Background. Normothermic machine perfusion (NMP) bears the potential for significant prolongation of liver preservation before transplantation. Although safety and feasibility have been recently published, no data are available describing the significant challenges of establishing NMP programs outside clinical studies. We herein present our experience and propose a multidisciplinary approach for liver NMP in the clinical routine. Methods. In February 2018, liver NMP was introduced for routine use in marginal organs, logistic challenges, and complex recipients at our institution. In a multidisciplinary effort among transplant coordinators, perfusionists, transplant surgeons, anesthesia, nurses, blood bank as well as laboratory staff, a clinical routine was established and 34 NMP cases were performed without critical incidents or organ loss. Results. Nine livers were discarded due to poor organ quality and function observed during NMP. Twenty-five livers were successfully transplanted after preservation of up to 38 h. The extended criteria donors rate was 100% and 92% in discarded and transplanted livers, respectively. Nighttime procedures and parallel transplantations were eventually omitted. Graft and patient survival was 88% at 20 mo. No cholangiopathy was observed despite the use of extended criteria donor organs in 92% of cases. Conclusions. NMP in a multidisciplinary approach enables a safe prolongation of liver preservation and overnight organ care. A first field test of NMP indicates safety and benefit of this approach.

We here report on the surgical procedure, postoperative course and functional results at 3 years following the first bilateral forearm transplantation. A 41-year-old male underwent bilateral forearm transplantation on February 17, 2003. After ATG induction therapy, tacrolimus, prednisone and MMF were given for maintenance immunosuppression. At 16 months, MMF was switched to everolimus. Hand function, histology, immunohistochemistry, radiomorphology, motor and nerve conduction and somatosensory-evoked potentials were investigated at frequent intervals. A total of six rejection episodes required treatment with either steroids, basiliximab, ATG, alemtuzumab or tacrolimus dose augmentation. At 3 years, the patient is free of clinical signs of rejection despite a persisting minimal perivascular lymphocytic dermal infiltrate. No signs of myointimal proliferation in graft vessels were seen. Motor function continuously improved, resulting in satisfactory hand function. Intrinsic hand muscle function was first observed at 16 months and continues to improve. Although discrimination of hot and cold recovered, overall sensitivity remains poor. The patient is satisfied with the outcome. Bilateral forearm transplantation represents a novel therapeutic option after loss of forearms. † These authors contributed equally to this work.

Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E-and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 ± 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E-and P-selectin in the skin holds potential to significantly prolong limb allograft survival.

Summary The aim of this work is to compare disabilities of the upper limb before and after hand allograft transplantation (HAT), and to describe the side effects of immunosuppressive (IS) agents given to recipients of hand allografts. Clinical cases of HAT published between 1999 and 2011 in English, French, or German were reviewed systematically, with emphasis on comparing disabilities of the arm, shoulder and hand (DASH) scores before and after transplantation. Duration of ischemia, extent of amputation, and time since amputation were evaluated for their effect on intrinsic musculature function. Infectious, metabolic, and oncological complications because of IS therapy were recorded. Twenty‐eight patients were reported in 56 clinical manuscripts. Among these patients, disabilities of the upper limb dropped by a mean of 27.6 (±19.04) points on the DASH score after HAT (P = 0.005). Lower DASH scores (P = 0.036) were recorded after secondary surgery on hand allografts. The presence of intrinsic muscle function was observed in 57% of the recipients. Duration of ischemia, extent of transplantation, and time since amputation were not associated statistically with the return of intrinsic musculature function. Three grafts were lost to follow‐up because of noncompliance with immunosuppression, rejection, and arterial thrombosis, respectively. Fifty‐two complications caused by IS agents were reported, and they were successfully managed medically or surgically. HAT recipients showed notable functional gains, but most complications resulted from the IS protocols.

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'Transplant psychology' -General psychological considerationsThe human hand represents a powerful physical instrument, with a variety of psychosocial functions and roles. From a psychosocial perspective, the human hand assists in interpersonal communication through touch and gestures. Humans communicate, greet each other, demonstrate intimacy and love, form and break bonds, protect and attack [1]. Reconstructive hand transplantation (RHT) represents an enormous medical advance involving parts of human anatomy that play such an important role in making us human [2].Reconstructive hand transplantation has been one of the most striking medical success stories although it differs from other forms of transplantation in numerous

SummaryClinical relevance of antibody-mediated rejection (ABMR) in vascularized composite allotransplantation (VCA) has not been defined. We herein describe a novel type of donor-specific antibody (DSA) and B-cell-associated rejection in hand transplantation. In 2003, a bilateral forearm transplantation was performed on a 42-year-old male patient. In 2012, the patient presented with edematous hands and forearms without skin lesions. Punch skin biopsies revealed rejection grade Banff II. Immunohistochemical analysis identified large aggregates of CD20 + lymphocytes with an architecture resembling lymph nodes. De novo DSA was found at a high level. Steroid treatment was ineffective, but administration of rituximab resulted in complete remission of clinical symptoms, evaporation of B-cell aggregates, and disappearance of DSA. We herein report the first case of what we suggest is an ABMR in VCA occurring at 9 years after forearm transplantation. Rituximab therapy successfully reversed the event.

Mitochondria sense changes resulting from the ischemia and subsequent reperfusion of an organ and mitochondrial reactive oxygen species (ROS) production initiates a series of events, which over time result in the development of full-fledged ischemia-reperfusion injury (IRI), severely affecting graft function and survival after transplantation. ROS activate the innate immune system, regulate cell death, impair mitochondrial and cellular performance and hence organ function. Arresting the development of IRI before the onset of ROS production is currently not feasible and clinicians are faced with limiting the consequences. Ex vivo machine perfusion has opened the possibility to ameliorate or antagonize the development of IRI and may be particularly beneficial for extended criteria donor organs. The molecular events occurring during machine perfusion remain incompletely understood. Accumulation of succinate and depletion of adenosine triphosphate (ATP) have been considered key mechanisms in the initiation; however, a plethora of molecular events contribute to the final tissue damage. Here we discuss how understanding mitochondrial dysfunction linked to IRI may help to develop novel strategies for the prevention of ROS-initiated damage in the evolving era of machine perfusion.