide aredeemed unusable and notused for transplantation.

Increase your lung donor pool with a fully flexible and comprehensive platform for EVLP

• Proven clinical protocol and extensive clinical practice• Developed with daily clinical challenges in mind• Based on expertise and experience from clinicians

First FDA approved device for EVLP

The XVIVO Perfusion System™ (XPS™) is CE­marked and FDA approved for ex vivo lung perfusion of initially unacceptable donated lungs*. The NOVEL Study in U.S was designed to establish the safety of the method.

The NOVEL Study – Establishing the safety of the method

The NOVEL study was the first prospective, multicenter clinical trial designed to evaluate the safety of Ex Vivo Lung Perfusion (EVLP) as a method to screen and identify good quality lungs that have been unused or rejected for transplantation.The one­year follow up of the study showed that EVLP with XPS™ and STEEN Solution™ is a safe tool to increase the percentage of transplanted lungs by screening the unused donor pool.

>70%

THE LUNG DONOR POOL

EXPANDING

Normothermic EVLP, ex vivo lung perfusion, is a technique to assess and evaluate donor lungs by providing optimal conditions of reperfusion and protective ventilation.

Normothermic EVLP attempts to simulate the in vivo environment of a donor lung using ventilation and perfusion of the isolated lung to assess and continuously evaluate lung function.

• Objective assessment of marginal/extended or DCD donor lungs

• More time to fully assess function and HLA match

• More time to choose optimal treatment strategy

• Opportunity to reassess prior to transplant

EVLP provides clinicians and transplant teams an ideal setting for donor lung evaluation and allows lung treatment:

The ultimate objective of EVLP is to expand the pool of transplantable organs and thus minimize mortality and morbidity on the transplant waiting list. More than 300 transplantations have been performed using this new unique technique. EVLP is not only the ideal setting for donor lung assessment and evaluation, it also opens up the possibility for future treatment of the lungs.

Increase your pool of transplantable organs with a fully flexible and comprehensive platform for EVLP, XVIVO Perfusion System (XPS™).

• XMAT™ ­ Remote monitoring system*• Barcode PGM calibration• Improved user interface• Integrated smart sequencing• Weight sensor

Introducing new features and upgrades!

XPS™ developed with daily clinical challenges in mind

The system was developed together with clinicians with genuine experience and knowledge fromnormothermic EVLP using STEEN Solution™. Understanding the clinical needs and challengestransplant teams encounter in daily work, the XPS™ facilitates the clinical decision making process and offers a flexible comprehensive platform for EVLP.

• Gives you control of the entire EVLP process

• Supported by clinical experience and knowledge

• All required EVLP components integrated

• X­ray and CT­scan possibilities

• In­line gas monitoring• Continuous data recording –

evaluate for safety and control

XPS™ – The first FDA HDE approved and clinically proven EVLP Technology on the market

*Currently not approved by the FDA.

• CardioHelp XVIVO Centrifugal Pump – Quadrox­iR next generation oxygenator

• Separate sterile area and perfusionist non­sterile area

• Heater/Cooler (15­39°C)• Hamilton ICU Ventilator• In­line gases (pO2, pH)

• Touchscreen user interface• Extract and analyse data• Configured to allow X­ray and

CT­scan of lungs• Integrated weight sensor platform

allowing measurement throughout the EVLP

Integrated system for innovative technique

• Adjustable to preferred clinical protocol

• Adjustable flow to preferred clinical protocol

• Adjustable ventilation

Flexibility

• Barcode scanning of PGM calibration data

• Integrated smart sequencing features

• Flexible and comprehensive platform for normothermic EVLP

Operational benefits on-site

• User remains in control as the EVLP process is performed on­site

• Continuous data recording – evaluate for safety and control

• User­friendly system

• Supported by clinical experience and knowledge

• X­ray and CT­scan possibilities

INTEGRATED SYSTEM FOR INNOVATIVE TECHNIQUE

STEEN Solution™ pump – Perfusate management system with integrated pumps to enable the addition, subtraction and recycling of STEEN Solution™ in the perfusion circuit. XPS™ is equipped with peristaltic pumps for convenient management.

XVIVO Monitoring and Analysis Tool™ – XMAT™* enables remote monitoring and analysis of integrated data captured during the EVLP procedure.

Platform for gas cylinders – one containing medical grade (100%) oxygen for membrane oxygenation and the other containing a mixture of medical grade gases (6% O2, 8% CO2, 86% N2) for membrane deoxygenation.

*Currently not approved by the FDA.

ICU­type Hamilton Ventilator withmodes designed to provide protectiveventilation of the ex vivo lung.

CardioHelp XVIVO centrifugal pump with integrated temperature and pressure sensors for monitoring of safety during the procedure.

The XPS™ is equipped with two in­line gas sensors, which enables real­time trending of pH and pO2 during EVLP.

XPS™ is specifically configured and designed for allowing X­ray and CT­scan while doing normothermic EVLP.

Thermoelectric heater/cooler device that uses water to maintain perfusate temperatures at any set point between 15–39°C.

Touchscreen computer display for the perfusionist and a display­only screen for the surgeon that displays data from the hardware components as well as trends important lung function parameters graphically.

AND UPGRADES INCLUDE THE FOLLOWING:

NEW FEATURE

• Added barcode scanner

for Perfusate Gas Monitor Calibration­ Improves usability and accuracy.

• Integrated smart sequencing feature to guide perfusionist through EVLP protocol and ventilation settings.

• Improved User Interface and Operation based on customer feedback.

Introduction of XMAT™ (XVIVO Monitoring and Analysis Tool™). Integrates data from XPS™, video cameras, bronchial scope images, x­ray images, ventilator information into single system for analysis and remote monitoring.

*Currently not approved by the FDA

EVLP COMPONENTS INTEGRATED

ALL REQUIRED

Allowing for standardization of EVLP

XPS™ was developed to provide transplantation teams with a consistent and easy­to­use method of performing EVLP in the hospital. The objective was to develop an automated perfusion system that would allow for standardization of EVLP, without interfering with the need for clinical flexibility. The donor lungs are transported in regular manner, in a cooler box from the procurement site. The donor lungs are flushed thoroughly with PERFADEX® or PERFADEX® Plus and then put on the EVLP platform. After warming up according to a detailed protocol, it is up to the EVLP team to set preferred ventilation and perfusion strategies depending on the requirements of each donor lung. Integrated in­line perfusate gas monitors (PGM™) enables for real­time trending of pH and pO2 during the entire EVLP procedure. The XPS™ also enables precise continuous monitoring of EVLP performance metrics, all pre­set by the EVLP team.

The XPS™ is intended to be used with STEEN Solution™ for flushing and temporary continuous normothermic perfusion of initially unacceptable excised donor lungs, during which time the function of the lungs can be evaluated and assessed as viable transplantable organ (FDA HDE approval August 2014).

XPS™ is a fully integrated off-the-shelf cardiac bypass system that includes all components needed to safely run normothermic EVLP. The XPS™ system is based on innovative technology from leading companies and includes a centrifugal pump (MAQUET CardioHelp), Hirtz heater/cooler and ICU-ventilator (Hamilton).

The XVIVO Perfusion System (XPS™) is intended for flushing and temporary continuous normothermic machine perfusion of isolated lungs, during which time the function of the lungs can be assessed for transplantation (for all other countries).

READ MORE ON XVIVOPERFUSION.COM

• New and improved

touchscreen monitor. Improved screen sensitivity. Upgraded operating system and improved communication links.

XVIVO MONITORING AND ANALYSIS TOOL XMAT™*

Video cameras

Bronchial scope images

Ventilator information

X-ray images

CENTERS WORLDWIDE

XPS™

Supporting data – clinically proven

The use of EVLP has after extensive experimental research been successfully transformed into clinical practice. Published reports from several centers show favorable clinical outcomes and clinical trials confirm these results.

Good interim results presented – The NOVEL study

The NOVEL study was the first prospective, multicenter clinical trial designed to evaluate the safety of Ex Vivo Lung Perfusion (EVLP) as a method to screen and identify good quality grafts from lungs that have been unused or rejected for transplantation. The participating centers in the NOVEL study used PERFADEX®, STEEN Solution™ and the XPS™ system to evaluate and assess rejected donor lungs.The one­year follow up of the study showed that EVLP with XPS™ and STEEN Solution™ is a safe diagnostic tool to increase the percentage of transplanted lungs by screening the unused donor pool.

X-ray possibilities

XPS™ is specifically designed to facilitate X­ray while performing normothermic EVLP. If a mobile X­ray unit is not available, XPS™ may be transported at shorter distances within the hospital as it has a battery built­in that could support up to 20 min. This allows for simultaneous X­ray without interrupting the EVLP process.

Continuous data recording – evaluate for safety and control

The touch­display monitors and software allows monitoring the procedure and components as well as data capturing. The software captures and displays key performance data in real time. Parameters displayed are PVR, delta pO2 etc. Data can easily be downloaded via an USB port.

In-line perfusate gas monitors (XVIVO PGM Disposable Sensors™) for real-time trending

The XPS™ is equipped with two in­line gas sensors, which enables real­time trending of pH and pO2 during EVLP.

XPS IN THE U.S

CONVENIENT, RELIABLE, STERILE

ACCESSORIES

The XPS Disposable Lung Kit™ contains specially developed disposables and pre-packed products to suit your needs and requirement for sterility. The products in our disposable kit have been carefully produced and selected - packaged and sterilized for your convenience.

Selected from leading suppliers

In-line gas monitoring the easy way

XVIVO PGM Disposable Sensors™ provides in­line, easily calibrated trending of the perfusate. The sensors are single­use, disposable in­line sensors intended to be used with the XPS™ to trend the pH and dissolved pO2 gases in STEEN Solution™ during ex vivo assessment and evaluation.The XVIVO PGM Disposable Sensors™ come pre­calibrated to STEEN Solution™ directly out of the package.

Clinically proven solution

STEEN Solution™ is a buffered extracellular solution that includes human albumin to provide an optimal oncotic pressure, and Dextran 40 to coat and protect the endothelium from excessive leucocyte interaction. STEEN Solution™ is designed to facilitate prolonged evaluation and promote stability of isolated lungs ex vivo.XVIVO Organ Chamber™ is a single­use, sterile disposable container designed to aseptically hold the lungs during the procedure.

*Humanitarian Device. Authorized by Federal law in the U.S for use in flushing and temporary continuous normothermic machine perfusion of initially unacceptable excised donor lungs during which time the ex­vivo function of the lungs can be reassessed for transplantation. The effectiveness of this device for this use has not been demonstrated.

The pre­packed kit contains all the necessary perfusion products and provides the aseptic interface between the XPS™ and the ex vivo lung. The sterile circuit includes Quadrox iR integrated centrifugal pump head/oxygenator and heat exchange membrane, pediatric hard­shell reservoir, Pall leucocyte filter, tubing and priming loop, gas sensor quick connectors and a 500 ml soft drain reservoir.

Other components included in the pre­packed kit are; pressure sensor line, fluid level sensor, cannulas, bacterial/ viral filter, ventilator flowsensor, Coaxial breathing circuit with flow sensor and sterile drape.

Convenient to order and easy to connect

The pre­packed kit contains all the necessary components and tubing to run one normothermic EVLP procedure on the XPS™*.

• Disposables for connecting the lungs to the perfusion circuit

• STEEN Solution™• XVIVO Organ Chamber™

• XVIVO Lung Cannula Set™• XVIVO PGM Disposable Sensors™

To facilitate your administrative work – simply order all items needed for an EVLP procedure directly with us. We have products in stock and arrange direct shipments from our facility. You can rely on our long experience of shipping products worldwide.

DIRECT, FAST AND PRECISE

WE SIMPLIFY YOUR ADMINISTRATIVE WORK

Training and workshops on-site

XVIVO Perfusion arranges workshops where transplant teams receive hands­on training on the EVLP concept. You may choose from a selection of workshops, individual or together with other international transplant teams. On­site training can also be customized to your local team and facility. Over the years we have arranged both local and regional workshops together with leading centers in Europe, Asia, Pacific, North and South America. Contact training@xvivoperfusion.com to learn more about our curriculum and activities in your region.

Installation and Technical Support

When a customer has decided to use the XPS™ in the clinic or for research, an XVIVO Perfusion certified Technical Advisor will together with your local coordinator arrange a two day installation and training session on site in the hospital. We will provide you with detailed manuals and check­lists. If you have any problems or need help, our dedicated staff will be happy to help you out.

Research and future therapies

XVIVO Perfusion supports research in the field of ex vivo organ perfusion, EVOP. We currently support teams worldwide in their strive to develop new applications and areas for EVOP. EVOP may in the future provide the opportunity to deliver personalized medicine for organs, i.e the opportunity to define specific diagnosis and deliver appropriate treatments to a metabolically active organ. Please join XVIVO Perfusion to fulfill the company’s mission to develop innovative products and solutions that will ultimately lead to the outcome that nobody should die waiting for an organ.

Metabolic Profile of Ex Vivo Lung Perfusate Yields Biomarkers for Lung Transplant Outcomes. Hsin MK, Zamel R, Cypel M, Wishart D, Han B, Keshavjee S, Liu M. Ann Surg. 2018 Jan;267(1):196­197.

Higher M30 and high mobility group box 1 protein levels in ex vivo lung perfusate are associated with primary graft dysfunction after human lung transplantation. Hashimoto K, Cypel M, Juvet S, Saito T, Zamel R, Machuca TN, Hsin M, Kim H, Waddell TK, Liu M, Keshavjee S. J Heart Lung Transplant. 2017 Jun 21. pii: S1053­2498(17)31870­3.

The role of interleukin-1ß as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion. Andreasson ASI, Borthwick LA, Gillespie C, Jiwa K, Scott J, Henderson P, Mayes J, Romano R, Roman M, Ali S, Fildes JE, Marczin N, Dark JH, Fisher AJ; DEVELOP­UK Investigators. J Heart Lung Transplant. 2017 Sep;36(9):985­995.

Real-Time Computed Tomography Highlights Pulmonary Parenchymal Evolution During Ex Vivo Lung Reconditioning. Sage E, De Wolf J, Puyo P, Bonnette P, Glorion M, Salley N, Roux A, Liu N, Chapelier A. Ann Thorac Surg. 2017 Jun;103(6):e535­e537.

Standard donor lung procurement with normothermic ex vivo lung perfusion: A prospective randomized clinical trial. Slama A, Schillab L, Barta M, Benedek A, Mitterbauer A, Hoetzenecker K, Taghavi S, Lang G, Matilla J, Ankersmit H, Hager H, Roth G, Klepetko W, Aigner C. J Heart Lung Transplant. 2017 Jul;36(7):744­753.

Ex Vivo Lung Perfusion Model to Study Pulmonary Tissue Extracellular Microvesicle Profiles. Vallabhajosyula P, Korutla L, Habertheuer A, Reddy S, Schaufler C, Lasky J, Diamond J, Cantu E 3rd. Ann Thorac Surg. 2017 Jun;103(6):1758­1766.

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion. Andreasson AS, Karamanou DM, Gillespie CS, Özalp F, Butt T, Hill P, Jiwa K, Walden HR, Green NJ, Borthwick LA, Clark SC, Pauli H, Gould KF, Corris PA, Ali S, Dark JH, Fisher AJ. Eur J Cardiothorac Surg. 2017 Mar 1;51(3):577­586.

Soluble Adhesion Molecules During Ex Vivo Lung Perfusion Are Associated With Posttransplant Primary Graft Dysfunction. Hashimoto K, Cypel M, Kim H, Machuca TN, Nakajima D, Chen M, Hsin MK, Zamel R, Azad S, Waddell TK, Liu M, Keshavjee S. Am J Transplant. 2016 Dec 15.

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK. Fisher A, Andreasson A, Chrysos A, Lally J, Mamasoula C, Exley C, Wilkinson J, Qian J, Watson G, Lewington O, Chadwick T, McColl E, Pearce M, Mann K, McMeekin N, Vale L, Tsui S, Yonan N, Simon A, Marczin N, Mascaro J, Dark J. Health Technol Assess. 2016 Nov;20(85):1­276

Outcomes after transplantation of lungs preserved for more than 12 h: a retrospective study. Yeung JC, Krueger T, Yasufuku K, de Perrot M, Pierre AF, Waddell TK, Singer LG, Keshavjee S, Cypel M. Lancet Respir Med. 2017 Feb;5(2):119­124.

Transplantation after ex vivo lung perfusion: A midterm follow-up. Wallinder A, Riise GC, Ricksten SE, Silverborn M, Dellgren G. J Heart Lung Transplant. 2016 Nov;35(11):1303­1310.

International Society for Heart and Lung Transplantation Donation After Circulatory Death Registry Report. Cypel M, Levvey B, Van Raemdonck D, Erasmus M, Dark J, Love R, Mason D, Glanville AR, Chambers D, Edwards LB, Stehlik J, Hertz M, Whitson BA, Yusen RD, Puri V, Hopkins P, Snell G, Keshavjee S; International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2015 Oct;34(10):1278­82.

Ventilatory Management During Normothermic Ex Vivo Lung Perfusion: Effects on Clinical Outcomes. Terragni PP, Fanelli V, Boffini M, Filippini C, Cappello P, Ricci D, Del Sorbo L, Faggiano C, Brazzi L, Frati G, Venuta F, Mascia L, Rinaldi M, Ranieri VM. Transplantation. 2016 May;100(5):1128­35.

The role of the endothelin-1 pathway as a biomarker for donor lung assessment in clinical ex vivo lung perfusion. Machuca TN, Cypel M, Zhao Y, Grasemann H, Tavasoli F, Yeung JC, Bonato R, Chen M, Zamel R, Chun YM, Guan Z, de Perrot M, Waddell TK, Liu M, Keshavjee S. J Heart Lung Transplant. 2015 Jun;34(6):849­57.

Lung transplantation with donation after circulatory determination of death donors and the impact of ex vivo lung perfusion. Machuca TN, Mercier O, Collaud S, Tikkanen J, Krueger T, Yeung JC, Chen M, Azad S, Singer L, Yasufuku K, de Perrot M, Pierre A, Waddell TK, Keshavjee S, Cypel M. Am J Transplant. 2015 Apr;15(4):993­1002.

Clinical Outcome of Patients Transplanted with Marginal Donor Lungs via Ex Vivo Lung Perfusion Compared to Standard Lung Transplantation. Fildes JE, Archer LD, Blaikley J, Ball AL, Stone JP, Sjöberg T, Steen S, Yonan N. Transplantation. 2015 May;99(5):1078­83.

Acute kidney injury after ex vivo lung perfusion (EVLP). Hauck J, Osho A, Castleberry A, Hartwig M, Reddy L, Phillips­Bute B, Swaminathan M, Mathew J, Stafford­Smith M. Transplant Proc. 2014 Dec;46(10):3598­602.

Functional outcomes and quality of life after normothermic ex vivo lung perfusion lung transplantation. Tikkanen JM, Cypel M, Machuca TN, Azad S, Binnie M, Chow CW, Chaparro C, Hutcheon M, Yasufuku K, de Perrot M, Pierre AF, Waddell TK, Keshavjee S, Singer LG. J Heart Lung Transplant. 2015 Apr;34(4):547­56.

Post EVLP Cold Preservation Period Is Associated With Clinical Outcomes, E. Arango Tomas. P. Sanchez, R.D. Davis, E. Cantu, M.J. Weyant, D. Lederer, P.C. Camp, B.P. Griffith, F. D’Ovidio J Heart Lung Transplant. 2015 Apr; 34, (4), S96–S97

Three center experience with clinical normothermic Ex Vivo lung perfusion. Cypel M, Aigner C, Sage E, et al. J Heart Lung Transplant. 2013;32:S16

Ex vivo lung perfusion increases the pool of lung grafts: analysis of its potential and real impact on a lungtransplant program. Boffini M, Ricci D, Barbero C, et al. Transplant Proc 2013;45:2624­6

The effect of ex vivo lung perfusion on microbial load in human donor lungs. Andreasson A, Karamanou DM, Perry JD, et al. J Heart Lung Transplant. 2014

Normothermic ex vivo. lung perfusion as an assessment of marginal donor lungs – the NOVEL lung trial. Sanchez PG, Davis RD, D’Ovidio F, et al. J Heart Lung Transplant 2013;32:S16­7

The NOVEL Lung Trial One-Year Outcomes. Sanchez PG, Davis RD, D’Ovidio F, et al. J Heart Lung Transplant 2014;33:S71­S2

Lung transplantation from initially rejected donors after ex vivo lung reconditioning: the French experience. Sage E, Mussot S, Trebbia G et al. Eur J Cardiothorac Surg. 2014 Nov;46(5):794­9

Functional outcomes and quality of life after normothermic ex vivo lung perfusion lung transplantation. Tikkanen JM, Cypel M, Machuca TN, et al. J Heart Lung Transplant. 2014 Oct 24. pii: S1053­2498(14)01416­8

Clinical ex vivo lung perfusion – pushing the limits. Aigner C, Slama A, Hötzenecker K et al. Am J Transplant. 2012;12:1839­1847

Early outcomes of bilateral sequential single lung transplantation after ex-vivo lung evaluation and reconditioning. Zych B, Popov AF, Stavri G et al. J Heart Lung Transplant. 2012;31:274­281

Experience with the first 50 ex vivo lung perfusions in clinical transplantation. Cypel M, Yeung JC, Machuca T, et al. J Thorac Cardiovasc Surg. 2012;144:1200­1206

Clinical transplantation of initially rejected donor lungs after reconditioning ex vivo. Ingemansson R et al. Ann Thorac Surg 2009;87:255­260

Ex vivo lung perfusion: initial Brazilian experience. Pego­Fernandes P M et al. J Bras Pneumol 2009;35:1107­1112

Update on donor assessment, resuscitation, and acceptance criteria, including novel techniques – non-heart-beating donor lung retrieval and ex vivo donor lung perfusion. Yeung J C et al. Thorac Surg Clin 2009;19:261­274

Technique for prolonged normothermic ex vivo lung perfusion. Cypel M et al. J Heart Lung Transplant 2008;27:1319­1325

Functional repair of human donor lungs by IL-10 gene therapy. Cypel M et al. Science Translation Medicine 2009;1:1­9

Normothermic ex vivo perfusion prevents lung injury compared to extended cold preservation for transplantation. Cypel M et al. Am J Transplant 2009;9:1­8

Transplantation of lungs from a non-heart-beating donor. Steen S, Sjöberg T, Pierre L, Liao Q, Eriksson L, Algotsson L. Lancet 2001 Mar 17;357:825­829

Ex vivo evaluation of nonacceptable donor lungs. Wierup P, Haraldsson A, Nilsson F, Pierre L, Scherstén H, Silverborn M, Sjöberg T, Westfeldt U, Steen S. Ann Thorac Surg. 2006;81:460­466

First human transplantation of a nonacceptable donor lung after reconditioning ex vivo. Steen S, Ingemansson R, Eriksson L, Pierre L, Algotsson L, Wierup P, Liao Q, Eyjolfsson A, Gustafsson R, Sjöberg T. Ann Thorac Surg. 2007;83:2191­2194

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XVIVO Perfusion AB, Box 53015, SE­400 14 Göteborg, Sweden xvivoperfusion.com

XPS™, STEEN Solution™, PERFADEX®, PERFADEX® Plus, XVIVO Organ Chamber™, XVIVO Lung Cannula Set™, Silicone Tubing Set™, XPS Disposable Lung Kit™, XVIVO Disposable Lung Circuit™, XVIVO Disposable Lung Kit™, XVIVO PGM Disposable Sensors™ are all trademarks of XVIVO Perfusion AB.

NOBODY SHOULD DIE WAITING FOR A NEW ORGANXVIVO Perfusion is a medical technology company focused on developing optimized solutions for organ, tissue and cell preservation and perfusion in connection with transplantation. The company is rooted in medical science.

XVIVO Perfusion collaborates with transplant teams to save lives. Our mission is to increase the survival rates of patients awaiting transplantation by supporting transplant teams in every way we can. We join forces with the transplant teams to give more patients a better life.

We provide our customers with solutions and systems that can improve the transplant process outcome and expand the organ donor pool.