https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/lt.20663

Living Donor Liver Transplantation - Adult Donor Outcomes: A Systematic Review

: Background: The acceptance and application of the concept that brain death is a valid determination of death is the central issue in organ donation. However, whether attitude to brain death of health care professionals influences the organ procurement process has not been systematically studied.

Methods:  Questionnaires were distributed to health care professionals involved in the organ procurement process (intensive care, internal medicine, emergency room, anesthesia) in all hospitals in Israel. Attitude to brain death (defined as positive if the respondent accepted brain death as a valid determination of death, negative or do not know) and level of comfort in performing key donor-related tasks were analyzed.

Results:  A total of 2366 completed questionnaires were returned (629 doctors and 1737 nurses; response rate 60.3%). Overall, 78.9% of respondents had a positive attitude to brain death. This was significantly associated with increasing age, higher professional status and was most prevalent amongst intensive care unit staff (p < 0.001 for all variables). These respondents felt significantly more comfortable informing the transplant coordinator of a potential donor, explaining brain death to the family, raising the subject of organ donation, approaching the family about donation and providing support to the grieving family. In addition, they believed the transplant coordinator should be involved early in the donation process.

Conclusions:  The understanding and acceptance of brain death as a valid determination of death was associated with a positive effect on the level of comfort of health care professionals in performing key donor-related tasks. Reinforcing a positive attitude to brain death among health care professionals may facilitate the procurement process.

Attitude of health care professionals to brain death: influence on the organ donation process.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-6143.2012.04138.x

Continuously Evaluating Performance in Deceased Donation: The Spanish Quality Assurance Program

New indications for organ transplantation combined with a stagnating number of available donor grafts have severely lengthened the waiting list for almost all types of transplantations. This has led to a renewed interest in non-heart beating (NHB) donation, as a possible solution to bridge the gap between supply and demand. In this review, we present an overview of current NHB donation practice, outcome, existing problems and future perspectives. We focus on possible improvements in donor management, recipient care and new methods of organ preservation that may be better suited for these marginal organs. Successful institution of NHB protocols depends on adapting current transplantation practice at all levels, which is one of the greatest challenges for researchers and professionals in this interesting re-emerging field.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-2277.2007.00455.x

Non-heart beating organ donation: overview and future perspectives

To investigate on the impact of Critical Care (CC) staffs' attitudes to donation, their acceptance of the brain death (BD) concept, their confidence with donation-related tasks and educational needs on national donation rates. Donor Action (DA) Hospital Attitude Survey (HAS) data were collected from 19 537 CC staff in 11 countries, including personal attitudes to donation, self-reported knowledge, involvement and comfort levels with donation-related tasks and educational requirements. Countries' donation performance was expressed as Procurement Efficiency Index (PEI) (organs procured and transplanted/deaths from eligible causes). National PEI rates correlated well with CC staffs' average support to donation (R = 0.700, P = 0.014), acceptance of the BD concept (R = 0.742, P = 0.007), confidence levels (R = 0.796, P = 0.002) and average educational requirements with donation-related tasks (R = -0.661, P = 0.025). Nurses reported significantly lower positive attitudes (P < 0.0001), acceptance of the BD concept (P < 0.0001), comfort levels (P < 0.0001) and requested more education (P = 0.0025) than medical staff members. DA's HAS is a powerful, standardized tool to assess CC staffs' attitudes and donation-related skills in different environments. Measures to improve countries' donation performance should focus on guidance and education of CC staff so as to ensure that all practitioners have sufficient knowledge and feel comfortable with donation-related issues.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-2277.2010.01065.x

Critical Care staffs' attitudes, confidence levels and educational needs correlate with countries' donation rates: data from the Donor Action database

Background A major problem in the field of transplantation is the persistent shortage of donor organs and tissues for transplantation. This study was initiated to (1) chart the donor potential for organs and tissue in The Netherlands and (2) to identify factors influencing whether donation is discussed with next of kin. Methods. A registration form was constructed to obtain information at time of death of patients about the demographic characteristics, diagnosis, and medical suitability for donation. A prospective study was conducted among 11 hospitals in The Netherlands that gathered 4,877 filled-in forms equaling 8% to 10% of the people dying in a hospital in The Netherlands per year. Results. In the year of the study, organs were retrieved from 22 donors and tissues from 264 donors in the 11 hospitals. The organ potential is estimated at a maximum of 38.7 per million population per year. A mere 5% of the physicians got a 100% score on criteria and contraindications for donation. Factors of influence on receiving consent for donation were the will of the donor, using a protocol, giving verbal information to the relatives, and presence of the partner of the deceased patient. For 26% of the potential tissue donors and 69% of the potential organ donors, donation was discussed with the relatives. Consent for tissue donation was obtained in 27%, and consent for organ donation was obtained in 60%. Conclusions. In The Netherlands, when taking into account current refusal percentages, 320 to 360 organ donations and 5,800 tissue donations could be effectuated if organ donation is posed to all possible donors. For this, knowledge of medical criteria and contraindications for donation by the physicians and their willingness to discuss donation with next of kin must be improved.

Shortage of donation despite an adequate number of donors: A professional attitude?

Pulmonary graft-versus-host disease and chronic lung allograft dysfunction: two sides of the same coin?

Primary graft dysfunction (PGD) is the clinical syndrome of acute lung injury after lung transplantation (LTx). However, PGD is an umbrella term that encompasses the ongoing pathophysiological and -biological mechanisms occurring in the lung grafts. Therefore, we aim to provide a focused review on the clinical, physiological, radiological, histological and cellular level of PGD. PGD is graded based on hypoxemia and chest X-ray (CXR) infiltrates. High-grade PGD is associated with inferior outcome after LTx. Lung edema is the main characteristic of PGD and alters pulmonary compliance, gas exchange and circulation. A conventional CXR provides a rough estimate of lung edema, while a chest computed tomography (CT) results in a more in-depth analysis. Macroscopically, interstitial and alveolar edema can be distinguished below the visceral lung surface. On the histological level, PGD correlates to a pattern of diffuse alveolar damage (DAD). At the cellular level, ischemia-reperfusion injury (IRI) is the main trigger for the disruption of the endothelial-epithelial alveolar barrier and inflammatory cascade. The multilevel approach integrating all PGD-related aspects results in a better understanding of acute lung failure after LTx, providing novel insights for future therapies.

/pdf/a-focused-review-on-primary-graft-dysfunction-after-clinical-5kyjn4kj.pdf

A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

Abstract Alterations in the brain’s oxytocinergic system have been suggested to play an important role in the pathophysiology of autism spectrum disorder (ASD), but insights from pediatric populations are sparse. Here, salivary oxytocin was examined in the morning (AM) and afternoon (PM) in school-aged children with ( n = 80) and without ( n = 40) ASD (boys/girls 4/1), and also characterizations of DNA methylation (DNAm) of the oxytocin receptor gene ( OXTR ) were obtained. Further, cortisol levels were assessed to examine links between the oxytocinergic system and hypothalamic-pituitary-adrenal (HPA) axis signaling. Children with ASD displayed altered (diminished) oxytocin levels in the morning, but not in the afternoon, after a mildly stress-inducing social interaction session. Notably, in the control group, higher oxytocin levels at AM were associated with lower stress-induced cortisol at PM, likely reflective of a protective stress-regulatory mechanism for buffering HPA stress activity. In children with ASD, on the other hand, a significant rise in oxytocin levels from the morning to the afternoon was associated with a higher stress-induced cortisol release in the afternoon, likely reflective of a more reactive stress regulatory release of oxytocin for reactively coping with heightened HPA activity. Regarding epigenetic modifications, no overall pattern of OXTR hypo- or hypermethylation was evident in ASD. In control children, a notable association between OXTR methylation and levels of cortisol at PM was evident, likely indicative of a compensatory downregulation of OXTR methylation (higher oxytocin receptor expression) in children with heightened HPA axis activity. Together, these observations bear important insights into altered oxytocinergic signaling in ASD, which may aid in establishing relevant biomarkers for diagnostic and/or treatment evaluation purposes targeting the oxytocinergic system in ASD. 

/pdf/endogenous-oxytocin-levels-in-children-with-autism-egr23c0g.pdf

Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired clot resolution and in sustained fibrothrombotic obstruction of the pulmonary arterial bed remain poorly understood. Since defective angiogenesis correlated to defective clot resolution based on observations in surgical material from patients with CTEPH, we aimed to validate its crucial pathogenic role by intrathrombus inhibition of angiogenesis in a novel CTEPH rabbit model. Methods: We aimed to compare whether intrathrombus administration of an antifibrinolytic agent, tranexamic acid, or an inhibitor of angiogenesis, SU5416, would contribute to CTEPH progression. Both products were administered on a weekly basis by autologous clot embolization in rabbits. Right ventricular pressure was monitored by telemetry, right ventricular function by transthoracic echocardiography, and a complete pulmonary hemodynamic evaluation was obtained through right heart catheterization. Markers of inflammation, endothelial dysfunction, heart failure, and fibrinolysis were measured in plasma. Pulmonary vessel remodeling was analyzed by immunohistochemistry. Results: Impairing intrathrombus angiogenesis by repeatedly embolizing autologous blood clots containing SU5416 resulted in elevated mean pulmonary arterial pressure (38 mm Hg), increased indexed pulmonary vascular resistance, and enhanced right ventricular hypertrophy (80%, 1.9-fold, 36%, respectively, compared with rabbits embolized with clots containing an antifibrinolytic agent). This was caused by both obstruction of large pulmonary arteries with fibrothrombotic material and muscularization of pulmonary microvessels, and accompanied by inflammatory cell infiltration and increased circulating endothelin-1. Conclusions: The key role of angiogenesis-driven clot resolution was validated in a reliable small-animal model reproducing the major pathophysiological hallmarks of CTEPH.

Impairment of Angiogenesis-Driven Clot Resolution Is a Key Event in the Progression to Chronic Thromboembolic Pulmonary Hypertension: Validation in a Novel Rabbit Model

Linda Willems

Papers

Shortage of donation despite an adequate number of donors: A professional attitude?

Pulmonary graft-versus-host disease and chronic lung allograft dysfunction: two sides of the same coin?

A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation

Impairment of Angiogenesis-Driven Clot Resolution Is a Key Event in the Progression to Chronic Thromboembolic Pulmonary Hypertension: Validation in a Novel Rabbit Model