Scarcity Of Grafts Research Articles

Hepatic Artery Thrombectomy after Orthotopic Liver Transplantation: A Stent Retriever and/or Aspiration-Guided Catheter Approach

Retransplantation has been the primary treatment for hepatic artery thrombosis (HAT) in patients with orthotopic liver transplant (OLT); however, because of scarcity of grafts, endovascular revascularization via mechanical thrombectomy offers an alternative to retransplantation should it provide similar long-term benefits. Data regarding a series of 8 patients with hepatic artery thrombectomies across 10 procedures (1 early HAT and 9 late HAT) utilizing stent retriever and/or suction catheter were collected. All had technically successful restoration of flow with stent placement of the anastomotic stenosis in 8 cases. Two patients required reintervention for HAT at 18 and 701 days after primary intervention, with the first dying from liver failure but with a patent hepatic artery on explant. One case had a procedure-related adverse event, hepatic artery dissection, Society of Interventional Radiology (SIR) adverse event classification of 2. Technical success was achieved in all procedures, demonstrating promise in effectively treating HAT in patients with OLT.

A Review of Advanced Biomaterials and Cells for the Production of Bone Organoid

Rapid advancements in traditional bone tissue engineering have led to innovation in bone repair models and the resolution of insurmountable clinical issues like graft scarcity. The pathophysiological process of treating bone disease, however, is a multidimensional and multimodal regenerative regulatory mechanism that includes numerous immune, inflammatory, or metabolic responses related to the graft or the organism itself. Based on a 3D in vitro cell culture system that is remarkably identical to the body's bone tissue, the bone organoid is a biomimicking bone organ environment. It can accurately mimic the actual repair and regeneration condition in vivo because it shares the same physiological function, structure, morphology, and metabolic process as endogenous bone tissue. As a disruptive regenerative medicine technology, it has wide application prospects in the fields of organ development, gene editing, disease modeling, and precision therapy. Herein, the development process and physiological basis of different cell‐based bone organoids are reviewed, the current status of the application of different materials, cells, and construction methods for building bone organoids is described, and the prospects and challenges for the development of bone organoids in future medical fields is discussed.

Simulated model of RAPID concept: highlighting innate inflammation and liver regeneration.

BackgroundThe resection and partial liver segment II/III transplantation with delayed total hepatectomy (RAPID) concept is a novel transplantation technique for removal of non‐resectable liver tumours. The aim of this study was to establish a simulated RAPID model to explore the mechanism involved in the liver regeneration.MethodsA RAPID model was created in rats involving cold ischaemia and reperfusion of the selected future liver remnant (FLR), portal vein ligation, followed by resection of the deportalized lobes in a second step. Histology, liver regeneration and inflammatory markers in RAPID‐treated rats were compared with those in controls that underwent 70 per cent hepatectomy with the same FLR size. The effects of interleukin (IL) 6 and macrophage polarization on hepatocyte viability were evaluated in an in vitro co‐culture system of macrophages and BRL hepatocytes.ResultsThe survival rate in RAPID and control hepatectomy groups was 100 per cent. The regeneration rate was higher in the RAPID‐treated rats, with higher levels of IL‐6 and M1 macrophage polarization (P < 0·050). BRL hepatocytes co‐cultured with M1 macrophages showed a higher proliferation rate through activation of the IL‐6/signal transducer and activator of transcription 3/extracellular signal‐regulated kinase pathway. This enhancement of proliferation was inhibited by tocilizumab or gadolinium trichloride (P < 0·050).ConclusionThe surgical model provides a simulation of RAPID that can be used to study the liver regeneration profile. Surgical RelevanceThe mechanisms sustaining liver regeneration are a relevant field of research to reduce the ‘small for size’ liver syndrome when the future liver remnant is not adequate. Several surgical strategies have been introduced both for liver resection and transplant surgery, mostly related to this issue and to the scarcity of grafts, among these the RAPID concept involving the use of an auxiliary segment II/III donor liver that expands to a sufficient size until a safe second‐stage hepatectomy can be performed. Understanding the mechanisms and pitfalls of the liver regeneration profile may help in tailoring surgical strategies and in selecting patients. In this experimental model the authors investigated liver histology, regeneration and inflammatory markers in RAPID‐treated rats.

Use of Extended-Donor Criteria Hearts in Amyloidosis Patients Demonstrates Similar Morbidity and Mortality Compared to Non-Amyloid Recipients

Advances in amyloidosis management have improved patient longevity. Coupling potential increased transplantation for amyloid patients with graft scarcity, we intend to assess the use of extended-donor criteria (EDC) hearts for amyloidosis. Retrospective review of heart transplants from the national Organ Procurement and Transplantation Network database from 1/'08 to 6/'19. Recipients were stratified first by amyloidosis diagnosis and subsequently by use of EDC grafts. Propensity-score matching (PSM) between amyloid and non-amyloid groups addressed confounding variables. Baseline and PSM baseline characteristics and transplant outcomes were compared across groups. 30,414 patients met inclusion criteria. 444 (1.5%) carried a primary diagnosis of amyloidosis. Amyloid patients were older (average age 63.5 vs 53 p<0.001), with advanced comorbidities and were more likely to be transplanted from an ICU setting (44.8 vs 33.2% p<0.001) than non-amyloid counterparts. Neither amyloid or non-amyloid populations receiving EDC grafts demonstrated significantly worse patient or graft survival compared to recipients with allografts from non-EDC donors. The relative attributable risk of EDC grafts was not significantly different between amyloid and non-amyloid populations relating to patient and graft survival. PSM reaffirmed these results. Amyloid patients did note a higher post-operative rate of renal failure requiring dialysis which became more pronounced in EDC grafts (p for heterogeneity=0.004). Improvements in management of cardiac amyloidosis strengthen the argument for transplantation, although greater transplant rates would further imbalance the donor-recipient supply and demand. Utilization of EDC grafts in amyloid patients appears a safe and feasible option, although further surveillance is warranted to ensure optimal donor-recipient matching.

An insight into cell-laden 3D-printed constructs for bone tissue engineering.

Escalating bone graft scarcity and donor site morbidity worldwide are alarming reminders that highlight the need for alternatives to gold standard tissue rejuvenation methods. Over the last few decades, many efforts have been made in bone tissue engineering (BTE) to fabricate artificial bone transplants. Conventional BTE techniques do not render pertinent spatial organization of cells, and they fail in mimicking the extracellular matrix of native bone tissue. This setback can be overcome by using the emerging technology of three-dimensional bioprinting (3DBP). 3DBP is a state-of-the-art technology that provides accurate hierarchal biomaterial structures that accommodate live-cell patterning to mimic their native counterparts. Herein, we provide an overview on the recent progress of cell-laden 3DBP technologies and also discuss the various biomaterials utilized (natural polymers such as chitosan, collagen, gelatin, hyaluronic acid, and silk fibroin and synthetic polymers such as PCL, PVP, and ceramics) to engineer scaffolds with requisite structural, mechanical, and biological complexity. We also highlight some of the persisting challenges and the solutions to surmount them, paving the way for progress in the field. Finally, we discuss how the combination of novel modalities with 3DBP can pave the way for new frontiers, like four-dimensional bioprinting (4DBP), to bring customized, stimuli-responsive, and highly effective regenerative scaffolds to bone tissue engineering.

Current Status and Future Challenges of Liver Transplantation Programs in Chile.

Liver transplantation (LT) was performed for the first time in Chile in 1969, but only since the 1990s has it been systematically performed. Our health system is strongly centralized, which is a severe limitation for the patients who need to be evaluated and subsequently listed. Although proper human and technological resources are available and our results are comparable to international outcomes (overall patient survival at 1, 5, and 10 years of 82%, 70%, and 64%, respectively), we are limited because of a severe scarcity of grafts, which translates into an availability of approximately 7 organs per million persons and a wait-list dropout rate of 40% every year. Thus, our main challenge for the next few years is to improve access to LT among the populations from the extreme regions of the country and overall to improve the availability of grafts by increasing the awareness of physicians in intensive care units and emergency departments, to develop living donor LT programs, to educate the population in order to decrease family refusal, and to reinforce the system of potential donor detection. Although hard work is mandatory for these improvements, none of these tasks seem to be unreachable in the midterm.

Excellent Outcomes of Deceased Donor Liver Transplantation Using Grafts From Older Donors: A U.S. Single-Center Experience

Introduction: One of the major challenges in deceased donor liver transplantation (DDLT) is the scarcity of donor allografts, which results in high wait-list mortality. Transplant centers tackle the donor graft scarcity by utilizing expanded criteria donors including older donors. UNOS reported that the percentage of donor age > 50 years rose from 24% in 1989 to 33% in 2013. The literature on the impact of older donor age on liver graft function, survival and complications have described contradictory results. In this study, we aim to evaluate patient and graft survival outcomes of DDLT recipients in 2 groups: donor age ≥65 years and donor age < 65 years. Methods: Setting: Single center Retrospective cohort study at a large volume US liver transplant center Inclusion criteria: All primary deceased liver transplants (DDLT) in our institution between October 2012 to October 2016 Exclusion criteria: age <18, split and reduced-size livers and multi-organ transplants were excluded from the study Outcomes: Comparison of 1-year /overall patient and graft survival in 2 groups: donor age ≥65 years and donor age < 65 years. Results: In total, 646 patients met inclusion criteria. Among patients who underwent DDLT, 70 (11%) received DDLT from older (>65 years) donors. There was no difference in age, sex, ethnicity, hepatocellular carcinoma, warm/cold ischemia time, donor sex, donor ethnicity, donor BMI in both groups. Patients who received liver transplantation from donor age >65 had lower HCV infection (20% vs 41%), lower MELDNa score (19±6 vs 21±9), and lower donor HCV-positive graft (3% vs 13%) [Table 1]. Recipients of donor age ≥65 had similar outcomes including 1-year patient survival (96% vs 92%, p = NS), 1-year graft survival (93% vs 90%, p =NS), overall patient survival (94% vs 86%, p =NS) and overall graft survivals (90% vs 84%, p=NS) comparing to recipients of donor age <65, respectively [Table 2 and Figure 1].1014_A Figure 1. Baseline charecteristicsConclusion: In our study, careful allocation of grafts from older donors to appropriate recipients resulted in excellent 1-year and longer-term patient and graft survival comparable with outcomes in recipients from donor grafts age <65 years. Increasing utilization of grafts from older donors can expand the donor pool to decrease the national organ donor shortage.1014_B Figure 2. Results1014_C Figure 3. Kaplan Meier survival graphs

Hemoderivates Transfusion Differences Between Recipients of Liver Grafts from Donors After Uncontrolled Cardiac Death (uDCD) and Brain Death Donors (DBD)

Introduction The scarcity of grafts for liver transplantation (LT) from brain death donors (BDD), as well as the increasing mortality on waiting list have led us to look for other alternatives to achieve more liver grafts, being those from controlled and uncontrolled cardiac death (uDCD) the most attractive sources. However, intraoperative bleeding during LT has been higher when using uDCD donors, also related with higher morbi-mortality and lower patient and graft survival. Our aim is to compare the necessity of hemoderivates in uDCD and DBD groups. Materials and Methods Between January 2006 and December 2016 we performed 783 LT in adult recipients, excluding retransplants or patients undergoing OLT for acute liver failure. Liver grafts from uDCD donors (Group A) were used in 75 patients, and livers from BDD donors (Group B) were used in 708 patients. Results The mean age in group A was 59±8 years vs B 55±10 years in Group B (p=0.000). There were no significant differences in terms of sex, BMI and Child score. HCV cirrhosis was the indication for LT in 60% of cases in Group A vs 50.2% in group B (p=0.541). Hepatocellular carcinoma was present in 54.7% of patients in group A vs 38.9% in Group B (p=0.07). The mean of MELD score was 14.4±5 in Group A vs 14.5±6 in Group B (p=NS).The mean ICU stay was 6.8±7 days in Group A versus 6.3±9 days in group B (p=0.638). The mean transfusion of units of hemoderivates was as follows: 1) Packed red blood cells (PRBC): 12.3±13 units in Group A vs 8.6±10 Group B (p=0.008). 2) Fresh frozen plasma (FFP): 16.2±12 units in group A vs 10.7±8.8 in Group B (p=0.000). 3) Platelets: 2.29±2 units in group A vs 1.7±2 in group B (p=0.014). Using a logistic regression for multiple predictor variables, the only two factors with statistical significance related with MBT (>6 units of RBC) were uDCD condition (OR 2.3; CI 95%: 1.2-4.9; p=0.024), and higher Meld score (OR 2.75; CI 95%: 1.7-4.4; p=0.000) Survival at 1, 3 and 5 years was 81.3%, 70.2% and 68.6%, respectively, in group A vs 89%, 83.7% and 78.8%, respectively, in Group B (p= 0.070) Discussion. Conclusion The use of liver grafts from uDCD donors is associated with increased necessity of transfusion of hemoderivates in comparison with the use of BDD donors.

Assistance circulatoire et transplantation d’organes thoraciques chez l’enfant

Extracorporeal life support and heart and/or lung transplant are the last resort in children with end-stage cardiac and/or pulmonary failure and short-term life threaten. Currently, circulatory support is used as a bridge to recovery or as a bridge to transplant but not as a destination therapy. The Excor Berlin Heart is the long-lasting external pneumatic ventricular assist system that is currently available from infancy to adulthood. Long-term prognosis after pediatric cardiac and/or pulmonary transplant is conditioned by the occurrence of graft failure, coronary disease of the cardiac graft, viral infections and bronchiolitis obliterans of the pulmonary graft, the incidence of which increase with time. The scarcity of grafts and the risk of acute rejection due to lack of compliance with immunosuppressive treatment require the transplant specialized teams to choose the best candidates according to psychosocial and biological criteria. The next expected developments concern mainly long-term ventricular assistance with systems that allow for greater autonomy and a return to the child's home.

Corneal blindness and current major treatment concern-graft scarcity.

According to World Health Organization, the global prevalence of blindness in 2010 was 39 million people, among which 4% were due to corneal opacities. Often, the sole resort for visual restoration of patients with damaged corneas is corneal transplantation. However, despite rapid developments of surgical techniques, instrumentations and immunosuppressive agents, corneal blindness remains a prevalent global health issue. This is largely due to the scarcity of good quality corneal grafts. In this review, the causes of corneal blindness, its major treatment options, and the major contributory factors of corneal graft scarcity with potential solutions are discussed.

Influence of Deceased Donor and Pretransplant Recipient Parameters on Early Overall Kidney Graft-Survival in Germany.

Background. Scarcity of grafts for kidney transplantation (KTX) caused an increased consideration of deceased donors with substantial risk factors. There is no agreement on which ones are detrimental for overall graft-survival. Therefore, we investigated in a nationwide multicentre study the impact of donor and recipient related risks known before KTX on graft-survival based on the original data used for allocation and graft acceptance. Methods. A nationwide deidentified multicenter study-database was created of data concerning kidneys donated and transplanted in Germany between 2006 and 2008 as provided by the national organ procurement organization (Deutsche Stiftung Organtransplantation) and BQS Institute. Multiple Cox regression (significance level 5%, hazard ratio [95% CI]) was conducted (n = 4411, isolated KTX). Results. Risk factors associated with graft-survival were donor age (1.020 [1.013–1.027] per year), donor size (0.985 [0.977–0.993] per cm), donor's creatinine at admission (1.002 [1.001–1.004] per µmol/L), donor treatment with catecholamine (0.757 [0.635–0.901]), and reduced graft-quality at procurement (1.549 [1.217–1.973]), as well as recipient age (1.012 [1.003–1.021] per year), actual panel reactive antibodies (1.007 [1.002–1.011] per percent), retransplantation (1.850 [1.484–2.306]), recipient's cardiovascular comorbidity (1.436 [1.212–1.701]), and use of IL2-receptor antibodies for induction (0.741 [0.619–0.887]). Conclusion. Some donor characteristics persist to impact graft-survival (e.g., age) while the effect of others could be mitigated by elaborate donor-recipient match and care.

Split-Liver Full-Left Full-Right: Proposal for an Operative Protocol

IntroductionWorldwide, organ shortage is a major limiting factor to transplantations. One possible way to face graft scarcity is splitting full livers into hemilivers; this procedure would allow transplantation in 2 adult recipients with the use of a single organ from a deceased donor. ObjectiveThe goal of this study was to describe an adult-to-adult split liver operative protocol and share it between centers interested in exploring this procedure. Materials and MethodsA literature review was first conducted to elaborate on the present protocol; second, selection criteria for suitable deceased donors were identified. The technical aspects of performing the procurement were also analyzed; finally, the recipient selection criteria and the transplantation criteria were determined. ResultsThe donor characteristics should be consistent with the following: age ≤55 years; weight ≥70 kg; body mass index <28 kg/m2; intensive care unit stay <7 days; sodium level <160 mEq/L if the intensive care unit stay is >2 days; maximum transaminase value 3 times normal; hemodynamic stability; negative for hepatitis B surface antigen, hepatitis C virus, and human immunodeficiency virus; macrosteatosis <20%; macroscopic adequacy; and absence of anatomic anomalies requiring complex reconstruction. The procurement hospital should provide the preoperative computed tomography scan, liver dissector, and the intraoperative ultrasound. Indication for in situ or ex situ splitting depends on the hepatic vein outflow anatomy. Graft-to-recipient weight ratio should be ≥1%, and the graft-to-recipient spleen size ratio should be ≥0.6. United Network for Organ Sharing status 1 and 2A recipients are excluded, as are patients with transjugular intrahepatic portosystemic shunts. Hemiliver transplants are performed as in living-donor liver transplantation, and portal hyperflow is corrected by splenic artery ligation, splenectomy, and portal infusion of vasoactive drugs. ConclusionsThe present protocol was proposed to test the validity of the full-left full-right split liver procedure. A retrospective analysis found that 130 transplantations were suitable for this procedure according to the present protocol in the period January 1, 2008, through December 31, 2011 (65 donors). We believe that these numbers could be greatly increased once this procedure is proven feasible and safe within the proposed criteria.

Results of Clinical Lung Transplant From Uncontrolled Non-Heart-Beating Donors

The scarcity of grafts for lung transplant and the growing number of candidates expecting an organ has led to an increase of deaths in patients waiting for lung transplantation. Non-heart-beating donors (NHBD) represent a promising source of grafts for those who are involved in clinical lung transplantation. We present the results of our series of 17 out-of-hospital NHBD lung transplantations performed since 2002. We have collected data from 17 donors and recipients involved in NHBD lung transplants since 2002, as well as data referring to the type of procedure and peri-operative events. We describe the incidence of post-operative complications with special attention to primary graft disfunction (PGD), bronchial healing, bronchiolitis obliterans syndrome (BOS), and survival. We used Kaplan-Meier method to obtain the survival curve. G2-G3 PGD was reported in 9 patients (53%), with a complete restoration of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio in 170 hours for G2 and 168 hours for G3. There were no deaths directly related to PGD. Acute rejection was detected in 7 patients (41%), 4 of which exceeded grade 1. The incidence of BOS after transplantation was 1 (7%) of 14 patients during the first year, 2 (11%) of 9 in the second year, and 2 (50%) of 4 in the third year. Hospital mortality rate was 17%. The survival rates were 82% at 3 months, 69%, at 1 year, and 58% at 3 years. Mid-term results confirm the adequacy of uncontrolled NHBD as a promising complementary source of lung donors for clinical transplant.

IMPACT OF ADULT-TO-ADULT LIVING DONOR LIVER TRANSPLANTATION PROGRAM ON PATIENTS SURVIVAL: A FRENCH 5 YEAR SINGLE CENTER EXPERIENCE

A152 Aims: In France, the number of liver transplant patients directly depends on cadaveric graft procurement. Waiting time before liver transplantation (LT) dramatically increased during the past recent years, because of graft scarcity and of an increasing number of candidates. This situation led us to start an adult-to-adult living donor liver transplantation (AALDLT) program in 1998 in our center. The aim of this retrospective study was to compare the outcome of all adult patients put on the waiting list between 1998 and 2003 with respect of the graft used: cadaveric vs living donor. Patients and Methods: Between January 1998 and September 2003, 430 patients were put on waiting list in our center. AALDLT was performed in 32 cases (7.4%). This population was compared to the group of 266 adults who had had cadaveric LT (CLT) according to clinical and biological parameters at the time of listing, on the waiting list. One year survival from the time being on the waiting list and after LT was assessed for each group. Results: Comparison of patients with AALDLT and CLT is summarized in the Table.Figure* Significant difference Conclusion: Our results strongly suggest that an adult-to-adult living donor LT is efficient and, is able to improve the access to LT by reducing the waiting time and pre-transplant mortality. Moreover, patient survival was excellent in spite of their worse condition compared with that of patients having CLT.