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Abstract Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg-1) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-α (p = 0.02), IL-6 (p = 0.001), IL-1β (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx.

Blood donation services seek new strategies to improve donor relationships and increase donor retention. In this study, we propose a novel strategy that employs appeals with feedback on the use of blood donors' past donations. We theorize that this feedback increases the perceived relationship investment and, subsequently, the quality of the relationship with the blood donation service, thereby increasing redonations. An online experiment shows the positive effect of past donation use appeals on donation intention and transmission through perceived relationship investment and relationship quality. Three field studies with Red Cross Blood Donation Services confirm the effectiveness of past donation use appeals on redonation behavior compared with thank-you appeals and with a future donation use appeal. Past donation use appeals are effective for retention purposes, especially for more experienced donors and when sent shortly after the donation. Such appeals also lead to higher reactivation rates of inactive donors. In addition to having practical implications, the study contributes to the relationship and nonprofit service literature. [ABSTRACT FROM AUTHOR]

Background: Improve the quality of donor coordination activities caused by an increased organ donation rate. The aim of this study was to assess the influence of organ donation coordinators' characteristics on rate of donation and family consent rate in Recognition Centers (RCs) and Organ Procurement Units (OPUs) in Iran by analyzing the organ procurement and transplantation data. Materials and methods: Based on a questionnaire, this retrospective study evaluated the number of confirmed brain deaths, family consent rate, organ recoveries, rate of expired brain death cases before and after family consent in Iran. Results: According to results, the overall family consent rate in the entire country is equal to 60.63%. The work experience had a significant effect on the number of procured organs (P < 0.004), death rate after family consent (P < 0.04), and eligible donor death before family consent (P < 0.03). The type of unit (RCs or OPUs) had significant difference on death after family consent (P < 0.023), the death before family consent (P < 0.014), the sum of procured organ (P < 0.04). Conclusion: The consent rate and donor management in the cases of brain death are unacceptable. The coordinators need training to increase their efficiency in terms of family approach and maintenance of brain death. Only by improving the level of family consent and increasing the coordinators' maintenance skills for brain death cases can the amount of organ donation in Iran be doubled to the current amount. [ABSTRACT FROM AUTHOR]

Eighty percent of brain‐dead (BD) organ donors develop hypotension and are frequently hypovolemic. Fluid resuscitation in a BD donor is controversial. We have previously published our 4‐h goal‐directed stroke volume (SV)‐based fluid resuscitation protocol which significantly decreased time on vasopressors and increased transplanting four or more organs. The SV was measured by pulse‐contour analysis (PCA) or an esophageal doppler monitor, both of which are invasive. Thoracic bioreactance (BR) is a non‐invasive portable technology that measures SV but has not been studied in BD donors. We performed a randomized prospective comparative study of BR versus PCA technology in our fluid resuscitation protocol in BD donors. Eighty‐four donors (53.1%) were randomized to BR and 74 donors to PCA (46.8%). The two groups were well matched based on 24 demographic, social, and initial laboratory factors, without any significant differences between them. There was no difference in the intravenous fluid infused over the 4‐h study period [BR 2271 ± 823 vs. PCA 2230 ± 962 mL; p =.77]. There was no difference in the time to wean off vasopressors [BR 108.8 ± 61.8 vs. PCA 150.0 ± 68 min p =.07], nor in the number of donors off vasopressors at the end of the protocol [BR 16 (28.6%) vs. PCA 15 (29.4%); p =.92]. There was no difference in the total number of organs transplanted per donor [BR 3.25 ± 1.77 vs. PCA 3.22 ± 1.75; p =.90], nor in any individual organ transplanted. BR was equivalent to PCA in clinical outcomes and provides a simple, non‐invasive, portable technology to monitor fluid resuscitation in organ donors. [ABSTRACT FROM AUTHOR]

Background and Objectives: Ferritin is commonly measured to evaluate iron stores in the body. Some countries have added or considered adding ferritin lower bounds to donor eligibility criteria. Ferritin is also elevated by inflammation. The main goal of this study is to estimate how different ferritin cut‐offs would affect the proportion of donors with a C‐reactive protein (CRP) level over 3 mg/L, which is the decision limit of the highest chronic cardiovascular risk. Materials and Methods: To simulate recruitment of new blood donors, we selected participants from two Finnish general population cohorts, namely FINRISK 1997 (n = 5369) and Health 2000 (n = 3278), that would likely fulfil the selection criteria of blood donation. We then calculated the proportion of individuals with high‐sensitivity CRP values above 3 mg/L, over a range of ferritin values. Results: We found that for several ferritin cut‐offs the proportion of potential donors with CRP > 3 mg/L would rise by a statistically significant amount. The trend was significant and similar for all subgroups but weaker for non‐menstruating women as well as men. Conclusion: Our results show that screening a population of potential blood donors with ferritin cut‐offs raises the number of people with CRP > 3 mg/L within the blood donor population. [ABSTRACT FROM AUTHOR]

Background: The role of nutrition in donor after brain deaths (DBDs) has yet to be adequately discussed. The primary aim of this study was to investigate whether the nutritional intake in the 48 h before organ retrieval may play a role on the graft functional recovery assessed with Model for Early Allograft Function (MEAF) Score. Methods: Single‐center retrospective study evaluating all liver transplants performed at the University Hospital of Udine from January 2010 to August 2020. Patients receiving grafts from DBD donors fed with artificial enteral nutrition in the 48 h prior to organ procurement (EN‐group) or who did not (No‐EN‐group). Caloric debt was calculated using the difference between the calculated caloric needs and the effective calories delivered through enteral nutrition. Results: Livers from EN‐group presented a lower mean MEAF score compared to the no‐EN‐group: 3.39 ± 1.46 versus 4.15 ± 1.51, respectively (p =.04). A positive correlation between caloric debt and the MEAF score was found within the overall population (r =.227, p =.043) as well as in EN‐group (r =.306, p =.049). Conclusions: Donor's nutritional intake in the final 48 h before organ procurement correlates with MEAF score, and nutrition probably plays a positive role on the functional recovery of the graft. Large future randomized controlled trials are needed to confirm this preliminary results. [ABSTRACT FROM AUTHOR]

Introduction: An increasing shortage of donor blood is expected, considering the demographic change in Germany. Due to the short shelf life and varying daily fluctuations in consumption, the storage of platelet concentrates (PCs) becomes challenging. This emphasizes the need for reliable prediction of needed PCs for the blood bank inventories. Therefore, the objective of this study was to evaluate multimodal data from multiple source systems within a hospital to predict the number of platelet transfusions in 3 days on a per-patient level. Methods: Data were collected from 25,190 (42% female and 58% male) patients between 2017 and 2021. For each patient, the number of received PCs, platelet count blood tests, drugs causing thrombocytopenia, acute platelet diseases, procedures, age, gender, and the period of a patient's hospital stay were collected. Two models were trained on samples using a sliding window of 7 days as input and a day 3 target. The model predicts whether a patient will be transfused 3 days in the future. The model was trained with an excessive hyperparameter search using patient-level repeated 5-fold cross-validation to optimize the average macro F2-score. Results: The trained models were tested on 5,022 unique patients. The best-performing model has a specificity of 0.99, a sensitivity of 0.37, an area under the precision-recall curve score of 0.45, an MCC score of 0.43, and an F1-score of 0.43. However, the model does not generalize well for cases when the need for a platelet transfusion is recognized. Conclusion: A patient AI-based platelet forecast could improve logistics management and reduce blood product waste. In this study, we build the first model to predict patient individual platelet demand. To the best of our knowledge, we are the first to introduce this approach. Our model predicts the need for platelet units for 3 days in the future. While sensitivity underperforms, specificity performs reliably. The model may be of clinical use as a pretest for potential patients needing a platelet transfusion within the next 3 days. As sensitivity needs to be improved, further studies should introduce deep learning and wider patient characterization to the methodological multimodal, multisource data approach. Furthermore, a hospital-wide consumption of PCs could be derived from individual predictions. [ABSTRACT FROM AUTHOR]

Problem definition: In the blood-donor-management problem, the blood bank incentivizes donors to donate, given blood inventory levels. We propose a model to optimize such incentivization schemes under the context of random demand, blood perishability, observation period between donations, and variability in donor arrivals and dropouts. Methodology/results: We propose an optimization model that simultaneously accounts for the dynamics in the blood inventory and the donor's donation process, as a coupled queueing network. We adopt the Pipeline Queue paradigm, which leads us to a tractable convex reformulation. The coupled setting requires new methodologies to be developed upon the existing Pipeline Queue framework. Numerical results demonstrate the advantages of the optimal policy by comparing it with the commonly adopted and studied threshold policy. Our optimal policy can effectively reduce both shortages and wastage. Managerial implications: Our model is the first to operationalize a dynamic donor-incentivization scheme, by determining the optimal number of donors of different donation responsiveness to receive each type of incentive. It can serve as a decision-support tool that incorporates practical features of blood supply-chain management not addressed thus far, to the best of our knowledge. Simulations on existing policies indicate the dangers of myopic approaches and justify the need for smoother and forward-looking donor-incentivization schedules that can hedge against future demand variation. Our model also has potential wider applications in supply chains with perishable inventory. Funding: This study was funded by the Singapore Management University through a research [Grant 20-C207-SMU-015] from the Ministry of Education Academic Research Fund Tier 1. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.1228. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). Donor risk factors for the development of PGD are incompletely characterized. Donor management goals (DMG) are predefined critical care endpoints used to optimize donors. We evaluated the relationship between DMGs as well as non-DMG parameters, and the development of PGD after HT. A cohort of HT recipients from 2 transplant centers between 1/1/12 and 12/31/19 was linked to their respective donors in the United Network for Organ Sharing (UNOS) DMG Registry (n = 1,079). PGD was defined according to modified ISHLT criteria. Variables were subject to univariate and multivariable multinomial modeling with development of mild/moderate or severe PGD as the outcome variable. A second multicenter cohort of 4,010 donors from the DMG Registry was used for validation. Mild/moderate and severe PGD occurred in 15% and 6% of the cohort. Multivariable modeling revealed 6 variables independently associated with mild/moderate and 6 associated with severe PGD, respectively. Recipient use of amiodarone plus beta-blocker, recipient mechanical circulatory support, donor age, donor fraction of inspired oxygen (FiO 2), and donor creatinine increased risk whereas predicted heart mass ratio decreased risk of severe PGD. We found that donor age and FiO 2 ≥ 40% were associated with an increased risk of death within 90 days post-transplant in a multicenter cohort. Donor hyperoxia at heart recovery is a novel risk factor for severe primary graft dysfunction and early recipient death. These results suggest that excessive oxygen supplementation should be minimized during donor management. [ABSTRACT FROM AUTHOR]

Despite clinical progress over time, a shortage of suitable donor organs continues to limit solid organ transplantation around the world. Lungs are the organs most likely to be assessed as unsuitable during donor management among all transplantable organs. Although the number of lung transplants performed in children is limited, death on the wait list remains a barrier to transplant success for many potential transplant candidates. Optimizing organ donor management can yield additional organs for transplant candidates. We accessed the Donor Management Goal (DMG) Registry to evaluate the efficiency and efficacy of donor management in the procurement of lungs for transplantation. Further, we stratified donors by age and compared pediatric age cohorts to adult cohorts with respect to attainment of donor management target goals and successful pathway to transplantation. We utilized recipient data from the Organ Procurement Transplantation Network (OPTN) to put this data into context. The DMG bundle consists of nine physiologic parameters chosen as end-points guiding donor management for potential organ donors. The number of parameters fulfilled has been regarded as an indication of efficacy of donor management. We noted a markedly lower number of organ donors in the pediatric age group compared to adults. On the other hand, the number of donors greatly exceeds the number of infants, children and adolescents who undergo lung transplantation. Organs transplanted per donor peaks in the adolescent age group. At initial donor referral, DMG bundle attainment is lower in all age groups and improves during donor management. With respect to oxygenation, there is less overall improvement in younger donors compared to older donors during donor management. When donors who yield lungs for transplantation are compared to those whose lungs were not transplanted, oxygenation improved more substantially during donor management. Furthermore, improved oxygenation correlated with the total number of organs transplanted per donor. In the face of continued wait list mortality on the pediatric lung transplant wait list, the number of young donors may not be a limiting factor. We believe that this dataset provides evidence that management of young pediatric donors is not as consistent or efficient as the management of older donors, potentially limiting the number of life-saving organs for pediatric lung transplant candidates. Across all ages, optimizing donor lung management may increase the potential to transplant multiple other organs. [ABSTRACT FROM AUTHOR]

Lung transplantation is a life-saving procedure in patients with end-stage lung disease. However, it inherently depends on the availability of donor organs. The selection of suitable lungs for transplantation, management of donors to minimize further injury and improve organ function, and safe procurement remain critical for successful transplantation. In this review, we provide an update on the current understanding of donor selection, management, and lung procurement.

Background and Objectives: ICMR conducted a multicentric trial “PLACID” that allowed COVID convalescent plasma (CCP) as an experimental drug for the management of moderate COVID-19 disease and the authors' institute was one of the participating centers. The efficacy of CCP in COVID-19 is still debatable. However, unlike therapeutic efficacy, there is not enough literature on issues and challenges faced by health-care institutions in donor recruitment, and the entire vein-to-vein process and approach of CCP transfusion. The authors would like to share their experiences, challenges faced, and their mitigation during the course of donor recruitment, screening, testing, apheresis donation, storage, inventory management, and issue and transfusion of CCP including the regulatory provisions, as their evolution. Methods: This retrospective study was conducted over a period of 7 months at a large tertiary care hospital in north India. Based on ICMR guidelines, the study analyzed the screening process and donation from all consecutive potential CCP donors. The study also identified various issues and challenges faced by the institute and how they were resolved. Results: Prospective donors registered at the blood center were 843. Majority were males (96.6%), first-time CCP donors (93%), age interval 31–45 years (52.2%), who had a history of mild COVID-19 symptoms (86.9%), and were home-quarantined (83.8%). The most common blood group was B positive (50.6%). Only 6.3% of donors were deferred due to the absence of anti-COVID-19 antibodies. Of 843, 705 selected CCP donors donated 1488 CCP units and six donors (0.8%) experienced mild adverse reactions. Challenges faced by authors included donor recruitment, lack of regulatory approval for plasmapheresis, revisions of COVID-specific selection criteria, no “anti-COVID-19 antibody” kit, and CCP inventory management. Conclusion: This study provides real-world comprehensive data on process management of CCP donors and their donations. This understanding of the process, its challenges, and their mitigation could be a template for any possible future pandemic.

Background: Understanding donor factors associated with successful lung transplantation (LTx) following donation after circulatory death (DCD) is important in optimizing donor management. In this study, we examined critical care and ventilatory factors associated with DCD LTx and allograft survival using a unique detailed donor management database., Methods: The Donor Management Goals national registry was queried for DCD donors between January 2016 and July 2023. The primary outcomes were DCD lung utilization and allograft survival. Multivariable modeling was used to assess factors associated with DCD LTx and allograft survival., Results: A total of 3,394 donors met inclusion criteria and were included. Transplantation occurred in 202 (6.0%) cases with 85.6% 1-year survival. DCD LTx was more likely to occur following cerebrovascular accidents compared to anoxia and from donors who achieved a targeted PaO 2 /FiO 2 (P/F) ratio at the time of organ allocation. Donor factors associated with decreased likelihood of LTx included increasing age, increasing INR, height greater than 168 cm, increasing hematocrit, and higher positive end-expiratory pressure (PEEP) at the time of organ allocation. Donor treatment with steroids and controlled mandatory ventilation, were associated with increased likelihood of graft failure at one year., Conclusions: Successful DCD LTx associates with potentially modifiable donor parameters, including targeted P/F ratio, PEEP, INR, and hematocrit. Additionally, careful consideration of steroid use and ventilator settings may be important for improving long-term graft function. These modifiable factors may inform strategies to increase DCD LTx and improve survival., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Current risk-adjusted models for predicting primary graft dysfunction (PGD) following lung transplantation (LTx) do not include bedside donor critical care data. Donor management goals (DMGs) represent predefined critical care endpoints aimed at optimizing multiorgan donor management. Here we sought to identify novel predictors to better understand the relationship between donor management and PGD following LTx., Methods: We used the national DMG registry to identify a cohort of LTx recipients linked to their respective donors between January 1, 2015, and March 1, 2023. Grade 3 PGD (PGD3) was defined according to modified International Society for Heart and Lung Transplantation criteria. Multivariable modeling was performed to identify risk factors for the development of PGD3., Results: A total of 2704 eligible patients were identified, of whom 643 (23.8%) developed PGD3. After multivariable modeling, the likelihood of PGD3 was greater with increasing donor age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.10 per 5-year change; P = .003), increasing donor serum pH at the time of authorization (OR, 1.14; 95% CI, 1.02-1.25 per 0.1-point increase; P = .016), donor history of cocaine use (OR, 1.34; 95% CI, 1.05-1.71; P = .020), and increased recipient central venous pressure (OR, 1.03; 95% CI, 1.01-1.06; P = .005). Recipients who received donor lungs in which the DMG for PF ratio was met had a lower likelihood of developing PGD3 (OR, 0.63; 95% CI, 0.46-0.86; P = .006)., Conclusions: This study leverages a novel detailed donor management database to identify factors associated with the development of PGD3. These factors may be used to recognize donors and recipients who may benefit from early interventions to improve short-term outcomes., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Abstract Background Brain death frequently induces hemodynamic instability and cardiac stunning. Impairments in cardiac performance are major contributors to hearts from otherwise eligible organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid-stimulating hormone) may contribute to hemodynamic instability, and replacement of thyroid hormone has been proposed as a means of improving stability and increasing hearts available for transplantation. Intravenous thyroxine is commonly used in donor management. However, small controlled trials have not been able to demonstrate efficacy. Methods This multicenter study will involve organ procurement organizations (OPOs) across the country. A total of 800 heart-eligible brain-dead organ donors who require vasopressor support will be randomly assigned to intravenous thyroxine for at least 12 h or saline placebo. The primary study hypotheses are that thyroxine treatment will result in a higher proportion of hearts transplanted and that these hearts will have non-inferior function to hearts not treated with thyroxine. Additional outcome measures are the time to achieve hemodynamic stability (weaning off vasopressors) and improvement in cardiac ejection fraction on echocardiography. Discussion This will be the largest randomized controlled study to evaluate the efficacy of thyroid hormone treatment in organ donor management. By collaborating across multiple OPOs, it will be able to enroll an adequate number of donors and be powered to definitively answer the critical question of whether intravenous thyroxine treatment increases hearts transplanted and/or provides hemodynamic benefits for donor management. Trial registration ClinicalTrials.gov NCT04415658 . Registered on June 4, 2020

With the continued deficit of available organs for transplantation, optimal care of the brain-dead and cardiac death donor is essential to optimize quality and quantity of precious organs. Anesthesiologists are a critical part of the perioperative surgical retrieval process, although individually, may rarely care for a donor. Prospective data to inform specific clinical practices is sparse although educational resources exist to guide anesthesiologists with ethical or clinical questions and protocols from intensive care units and organ procurement organizations serve as useful templates for maintenance of organ function. Pre-surgical resuscitation, optimization and homeostatic strategies should be continued into the operating room. Cautious titration of low dose anesthetic and analgesic agents may be required to blunt sympathetic and spinal reflexes but should not aggravate hypotension and muscle relaxation is recommended to facilitate surgical exposure. Anesthesiologists should be aware of procedural and pharmaceutical aspects of the donation process, including re-intubation of a deceased donor after death is confirmed when lung retrieval is planned.

Background: Previous studies that describe the negative association between temporary deferrals and donor return rates commonly come from settings where mechanisms are in place to win back lapsing donors. There is little evidence on the size and prevalence of this negative association in settings with no such retention activities. Study Design and Methods: We use data from more than 2 million donation attempts made at a blood collection agency in Brazil over a 26‐year period. We describe the distribution of deferrals across donor demographic and behavioral characteristics, and estimate multivariate survival analysis models with matched samples to measure the impact of deferrals on return rates. We control for sex, race, age, education, donation type, number of previous attempts, previous donations, and previous deferrals. We test for heterogeneous effects in interaction models with selected donor demographic and behavioral characteristics. Results: Temporary deferrals were associated with a 50% decrease in the likelihood of return. Although the effect was observed for all population subgroups and across the full length of the dataset, it varied in magnitude. The influence of deferrals was more negative among older donors and those reporting replacement motives, and less negative among more educated donors and those with a previous donation. Discussion: We found that temporary deferrals meaningfully harm donor careers in a setting where specific retention activities are absent. Although the effects are widespread across the population and persistent in time, there are also heterogeneities, which must be considered when designing interventions targeted at wining‐back specific groups of deferred donors. [ABSTRACT FROM AUTHOR]

Lung transplantation (LTx) is the definitive treatment for select progressive end-stage lung disease patients despite being on optimum medical therapy. Asian countries like China, Japan and India have started LTx programmes despite various odds and challenges. Some of these challenges seem to be unique to developing countries. We have elaborated the challenges of LTx in India and their proposed solutions and shared our experience in setting up a successful LTx programme. [ABSTRACT FROM AUTHOR]

Background: Delayed graft function (DGF) after kidney transplantation is a common occurrence and correlates with poor graft and patient outcomes. Donor characteristics and care are known to impact DGF. We attempted to show the relationship between achievement of specific donor management goals (DMG) and DGF. Methods: This is a retrospective case‐control study using data from 14 046 adult kidney donations after brain death from hospitals in 18 organ procurement organizations (OPOs) which were transplanted to adult recipients between 2012 and 2018. Data on DMG compliance and donor, recipient, and ischemia‐related factors were used to create multivariable logistic regression models. Results: The overall rate of DGF was 29.4%. Meeting DMGs for urine output and vasopressor use were associated with decreased risk of DGF. Sensitivity analyses performed with different imputation methods, omitting recipient factors, and analyzing multiple time points yielded largely consistent results. Conclusions: The development of DMGs continues to show promise in improving outcomes in the kidney transplant recipient population. Studies have already shown increased kidney utilization in smaller cohorts, as well as other organs, and shown decreased rates of DGF. Additional research and analysis are required to assess interactions between meeting DMGs and correlation versus causality in DMGs and DGF. [ABSTRACT FROM AUTHOR]

Background and Objectives: ICMR conducted a multicentric trial "PLACID" that allowed COVID convalescent plasma (CCP) as an experimental drug for the management of moderate COVID-19 disease and the authors' institute was one of the participating centers. The efficacy of CCP in COVID-19 is still debatable. However, unlike therapeutic efficacy, there is not enough literature on issues and challenges faced by health-care institutions in donor recruitment, and the entire vein-to-vein process and approach of CCP transfusion. The authors would like to share their experiences, challenges faced, and their mitigation during the course of donor recruitment, screening, testing, apheresis donation, storage, inventory management, and issue and transfusion of CCP including the regulatory provisions, as their evolution. Methods: This retrospective study was conducted over a period of 7 months at a large tertiary care hospital in north India. Based on ICMR guidelines, the study analyzed the screening process and donation from all consecutive potential CCP donors. The study also identified various issues and challenges faced by the institute and how they were resolved. Results: Prospective donors registered at the blood center were 843. Majority were males (96.6%), first-time CCP donors (93%), age interval 31-45 years (52.2%), who had a history of mild COVID-19 symptoms (86.9%), and were home-quarantined (83.8%). The most common blood group was B positive (50.6%). Only 6.3% of donors were deferred due to the absence of anti-COVID-19 antibodies. Of 843, 705 selected CCP donors donated 1488 CCP units and six donors (0.8%) experienced mild adverse reactions. Challenges faced by authors included donor recruitment, lack of regulatory approval for plasmapheresis, revisions of COVID-specific selection criteria, no "anti-COVID-19 antibody" kit, and CCP inventory management. Conclusion: This study provides real-world comprehensive data on process management of CCP donors and their donations. This understanding of the process, its challenges, and their mitigation could be a template for any possible future pandemic. [ABSTRACT FROM AUTHOR]

Abstract Background The quality of clinical care of brain-dead potential organ donors may help reduce donor losses caused by irreversible or unreversed cardiac arrest and increase the number of organs donated. We sought to determine whether an evidence-based, goal-directed checklist for donor management in intensive care units (ICUs) can reduce donor losses to cardiac arrest. Methods/design The DONORS study is a multicentre, cluster-randomised controlled trial with a 1:1 allocation ratio designed to compare an intervention group (goal-directed checklist for brain-dead potential organ donor management) with a control group (standard ICU care). The primary outcome is loss of potential donors due to cardiac arrest. Secondary outcomes are the number of actual organ donors and the number of solid organs recovered per actual donor. Exploratory outcomes include the achievement of relevant clinical goals during the management of brain-dead potential organ donors. The present statistical analysis plan (SAP) describes all primary statistical procedures that will be used to evaluate the results and perform exploratory and sensitivity analyses of the trial. Discussion The SAP of the DONORS study aims to describe its analytic procedures, enhancing the transparency of the study. At the moment of SAP subsmission, 63 institutions have been randomised and were enrolling study participants. Thus, the analyses reported herein have been defined before the end of the study recruitment and database locking. Trial registration ClinicalTrials.gov, NCT03179020 . Registered on 7 June 2017.

The authors recognise some limitations - particularly that patients making hypothetical decisions may act differently to a real decision, and that some included patients were post-transplant and may feel differently about risk compared to their own pre-transplant status. Donor management, patient preferences, kidney transplantation, randomised controlled trial, liver transplantation outcome Keywords: donor management; liver transplantation outcome; patient preferences; kidney transplantation; randomised controlled trial EN donor management liver transplantation outcome patient preferences kidney transplantation randomised controlled trial 1 3 3 01/05/23 20221201 NES 221201 To keep the transplantation community informed about recently published level 1 evidence in organ transplantation ESOT and the Centre for Evidence in Transplantation have developed the Transplant Trial Watch. [Extracted from the article]

Background: Brain death frequently induces hemodynamic instability and cardiac stunning. Impairments in cardiac performance are major contributors to hearts from otherwise eligible organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid-stimulating hormone) may contribute to hemodynamic instability, and replacement of thyroid hormone has been proposed as a means of improving stability and increasing hearts available for transplantation. Intravenous thyroxine is commonly used in donor management. However, small controlled trials have not been able to demonstrate efficacy.Methods: This multicenter study will involve organ procurement organizations (OPOs) across the country. A total of 800 heart-eligible brain-dead organ donors who require vasopressor support will be randomly assigned to intravenous thyroxine for at least 12 h or saline placebo. The primary study hypotheses are that thyroxine treatment will result in a higher proportion of hearts transplanted and that these hearts will have non-inferior function to hearts not treated with thyroxine. Additional outcome measures are the time to achieve hemodynamic stability (weaning off vasopressors) and improvement in cardiac ejection fraction on echocardiography.Discussion: This will be the largest randomized controlled study to evaluate the efficacy of thyroid hormone treatment in organ donor management. By collaborating across multiple OPOs, it will be able to enroll an adequate number of donors and be powered to definitively answer the critical question of whether intravenous thyroxine treatment increases hearts transplanted and/or provides hemodynamic benefits for donor management.Trial Registration: ClinicalTrials.gov NCT04415658 . Registered on June 4, 2020. [ABSTRACT FROM AUTHOR]

Organ transplantation is a life-saving intervention for patients suffering from end-stage organ failure, but it relies on the availability of donor organs. However, even when donors are available, the brain-dead organ donor is a clinically complex patient who presents many management challenges. Donor management with a goal of optimization of organ function is essential to maximizing the number of patients who can be helped by each individual donor. Thoughtful critical care management of the potential organ donor, with a focus on meeting donor management goals, can lead to improved donation outcomes. [ABSTRACT FROM AUTHOR]

Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5mg q4h) versus saline placebo during active donor management in 506 organ donors.The primary outcome was change in oxygenation arterial partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2] from enrollment to organ procurement.The albuterol (n¼260) and placebo (n¼246)groups were well matched for age, gender, ethnicity,smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p¼0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%,p¼0.44). Donors in the albuterol versus placebo groups were more likely to have the study drug dose reduced (13% vs. 1%, p

Background: The process of brain death (BD) leads to a pro-inflammatory state of the donor lung, which deteriorates its quality. In an attempt to preserve lung quality, methylprednisolone is widely recommended in donor lung management. However, clinical treatment doses vary and the dose-effect relation of methylprednisolone on BD-induced lung inflammation remains unknown. The aim of this study was to investigate the effect of three different doses methylprednisolone on the BD-induced inflammatory response.Methods: BD was induced in rats by inflation of a Fogarty balloon catheter in the epidural space. After 60 min of BD, saline or methylprednisolone (low dose (5 mg/kg), intermediate dose (12.5 mg/kg) or high dose (22.5 mg/kg)) was administered intravenously. The lungs were procured and processed after 4 h of BD. Inflammatory gene expressions were analyzed by RT-qPCR and influx of neutrophils and macrophages were quantified with immunohistochemical staining.Results: Methylprednisolone treatment reduced neutrophil chemotaxis as demonstrated by lower IL-8-like CINC-1 and E-selectin levels, which was most evident in rats treated with intermediate and high doses methylprednisolone. Macrophage chemotaxis was attenuated in all methylprednisolone treated rats, as corroborated by lower MCP-1 levels compared to saline treated rats. Thereby, all doses methylprednisolone reduced TNF-α, IL-6 and IL-1β tissue levels. In addition, intermediate and high doses methylprednisolone induced a protective anti-inflammatory response, as reflected by upregulated IL-10 expression when compared to saline treated brain-dead rats.Conclusion: We showed that intermediate and high doses methylprednisolone share most potential to target BD-induced lung inflammation in rats. Considering possible side effects of high doses methylprednisolone, we conclude from this study that an intermediate dose of 12.5 mg/kg methylprednisolone is the optimal treatment dose for BD-induced lung inflammation in rats, which reduces the pro-inflammatory state and additionally promotes a protective, anti-inflammatory response.

Prior studies have demonstrated associations between beta-adrenergic receptor (βAR) polymorphisms and left ventricular dysfunction-an important cause of allograft nonutilization for transplantation. We hypothesized that βAR polymorphisms predispose donor hearts to LV dysfunction after brain death. A total of 1043 organ donors managed from 2001-2006 were initially studied. The following βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/A (Gly16Arg) and β2AR 79C/G (Gln27Glu). In multivariable regression analyses, the β2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction 10 μg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between βAR SNPs and cardiac dysfunction in 364 donors managed from 2007-2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. βAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts.

IntroductionA majority of transplanted organs come from donors after brain death (BD). Renal grafts from these donors have higher delayed graft function and lower long-term survival rates compared to living donors. We designed a novel porcine BD model to better delineate the incompletely understood inflammatory response to BD, hypothesizing that adhesion molecule pathways would be upregulated in BD.MethodsAnimals were anesthetized and instrumented with monitors and a balloon catheter, then randomized to control and BD groups. BD was induced by inflating the balloon catheter and animals were maintained for 6 hours. RNA was extracted from kidneys, and gene expression pattern was determined.ResultsIn total, 902 gene pairs were differently expressed between groups. Eleven selected pathways were upregulated after BD, including cell adhesion molecules.ConclusionsThese results should be confirmed in human organ donors. Treatment strategies should target involved pathways and lessen the negative effects of BD on transplantable organs.

Background: The quality of clinical care of brain-dead potential organ donors may help reduce donor losses caused by irreversible or unreversed cardiac arrest and increase the number of organs donated. We sought to determine whether an evidence-based, goal-directed checklist for donor management in intensive care units (ICUs) can reduce donor losses to cardiac arrest.Methods/design: The DONORS study is a multicentre, cluster-randomised controlled trial with a 1:1 allocation ratio designed to compare an intervention group (goal-directed checklist for brain-dead potential organ donor management) with a control group (standard ICU care). The primary outcome is loss of potential donors due to cardiac arrest. Secondary outcomes are the number of actual organ donors and the number of solid organs recovered per actual donor. Exploratory outcomes include the achievement of relevant clinical goals during the management of brain-dead potential organ donors. The present statistical analysis plan (SAP) describes all primary statistical procedures that will be used to evaluate the results and perform exploratory and sensitivity analyses of the trial.Discussion: The SAP of the DONORS study aims to describe its analytic procedures, enhancing the transparency of the study. At the moment of SAP subsmission, 63 institutions have been randomised and were enrolling study participants. Thus, the analyses reported herein have been defined before the end of the study recruitment and database locking.Trial Registration: ClinicalTrials.gov, NCT03179020. Registered on 7 June 2017. [ABSTRACT FROM AUTHOR]

Rationale: Brain death (BD) precipitates cardiac dysfunction impairing the ability to transplant hearts from eligible organ donors. Retrospective studies have suggested that thyroid hormone may enhance myocardial recovery and increase hearts transplanted. We performed a randomized trial evaluating whether intravenous thyroxine (T4) improves cardiac function in BD donors with impaired ejection fraction (EF). Methods: All heart-eligible donors managed at a single-organ procurement organization (OPO) underwent protocolized fluid resuscitation. Those weaned off vasopressors underwent transthoracic echocardiography (TTE) within 12 hours of BD and, if EF was below 60%, were randomized to T4 infusion or no T4 for 8 hours, after which TTE was repeated. Results: Of 77 heart-eligible donors, 36 were weaned off vasopressors. Ejection fraction was depressed in 30, of whom 28 were randomized to T4 (n = 17) vs control (n = 11). Baseline EF was comparable (45%, interquartile range [IQR] 42.5-47.5 vs 40%, 40-50, P =.32). Ejection fraction did not improve more with T4 (10%, IQR 5-15 vs 5%, 0-12.5, P =.24), although there was a trend to more hearts transplanted (59% vs 27%, P =.14). This difference appeared to be accounted for by more donors with a history of drug use in the T4 group, who exhibited greater improvements in EF (15% vs 0% without drug use, P =.01) and more often had hearts transplanted (12 of 19 vs 1 of 9, P =.01). Conclusions: In this small randomized study of BD donors with impaired cardiac function, T4 infusion did not result in greater cardiac recovery. A larger randomized trial comparing T4 to placebo appears warranted but would require collaboration across multiple OPOs. [ABSTRACT FROM AUTHOR]

Background and objectives: The availability of blood and blood products is crucial for the provision of high‐quality hospital services. We analyse changes in whole blood donations, donors and their behaviour over 9 years at a large German teaching hospital. Materials and methods: A descriptive analysis using data from over 34 000 donors and 265 000 donations from a large university hospital's blood centre was conducted using data from July 2008 to December 2017. The analysis focussed on (a) whole blood donations and (b) donor characteristics and how they changed over time. We categorized donors into four categories according to their donation activity (First‐Time, Highly Active, Active and Reactivated). Results: We observed falling donations over time and that donors donated less frequently. Consequently, we show a downward trend in the number of Highly Active donors, whilst First‐Time donors remained stable. We also provide evidence that donors donated well below their capacity and that the blood type of donors appeared to be in line with the wider German donor population. Lastly, we show a sharp drop in the return rates of First‐Time donors over time. Conclusion: We recommend that Highly Active donors and former Highly Active donors are more carefully considered when planning donor engagement strategies and effort made in (at the very least) maintaining their donation activity. Our results in the context of the literature highlight the need for further research into the changing attitudes towards blood donation and prosocial activities. [ABSTRACT FROM AUTHOR]

Over the last decade, striking progress has been made in the field of organ transplantation, such as better surgical expertise and preservation techniques. Therefore, organ transplantation is nowadays considered a successful treatment in end-stage diseases of various organs, e.g. the kidney, liver, intestine, heart, and lungs. However, there are still barriers which prevent a lifelong survival of the donor graft in the recipient. Activation of the immune system is an important limiting factor in the transplantation process. As part of this pro-inflammatory environment, the complement system is triggered. Complement activation plays a key role in the transplantation process, as highlighted by the amount of studies in ischemia-reperfusion injury (IRI) and rejection. However, new insight have shown that complement is not only activated in the later stages of transplantation, but already commences in the donor. In deceased donors, complement activation is associated with deteriorated quality of deceased donor organs. Of importance, since most donor organs are derived from either brain-dead donors or deceased after circulatory death donors. The exact mechanisms and the role of the complement system in the pathophysiology of the deceased donor have been underexposed. This review provides an overview of the current knowledge on complement activation in the (multi-)organ donor. Targeting the complement system might be a promising therapeutic strategy to improve the quality of various donor organs. Therefore, we will discuss the complement therapeutics that already have been tested in the donor. Finally, we question whether complement therapeutics should be translated to the clinics and if all organs share the same potential complement targets, considering the physiological differences of each organ.

The objective of this mixed-methods study was to explore the experiences and perspectives of Transplant Nurses (TNs) in caring for related donors (RDs). In this mixed-methods study, both quantitative and qualitative data were collected from semi-structured interviews with seven TNs from two clinical hospitals. Closed and multiple-choice questions regarding the organisation of RD care were administered in addition to an in-depth exploration of TN experiences and perspectives of RD care. Interviews were audio-recorded, transcribed, and qualitative data was subjected to thematic analyses. The analysis identified 5 themes relating to RD care: managing complex family dynamics and ambivalence; concerns about RD psychological adjustment; identifying and correcting RD misperceptions; limited guidelines and structured processes; limited training for the role and access to supervision. Five themes were identified describing the barriers to delivering RD care: RDs unwilling to express their concerns; language; time constraints; medical priority of clinicians; biomedical focus of TNs. All TNs agreed they would like additional training in the psychosocial management of RDs. TNs identified key areas for improvement, including psychosocial support and educational material. Our results highlight the significant role of TNs in RD care, and underline issues specific to the current RD care environment. Lack of training for the role and limited guidelines addressing RD care management are key issues which may detrimentally affect RD care. The pivotal role of TNs must be acknowledged and supported by improving TN training and implementing clear guidelines for the management of RDs. The trial has been registered on the publicly accessible register: www.clinicaltrials.gov site with the identifier ACTRN12617000407392. • Despite the expansion of related donor transplants, guidelines for related donor care management are still lacking. • Transplant Nurses are well placed to provide holistic care but report lack of training to respond to challenges. • Common challenges include family conflict, donor ambivalence and distress after recipient death. • Communication skills training and development of referral pathways to access psychosocial care are needed. • Guidelines to promote consistency and strategies for responding to challenges should be a priority. [ABSTRACT FROM AUTHOR]

Background: We sought to analyze brain death interval and outcomes of pediatric cardiac transplantation using national registry data. Methods: We retrospectively evaluated a pediatric cohort from the UNOS registry from 2005 to 2014. We restricted the donor cohort to those with a primary central nervous system event as the cause of hospitalization. Brain death interval (BDI) was defined as the time between hospital admission and organ procurement. Primary outcomes were recipient and graft survival time. Logistical regression modeling was used for multivariable analysis. Results: The donor cohort included 2565 cases. Multivariable analysis demonstrated no relationship between BDI and recipient or graft survival time. For patient survival time, the lowest HR was 0.94 (0.63‐1.39), P = 0.531; for graft survival time, the lowest HR was 0.89 (0.53‐1.49), P = 0.563. We obtained similar results using a non‐restricted donor cohort. Conclusions: There was no clear relationship between BDI and recipient or graft survival after pediatric cardiac transplantation. [ABSTRACT FROM AUTHOR]

The effect of thyroid dysfunction on adverse outcomes has been studied in many different patient populations. The objective of this study was to investigate the effect of thyroid hormone supplementation of donors and recipients on postoperative outcomes after orthotopic heart transplantation. Retrospective. Single center, university hospital. Two-hundred and sixty-six consecutive patients undergoing heart transplantation. No interventions. Demographic, hemodynamic, and clinical characteristics; donor and recipient United Network for Organ Sharing scores; and information on thyroid hormone support of donors and recipients were recorded. During the median follow-up of 4.59 years (interquartile range 4.26-4.92 y), 70 patients (26.3%) died. After adjustments were made for the United Network for Organ Sharing score, recipients who were treated preoperatively with l-thyroxine had a lower risk for all-cause mortality (adjusted hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.06-0.98; p = 0.047) compared with recipients who were not treated with l-thyroxine. In addition, l-thyroxine treatment of donors was associated with a better recipient survival (HR 0.31, 95% CI 0.11-0.87; p = 0.025). Pretransplantation thyroid hormone supplementation of donors and recipients was associated with improved long-term survival after heart transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Rates of successful organ donation vary between otherwise comparable intensive care units (ICUs). The ICU staff have a unique perspective into the facilitators and barriers underlying this variation in successful deceased organ donation. Research Question: What do ICU staff perceive to be the most meaningful facilitators and barriers to deceased organ donation? Design: We designed and conducted a survey of all disciplines working in the ICU to ascertain the perceived facilitators and barriers to donation in an academic tertiary care hospital. Survey reliability was assessed using Cronbach α. Factor analysis was used to assess construct validity and identify potentially redundant survey items. Results: We had responses from 108 ICU staff, including nurses (n = 75), respiratory therapists (n = 14), physicians (n = 12), chaplains (n = 2), as well as social work, pharmacy, physiotherapy, and occupational therapy (n = 1 each). Perceived facilitators included availability of organ donation organization coordinators, explicit institutional support for donation, ICU staff culture toward donation, standardized order sets for donation, presence of ICU staff with donation experience, and bedside nurse presence at discussions about donation. Perceived barriers included ICU staff ruling out potentially suitable donors before consulting a donor coordinator, physician communication skills, low priority for organ donation among operating room staff, limited family understanding of patient prognosis and organ donation, and limited emotional readiness of families to discuss donation. Discussion: Several staff-perceived facilitators and barriers to deceased organ donation were identified in the ICU. Future research could identify strategies to promote these facilitators and overcome barriers. [ABSTRACT FROM AUTHOR]

Over the last decade, striking progress has been made in the field of organ transplantation, such as better surgical expertise and preservation techniques. Therefore, organ transplantation is nowadays considered a successful treatment in end-stage diseases of various organs, e.g. the kidney, liver, intestine, heart, and lungs. However, there are still barriers which prevent a lifelong survival of the donor graft in the recipient. Activation of the immune system is an important limiting factor in the transplantation process. As part of this pro-inflammatory environment, the complement system is triggered. Complement activation plays a key role in the transplantation process, as highlighted by the amount of studies in ischemia-reperfusion injury (IRI) and rejection. However, new insight have shown that complement is not only activated in the later stages of transplantation, but already commences in the donor. In deceased donors, complement activation is associated with deteriorated quality of deceased donor organs. Of importance, since most donor organs are derived from either brain-dead donors or deceased after circulatory death donors. The exact mechanisms and the role of the complement system in the pathophysiology of the deceased donor have been underexposed. This review provides an overview of the current knowledge on complement activation in the (multi-)organ donor. Targeting the complement system might be a promising therapeutic strategy to improve the quality of various donor organs. Therefore, we will discuss the complement therapeutics that already have been tested in the donor. Finally, we question whether complement therapeutics should be translated to the clinics and if all organs share the same potential complement targets, considering the physiological differences of each organ. [ABSTRACT FROM AUTHOR]

Introduction: Despite continuous advances in transplant medicine, there is a persistent worldwide shortage of organs available for donation. There is a growing body of research that supports that optimal management of deceased organ donors in Intensive Care Unit can substantially increase the availability of organs for transplant and improve outcomes in transplant recipients. Methods: A systematic literature review was performed, comprising a comprehensive search of the PubMed database for relevant terms, as well as individual assessment of references included in large original investigations, and comprehensive society guidelines. Results: In addition to overall adherence to catastrophic brain injury guidelines, optimization of physiologic state in accordance with established donor management goals (DMGs), and establishment of system-wide processes for ensuring early referral to organ procurement organizations (OPOs), several specific critical care management strategies have been associated with improved rates and outcomes of renal transplantation from deceased donors. These include vasoactive medication selection, maintenance of euvolemia, avoidance of hydroxyethyl starch, glycemic control, targeted temperature management, and blood transfusions if indicated. Conclusions: Management of deceased organ donors should focus first on maintaining adequate perfusion to all organ systems through adherence to standard critical care guidelines, early referral to OPOs, and family support. Furthermore, several specific DMGs and strategies have been recently shown to improve both the rates and outcomes of organ transplantation.