Normothermic ex vivo perfusion of the limb allograft depletes donor leukocytes prior to transplantation

Amin, Kavit; Stone, J.J.; Jc, Kerr; Jk, Wong; Fildes, JE

doi:10.1016/j.bjps.2021.03.071

Cited by 10 publications

(11 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A comprehensive review of current hand transplantation research goes well beyond the scope of this article, but it would be remiss not to acknowledge the broad spectrum of work being undertaken to advance our understanding of the fundamental immunological processes at play, and the factors influencing risk and clinical outcomes. The range of relevant basic science and translational inquiry is extensive, including topical and targeted immunosuppression delivery (Feturi et al, 2022), ex-vivo perfusion (Amin et al, 2021), graft modification to reduce immunogenicity (Lei et al, 2021) and the continued effort to characterize the mechanisms of immune recognition and response, with the ultimate aim of unlocking the door to transplantation without the need for lifelong immunosuppression (transplant tolerance) (Leonard et al, These efforts are of critical importance, but since both introduction of major new advances, and assessment of outcomes within current clinical practice, ultimately rely upon statistically valid comparisons there is also a pressing need for robust reporting. So, while the number of cases undertaken by any one unit remains relatively small, achieving a statistically robust dataset will necessitate greater collaboration between units.…”

Section: Addressing the Unknownmentioning

confidence: 99%

Section: Communicating and Understanding Risk And Understanding ‘Unde...mentioning

confidence: 99%

See 1 more Smart Citation

Hand transplantation: can we balance the risks and benefits?

Kay

Leonard

2023

J Hand Surg Eur Vol

View full text Add to dashboard Cite

Asking ‘can we balance the risks and benefits?’ implies that a quantification of both risk and benefit in hand transplantation (here the terms hand transplant and hand transplantation refer to allotransplantation of the human hand or hand and part or all of the upper limb or limbs) is possible. Despite all we have learned in recent years about hand transplantation, much remains unknown. Even if reliable methods for quantification of risk and benefit were available, fundamental issues relating to effective communication across the gulf of lived experience between the (presumably) handed surgeon and the handless patient remain. Inherent complexities mean some consider hand transplantation an unsolved problem, but we believe the medical and technical considerations fall within the ambit of a competent multidisciplinary team, and that psychosocial and ethical challenges are open to management through robust frameworks for assessment and decision making, underpinned by an extended period of assessment and dialogue, with candid acknowledgement where uncertainty remains. This respects the patient’s autonomy while addressing the need for a prolonged period of informing consent. Level of evidence: V

show abstract

Section: Addressing the Unknownmentioning

confidence: 99%

Section: Communicating and Understanding Risk And Understanding ‘Unde...mentioning

confidence: 99%

Hand transplantation: can we balance the risks and benefits?

Kay

Leonard

2023

J Hand Surg Eur Vol

View full text Add to dashboard Cite

show abstract

“…Machine perfusion (MP) studies by our lab demonstrate that continuous flow throughout the vasculature of the allograft is vasoprotective (reduced intravascular resistance) with removal of leukocytes and cytokines from the microcirculation (44). Protocols should contemplate the handling of the graft and its condition prior, during and after perfusion.…”

Section: Machine Perfusionmentioning

confidence: 99%

Bionic Prostheses: The Emerging Alternative to Vascularised Composite Allotransplantation of the Limb

Amin

Fildes

2022

Front. Surg.

View full text Add to dashboard Cite

Twenty years have surpassed since the first vascularised composite allotransplantation (VCA) of the upper limb. This is an opportunity to reflect on the position of VCA as the gold standard in limb reconstruction. The paucity of recipients, tentative clinical outcomes, and insufficient scientific progress question whether VCA will remain a viable treatment option for the growing numbers of amputees. Bionic technology is advancing at a rapid pace. The prospect of widely available, affordable, safely applied prostheses with long-standing functional benefit is appealing. Progress in the field stems from the contributions made by engineering, electronic, computing and material science research groups. This review will address the ongoing reservations surrounding VCA whilst acknowledging the future impact of bionic technology as a realistic alternative for limb reconstruction.

show abstract

“…They concluded that this depletion could mitigate acute rejection and graft dysfunction following replantation. 12 Although extended preservation of the extremities can be achieved with EVNLP, 13 the machine perfusion systems lack metabolic, endocrine, neurologic, and excretory homeostatic functions. Gradual loss of tissue viability occurs, resulting in increased vascular resistance and compartment pressure that necessitates perfusion termination.…”

Section: Introductionmentioning

confidence: 99%

“…Amin et al implemented EVNLP for both preservation and donor immunodepleting, finding that the limb allograft released leukocytes and cytokines throughout perfusion. They concluded that this depletion could mitigate acute rejection and graft dysfunction following replantation 12 …”

Section: Introductionmentioning

confidence: 99%

Weight gain is an early indicator of injury in ex vivo normothermic limb perfusion (EVNLP)

et al. 2022

View full text Add to dashboard Cite

Purpose There are no established criteria for discontinuing ex vivo normothermic limb perfusion (EVNLP) before irreversible damage occurs. This study evaluates weight gain as an indicator of injury during EVNLP. Methods Sixteen Yorkshire pig forelimbs were procured and preserved using EVNLP with a hemoglobin‐based oxygen carrier (HBOC‐201) or static cold storage. EVNLP continued until termination criteria were met: arterial pressure ≥ 115 mm Hg, compartment pressure > 30 mm Hg, or 20% reduction of oxygen saturation. Limb weight, contractility, hemodynamics, perfusate electrolytes, metabolites and gases were recorded. Muscles were biopsied 6‐h, and muscle injury scores (MIS) calculated. Forearm compartment pressures and indocyanine green (ICG) angiography were recorded at endpoint. Outcomes were compared at 2%, 5%, 10%, and 20% limb weight gain. Results EVNLP lasted 20 ± 3 h. Weight gain was observed after 13 ± 5 h (2%), 15 ± 6 h (5%), 16 ± 6 h (10%), and 19 ± 4 h (20%). Weight correlated positively with MIS (ρ = 0.92, p < 0.0001), potassium (ρ = −1.00, p < 0.0001), pressure (ρ = 0.78, p < 0.0001), and negatively with contractility (ρ = −0.96, p = 0.011). At 5% weight gain, MIS (p < 0.0001), potassium (p = 0.03), and lactate (p < 0.0001) were significantly higher than baseline. Median muscle contractility was 5 [3–5] at 2% weight gain, 4 [1–5] at 5%, 3 [0–4] and 2 [0–2] at 10% and 20%, respectively. At 20% weight gain, contractility was significantly lower than baseline (p = 0.003). Percent weight gain correlated negatively with endpoint ICG hoof fluorescence (r = −0.712, p = 0.047). Conclusions Weight gain correlated with microscopic muscle injury and was the earliest evidence of limb dysfunction. Weight gain may serve as a criterion for discontinuation of EVNLP.

show abstract

Normothermic ex vivo perfusion of the limb allograft depletes donor leukocytes prior to transplantation

Cited by 10 publications

References 26 publications

Hand transplantation: can we balance the risks and benefits?

Hand transplantation: can we balance the risks and benefits?

Bionic Prostheses: The Emerging Alternative to Vascularised Composite Allotransplantation of the Limb

Weight gain is an early indicator of injury in ex vivo normothermic limb perfusion (EVNLP)

Contact Info

Product

Resources

About