Allogeneic Hematopoietic Stem Cell Transplantation After Prior Lung Transplantation for Hereditary Pulmonary Alveolar Proteinosis: A Case Report

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, post-lung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-disease (PAP) effect, and thus could improve long-term outcome. We describe the successful long-term post-transplant outcome of a unique case of end-stage respiratory failure due to hereditary PAP-induced pulmonary fibrosis, successfully treated by bilateral lung transplantation and subsequent allogeneic hematopoietic stem cell transplantation. Our report supports treatment with serial lung and hematopoietic stem cell transplantation to improve quality of life and prolong survival, without PAP recurrence, in selected patients with end-stage hereditary PAP

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Organ donation and transplantation statistics in Belgium for 2012 and 2013.

Background: The 2012 and 2013 solid organ transplantation statistics were presented during the annual meeting of the Belgian Transplant Society. Methods: All data presented were collected from Eurotransplant International Foundation and/or from all individual Belgian transplant centers. Results: It was demonstrated that the highest number of deceased donors detected (1310) from which 47.8% were an effective organ donor that corresponded to 29 per million inhabitants (pmi) in 2012 and 27.4 pmi in 2013. Out of 626 effective deceased organ donors, 491 (79%) were donors after brain death (DBD) and 135 (21%) donors after circulatory death (DCD), respectively. The majority (125/135; 93%) of DCD donors were DCD Maastricht category III donors and there were 7 (5%) donations following euthanasia. Family refusal tended to be lower for DCD (10.4%) compared to DBD donors (13.4%). Despite the increasing DCD donation rate, DBD donation remains stable in Belgium. The donor age is still increasing, reaching a median age of 53 years (range 0–90). Spontaneous intracranial bleeding (39.3%) and cranio-cerebral trauma (25%) remained the most frequent reasons of death. The number of living related kidney transplantations (57 in 2012 and 63 in 2013) followed the international trend albeit in Belgium it is still very limited. Nevertheless this activity could explain that the number of patients waiting for kidney transplantation (770) reached an absolute minimum in 2013. Except the reduced waiting list for lung transplantation (from 119 patients in 2011 to 85 in 2013), the waiting list remained stable for the other organs but almost 200 patients still died while on the waiting list. Conclusions: Belgium demonstrated the highest number of effective organ donors that corresponded to 29 per million inhabitants (pmi) in 2012 and 27.4 pmi in 2013. Thus far, and in contrast with other countries, there is no erosion of DBD in the DCD donor organ pool, but it is the important responsibility of all transplant centers and donor hospitals to avoid a substitution from DBD by DCD donors. Every year, the national organ donation and solid organ transplantation statistics are presented during the annual meeting of the Belgian Transplant Society

Donor categories: heart-beating, non-heart-beating and living donors; evolution within the last 10 years in UZ Leuven and Collaborative Donor Hospitals

Over the past 10 years, the University Hospitals Leuven and their group of Collaborative Donor Hospitals (~20) have tried to maximize their contribution to the national and Eurotransplant donor pool. In this time period, 1042 potential donors and 703 effective donors were coordinated and their organs allocated through Eurotransplant. This activity represented ~30% of the national donor pool and ~32% of the national organ pool. For Belgium, the nonheart- beating donor activity represented 11.38% of all donors in 2006. Since 1997, 167 potential live donors have been screened in our center. Of these, 48 transplants (28.74%) (39 kidneys - 9 livers) have been performed. A boost of screened candidates was seen over the last 3 years, with a 500% increase of records being evaluated. Although the Belgian live donation activity remains one of the lowest in the world, there has been a clear increase over the last 3 years with about 10% of all kidney transplant activity originating now from live donors

A retrospective database analysis to evaluate the potential of ex vivo lung perfusion to recruit declined lung donors

Ex vivo lung perfusion (EVLP) is currently used for both standard and extended-criteria donor (ECD) lungs. To enlarge the donor pool, we might have to extend the threshold for ECD donation. The purpose of this study was to estimate how many additional ECD lungs could be recruited by EVLP. We reviewed all multi-organ donors (MODs) from our collaborative donor hospitals (January 2010-June 2015). All unused lung donors were categorized using registered donor data and evaluated by two independent investigators to identify which lungs could be transplanted after EVLP. 584 MODs were registered at our transplant center. 268 (45.9%) were declined as lung donor at the moment of registration, and 316 (54.1%) were considered as a donor for lung transplantation. In the latter, lungs from 220 (37.7%) donors were transplanted and 96 donors (16.4%) were not. We identified 78 of 364 declined donors (21.4%) whose lungs could potentially become transplantable after EVLP. With this retrospective database analysis of unused lung donors, we identified a large potential for EVLP to further increase the donor pool in transplant centers where the majority of donor lungs are already extended.status: publishe

What is the limiting factor for organ procurement in Belgium: donation or detection ? What can be done to improve organ procurement rates?

In trying to overcome the growing gap between demand and offer of organs for transplantation, solutions are usually searched for by comparing successful and unsuccessful models in different countries. In particular, one element in the more successful countries such as for instance presumed consent, or one element in the less successful countries such as for instance refusal by relatives, are seen as possible reasons for these differences. This article tackles the problem of organ donor shortage through a new multi-level approach. Organ donation can indeed be analyzed on three different levels : the macro-level, the meso-level and the micro-level. The macro-level refers to the governmental structure where legislation, policies and funding are three essential elements necessary to make donation possible. The meso-level refers to the health care organization and the professionals who surround the process of organ donation and transplantation. Facilitating this process through standardized protocols and improving detection of organ donors are the two major elements. The micro-level refers to the individual believes and personal attitudes towards organ donation. This new multi-level approach gives a thorough and complete analysis of problems and allows to propose potential solutions to try to overcome the chronic organ shortage

Abdominal Transplant Surgery and Transplant Coordination University Hospitals Leuven 1997-2007: an overview

The transplant surgery and transplant coordination department was created in 1997 to meet up with the demand of the growing abdominal transplant surgery and organ procurement activity at the University Hospitals in Leuven. Since then, the procurement activity has increased and is currently distributed within the University Hospital Gasthuisberg and a network of approximately 25 collaborative hospitals. The profile of the donors has changed with older donors and more co-morbidity factors (obesity, hypertension, etc.). This donor activity represents approximately 30% of the national donor pool. Over the last 10 years, more than 1100 kidneys, more than 500 livers, approximately 50 pancreas, and 5 intestines have been transplanted in both adults and children. One year survival equal to- or exceeding 90% has been achieved for all abdominal organs and this compares favorably with international registries. More than 40 multi-visceral transplants {liver in combination with abdominal (kidney, pancreas, intestine) or thoracic (heart, double lung, heart-lung) organs} have been performed with results equivalent to isolated liver transplants and very little immunological graft loss (probably due to the immunoprotective effect of the liver). A live donation program was started for the kidney (40 cases) and for the liver (10 cases) in adults and children and no surgical graft loss has been seen so far. Introduction of new machine perfusion systems (and development of donor protocols) has made it possible to restart a non-heart-beating donor program for kidney transplantation. Experimental demonstration that livers tolerate short periods of warm ischemia has also allowed to start liver transplantation from non-heart-beating donors. In the future, machine perfusion of livers, viability testing, and biological modulation are likely to widen the use of marginal livers for transplantation and improve the results. An immunomodulatory protocol proven in the lab to induce the development of regulatory T cells has been applied clinically to 5 consecutive intestinal transplants. All 5--at the time of writing--have been rejection-free and have achieved nutritional independence. Continuous research and development is warranted to increase the organ donor pool (currently the solely limiting factor of transplantation) and to optimize long-term graft and patient outcome

Does mucosal inflammation drive recurrence of primary sclerosing cholangitis in liver transplantion recipients with ulcerative colitis?

Contains fulltext : 220062.pdf (Publisher’s version ) (Closed access)BACKGROUND: Liver transplantation remains the only effective evidence based treatment for advanced primary sclerosing cholangitis. However, recurrence of disease occurs in approximately 18%. AIMS: This study aimed to assess risk factors of recurrence of primary sclerosing cholangitis. METHODS: A retrospective cohort study was performed on patients undergoing transplantation for recurrence of primary sclerosing cholangitis in two academic centers (Leuven, Belgium and Leiden, The Netherlands). Besides other risk factors, the degree of mucosal inflammation was assessed as a potential risk factor using histological Geboes scores. RESULTS: 81 patients were included, of which 62 (76.5%) were diagnosed with ulcerative colitis. Seventeen patients (21.0%) developed rPSC during a median follow-up time of 5.2 years. In a subset of 42 patients no association was found between the degree of mucosal inflammation and recurrence, using both original Geboes scores and multiple cut-off points. In the total cohort, cytomegaloviremia post-transplantation (HR: 4.576, 95%CI 1.688-12.403) and younger receiver age at time of liver transplantation (HR: 0.934, 95%CI 0.881-0.990) were independently associated with an increased risk of recurrence of disease. CONCLUSION: This study found no association between the degree of mucosal inflammation and recurrence of primary sclerosing cholangitis. An association with recurrence was found for cytomegaloviremia post-liver transplantation and younger age at time of liver transplantation

Practice and challenges for organ donation after medical assistance in dying: A scoping review including the results of the first international roundtable in 2021

The procedure combining medical assistance in dying (MAiD) with donations after circulatory determination of death (DCDD) is known as organ donation after euthanasia (ODE). The first international roundtable on ODE was held during the 2021 WONCA family medicine conference as part of a scoping review. It aimed to document practice and related issues to advise patients, professionals, and policymakers, aiding the development of responsible guidelines and helping to navigate the issues. This was achieved through literature searches and national and international stakeholder meetings. Up to 2021, ODE was performed 286 times in Canada, the Netherlands, Spain, and Belgium, including eight cases of ODE from home (ODEH). MAiD was provided 17,217 times (2020) in the eight countries where ODE is permitted. As of 2021, 837 patients (up to 14% of recipients of DCDD donors) had received organs from ODE. ODE raises some important ethical concerns involving patient autonomy, the link between the request for MAiD and the request to donate organs and the increased burden placed on seriously ill MAiD patients