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Tailoring Treatment for Transplant and Prosthetics Patients

W. P. Andrew Lee, Jaimie Shores, and Gerald Brandacher

Quality of life is crucial when considering options for a patient with severe hand or upper extremity in­jury. With a rapidly expanding range of approaches, Johns Hopkins specialists are increasingly able to tailor treatment to a patient’s preference and medical situation, restoring as much as possible of the patient’s life.

For patients with appropriate medical, psychological, and social in­dicators, a hand or upper limb transplant is becoming an ever more viable option. The team of W. P. Andrew Lee, Jaimie Shores, Gerald Brandacher, and their colleagues is setting a standard in this new field. Having transplanted 10 limbs across six patients (including the only two above-elbow transplants in the United States), the team members have some of the most extensive experience in the world. And, based on that experience, they have developed advanced methods that will likely make transplantation available to even more patients.

While transplantation is a complex procedure (which involves add­ing new skeletal and soft tissues, re-routing nerves, and reconnecting blood vessels), its greatest limiting factor is the patient’s tolerance of the immunosuppression treatment that is required. Because the sur­gery isn’t lifesaving, subjecting patients to the rigors of standard triple-drug immunosuppression for a lifetime has the potential to do more harm than good.

So Brandacher helped design—and is constantly refining—a groundbreaking protocol of minimal immunosuppression. Such a shift in the risk-benefit ratio brings limb transplanta­tion into reach for more patients and also offers possible benefits for solid organ transplant recipient.

“Because side effects and drug toxicities are minimized, this protocol could open up the field of extremity transplantation to become more mainstream,” says Brandacher.

The gentler protocol involves an antibody to deplete immune cells at the time of transplan­tation, followed by a single immunosuppressive agent at low levels immediately after surgery. Two weeks later, bone marrow cells from the donor are infused to modulate—rather than indiscriminately suppress—the recipient immune system, helping the recipient tolerate the graft with minimal medication.

“There are other centers in the world that perform hand and face transplants, but our pro­gram is unique in using an immuno-modulatory protocol that minimizes the side effects of medications for the transplant recipients. We believe it is a critical aspect to make these types of transplants widespread,” Lee says.

Another limiting factor in upper extremity restoration is nerve regeneration. Surgeons can transplant a limb, but if the nerves don’t grow back into the muscles robustly, the limb won’t function adequately. A concomitant effect of the main immunotherapy drug in Brandacher’s protocol is that it helps stimulate nerve regeneration.

“If the nerve regeneration problem was eliminated, it would expand the pool of candidates for transplantation for upper extremity and may open the door for lower extremity as well,” Shores says. “The advances we make for hand transplants not only benefit our program, but may benefit all types of transplants.”

Targeted Muscle Reinnervation: A Feat of Engineering

For those patients not suitable for a transplant but dissatisfied with a traditional prosthesis, targeted muscle reinnervation (TMR) provides a viable option. In TMR, surgeons re-route the peripheral nervous system in the residual stump to better integrate the prosthesis with the patient’s neuromuscular system.

Patients undergo intensive therapy in order to learn how to use the prosthetic. In a virtual reality lab, the patient’s stump is hooked to a computer. As the patient watches a virtual arm on the screen, he or she pretends to do activities like making a fist or extending his or her fingers.

“Conventional prosthetics have a certain number of degrees of freedom, and you hit a switch to move them. These new ones, all you have to do is think about it,” says Richard Redett.

If the process sounds like a feat of engineering, it is; Redett and Shores, along with trauma surgeon Albert Chi (director of the TMR Program), work very closely with colleagues at Johns Hopkins’ Applied Physics Laboratory. The next step in this collaboration is to integrate the sensory component as well. With targeted sensory reinnervation, surgeons will be able to put sensors on a prosthetic’s fingertips that send signals back to muscle, nerves, or skin, making patients think they have feeling in the tip of the prosthesis.


An Umbrella of Care for Upper Extremity Restoration

Harnessing the expertise of a wide range of specialists, the Johns Hopkins Center for Upper Extremity Restoration (CUER) offers the kind of comprehensive care that makes it the most complete upper extremity program of its kind.

An umbrella for any devastating upper extremity problem, the center surrounds a patient with hand surgeons, reconstructive microvascular surgeons, transplant surgeons, trauma surgeons, and physical medicine and rehabilitation specialists to evaluate the condition from every angle and make a treatment recommendation tailored for that particular patient.

Treatments may range from reconstructive surgery to advanced prosthetic options and TMR to hand or upper limb transplantation.

The ability to so fully evaluate a patient, combined with the availability of expertise to implement the chosen treatment, aims to transform the care for upper extremity amputees.

“This will become the paradigm for evaluating patients with upper extremity and hand loss,” says Jaimie Shores, clinical director of hand and upper extremity transplantation.

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