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Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality. Normothermic machine perfusion of the liver improved early graft function, demonstrated by reduced peak serum aspartate transaminase levels and early allograft dysfunction rates, and improved organ utilization and preservation times, although no differences were seen in graft or patient survival.

Hypothermic oxygenated machine perfusion (HOPE) was recently tested in preclinical trials in kidney transplantation (KT). Here we investigate the effects of HOPE on extended-criteria-donation (ECD) kidney allografts (KA). Fifteen ECD-KA were submitted to 152 ± 92 min of end-ischemic HOPE and were compared to a matched group undergoing conventional-cold-storage (CCS) KT (n = 30). Primary (delayed graft function-DGF) and secondary (e.g. postoperative complications, perfusion parameters) endpoints were analyzed within 6-months follow-up. There was no difference in the development of DGF between the HOPE and CCS groups (53% vs. 33%, respectively; p = 0.197). Serum urea was lower following HOPE compared to CCS (p = 0.003), whereas the CCS group displayed lower serum creatinine and higher eGFR rates on postoperative days (POD) 7 and 14. The relative decrease of renal vascular resistance (RR) following HOPE showed a significant inverse association with serum creatinine on POD1 (r = − 0.682; p = 0.006) as well as with serum urea and eGFR. Besides, the relative RR decrease was more prominent in KA with primary function when compared to KA with DGF (p = 0.013). Here we provide clinical evidence on HOPE in ECD-KT after brain death donation. Relative RR may be a useful predictive marker for KA function. Further validation in randomized controlled trials is warranted. Trial registration: clinicaltrials.gov (NCT03378817, Date of first registration: 20/12/2017).

We review data showing that peripheral nerve injuries (PNIs) that involve the loss of a nerve segment are the most common type of traumatic injury to nervous systems. Segmental-loss PNIs have a poor prognosis compared to other injuries, especially when one or more mixed motor/sensory nerves are involved and are typically the major source of disability associated with extremities that have sustained other injuries. Relatively little progress has been made, since the treatment of segmental loss PNIs with cable autografts that are currently the gold standard for repair has slow and incomplete (often non-existent) functional recovery. Viable peripheral nerve allografts (PNAs) to repair segmental-loss PNIs have not been experimentally or clinically useful due to their immunological rejection, Wallerian degeneration (WD) of anucleate donor graft and distal host axons, and slow regeneration of host axons, leading to delayed re-innervation and producing atrophy or degeneration of distal target tissues. However, two significant advances have recently been made using viable PNAs to repair segmental-loss PNIs: (1) hydrogel release of Treg cells that reduce the immunological response and (2) PEG-fusion of donor PNAs that reduce the immune response, reduce and/or suppress much WD, immediately restore axonal conduction across the donor graft and re-innervate many target tissues, and restore much voluntary behavioral functions within weeks, sometimes to levels approaching that of uninjured nerves. We review the rather sparse cellular/biochemical data for rejection of conventional PNAs and their acceptance following Treg hydrogel and PEG-fusion of PNAs, as well as cellular and systemic data for their acceptance and remarkable behavioral recovery in the absence of tissue matching or immune suppression. We also review typical and atypical characteristics of PNAs compared with other types of tissue or organ allografts, problems and potential solutions for PNA use and storage, clinical implications and commercial availability of PNAs, and future possibilities for PNAs to repair segmental-loss PNIs.

In the context of COVID-19 pandemic, we aimed to analyze the epidemiology, clinical characteristics, risk factors for mortality and impact of COVID-19 on outcomes of solid organ transplant (SOT) recipients compared to a cohort of non transplant patients, evaluating if transplantation could be considered a risk factor for mortality. From March to May 2020, 261 hospitalized patients with COVID-19 pneumonia were evaluated, including 41 SOT recipients. Of these, thirty-two were kidney recipients, 4 liver, 3 heart and 2 combined kidney-liver transplants. Median time from transplantation to COVID-19 diagnosis was 6 years. Thirteen SOT recipients (32%) required Intensive Care Unit (ICU) admission and 5 patients died (12%). Using a propensity score match analysis, we found no significant differences between SOT recipients and non-transplant patients. Older age (OR 1.142; 95% [CI 1.08–1.197]) higher levels of C-reactive protein (OR 3.068 ; 95% [CI 1.22–7.71]) and levels of serum creatinine on admission (OR 3.048 95% [CI 1.22–7.57]) were associated with higher mortality. The clinical outcomes of SARS-CoV-2 infection in our cohort of SOT recipients appear to be similar to that observed in the non-transplant population. Older age, higher levels of C-reactive protein and serum creatinine were associated with higher mortality, whereas SOT was not associated with worse outcomes.

Background Recent studies suggest that alterations in lung microbiome are associated with occurrence of chronic lung diseases and transplant rejection. To investigate the host-microbiome interactions, we characterized the airway microbiome and metabolome of the allograft (transplanted lung) and native lung of single lung transplant recipients. Methods BAL was collected from the allograft and native lungs of SLTs and healthy controls. 16S rRNA microbiome analysis was performed on BAL bacterial pellets and supernatant used for metabolome, cytokines and acetylated proline-glycine-proline (Ac-PGP) measurement by liquid chromatography-high-resolution mass spectrometry. Results In our cohort, the allograft airway microbiome was distinct with a significantly higher bacterial burden and relative abundance of genera Acinetobacter & Pseudomonas . Likewise, the expression of the pro-inflammatory cytokine VEGF and the neutrophil chemoattractant matrikine Ac-PGP in the allograft was significantly higher. Airway metabolome distinguished the native lung from the allografts and an increased concentration of sphingosine-like metabolites that negatively correlated with abundance of bacteria from phyla Proteobacteria . Conclusions Allograft lungs have a distinct microbiome signature, a higher bacterial biomass and an increased Ac-PGP compared to the native lungs in SLTs compared to the native lungs in SLTs. Airway metabolome distinguishes the allografts from native lungs and is associated with distinct microbial communities, suggesting a functional relationship between the local microbiome and metabolome.

We analyzed cortical renal blood flow (cRBF) by ASL-MRI in ten donors (4 females, mean age 46 ± 6) and dedicated pediatric recipients (4 females, mean age 14 ± 4) before transplantation and at 3-, 6-, and 12-months post-transplant to identify allograft functional adaptation. Baseline values were compared to post-transplant values and correlated with estimated glomerular filtration rate (eGFR). Additionally, renal plasma flow (RPF) and estimated filtration fraction (eFF) were calculated. Both cRBF and eGFR demonstrated a highly significant increase at 3 months compared to baseline (mean cRBF 251.71 ± 78.27 vs. 486.61 ± 156.08 ml/kidney/min, p  = 0.0001; mean eGFR 46.62 ± 16.36 vs. 69.81 ± 24.83 ml/min/1.73 m 2 ; p  = 0.02) and remained consistent until the end of the observed period. Patients with impaired function and lower eGFR at 3 months exhibited a smaller increase in cRBF compared to the rest of the group ( p  = 0.01). eFF did not change significantly throughout the observed period ( p  = 0.07, p  = 0.07, and p  = 0.68, respectively), suggesting absence of hyperfiltration. cRBF may serve as a significant renal biomarker for longitudinal follow-up of renal allografts, enabling tracking of perfusion adaptation and identification of critical timepoints for clinical intervention.

Massive bone allograft decellularized by perfusion is a solution for large bone defect reconstructions. Perfusion-based decellularization offers a solution by removing cellular components while preserving the non-immunogenic matrix. This study evaluates the in vivo integration and mechanical properties of perfusion-decellularized bone grafts compared to “fresh-frozen” grafts, both before implantation and after explantation. Standardized porcine femoral grafts were categorized into non-irradiated, irradiated, and explanted groups, with half undergoing perfusion decellularization. Biomechanical tests, including screw pull-out test, compression, and 3-point bending test, were performed. Results indicate that while decellularization increases graft brittleness, Vickers indentation and compression tests showed no significant differences between groups. In our study, decellularization reduced the mechanical strength of allografts both before and after implantation. However, since the risk of rupture occurred only under mechanical loads exceeding the physiological range, perfusion-decellularized bone grafts remain a valid strategy for bone repair.

Hand and upper extremity transplantation (HUET) has emerged as the most frequently performed reconstructive procedure in the burgeoning field of vascularized composite allotransplantation (VCA). VCA refers to a form of transplant with multiple tissue types that represents a viable treatment option for devastating injuries where conventional reconstruction would be unable to restore form and function. As hand transplantation becomes increasingly more common, discussions on advantages and disadvantages of the procedure seem to intensify. Despite encouraging functional outcomes, current immunosuppressive regimens with their deleterious side-effect profile remain a major concern for a life-changing but not life-saving type of transplant. In addition, a growing number of recipients with progressively longer follow-up prompt the need to investigate potential long-term sequelae, such as chronic rejection. This review will discuss the current state of HUET, summarizing outcome data on graft survival, motor and sensory function, as well as immunosuppressive treatment. The implications of these findings for VCA in terms of achievements and challenges ahead will then be discussed.

Implantation of allograft tissues has massively grown over the last years, especially in the fields related to sports medicine. Beside the fact that often no autograft option exists, autograft related disadvantages as donor-site morbidity and prolonged operative time are drastically reduced with allograft tissues. Despite the well documented clinical success for bone allograft procedures, advances in tissue engineering raised the interest in meniscus, osteochondral and ligament/tendon allografts. Notably, their overall success rates are constantly higher than 80%, making them a valuable treatment option in orthopaedics, especially in knee surgery. Complications reported for allografting procedures are a small risk of disease transmission, immunologic rejection, and decreased biologic incorporation together with nonunion at the graft-host juncture and, rarely, massive allograft resorption. Although allografting is a successful procedure, improved techniques and biological knowledge to limit these pitfalls and maximize graft incorporation are needed. A basic understanding of the biologic processes that affect the donor-host interactions and eventual incorporation and remodelling of various allograft tissues is a fundamental prerequisite for their successful clinical use. Further, the importance of the interaction of immunologic factors with the biologic processes involved in allograft incorporation has yet to be fully dissected. Finally, new tissue engineering techniques and use of adjunctive growth factors, cell based and focused gene therapies may improve the quality and uniformity of clinical outcomes. The aim of this review is to shed light on the biology of meniscus, osteochondral and ligament/tendon allograft incorporation and how collection and storage techniques may affect graft stability and embodiment. Level of evidence V.

Because chronic lung allograft dysfunction (CLAD) develops predominantly on one side after bilateral living-donor lobar lung transplantation (LDLLT), lung perfusion scintigraphy (Q-scinti) was expected to show a perfusion shift to the contralateral unaffected lung with the development of CLAD. Our study examined the potential usefulness of Q-scinti in the diagnosis of CLAD after bilateral LDLLT. We conducted a single-center retrospective cohort study of 58 recipients of bilateral LDLLT. The unilateral shift values on Q-scinti were calculated and compared between the CLAD group (N = 27) and the non-CLAD group (N = 31) from 5 years before to 5 years after the diagnosis of CLAD. The unilateral shift values in Q-scinti were significantly higher in the CLAD group than in the non-CLAD group from 5 years before the diagnosis of CLAD to 5 years after the diagnosis ( P  < 0.05). The unilateral shift values in Q-scinti were significantly correlated with the percent baseline values of the forced expiratory volume in 1 s ( P  = 0.0037), the total lung capacity ( P  = 0.0028), and the forced vital capacity ( P  = 0.00024) at the diagnosis of CLAD. In patients developing unilateral CLAD after bilateral LDLLT, Q-scinti showed a unilateral perfusion shift to the contralateral unaffected lung. Thus, Q-scinti appears to have the potential to predict unilateral CLAD after bilateral LDLLT.