Brain death and postmortem organ donation: Report of a questionnaire from the CENTER-TBI study

Background: We aimed to investigate the extent of the agreement on practices around brain death and postmortem organ donation. Methods: Investigators from 67 Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study centers completed several questionnaires (response rate: 99%). Results: Regarding practices around brain death, we found agreement on the clinical evaluation (prerequisites and neurological assessment) for brain death determination (BDD) in 100% of the centers. However, ancillary tests were required for BDD in 64% of the centers. BDD for nondonor patients was deemed mandatory in 18% of the centers before withdrawing life-sustaining measures (LSM). Also, practices around postmortem organ donation varied. Organ donation after circulatory arrest was forbidden in 45% of the centers. When withdrawal of LSM was contemplated, in 67% of centers the patients with a ventricular drain in situ had this removed, either sometimes or all of the time. Conclusions: This study showed both agreement and some regional differences regarding practices around brain death and postmortem organ donation. We hope our results help quantify and understand potential differences, and provide impetus for current dialogs toward further harmonization of practices around brain death and postmortem organ donation

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury: A survey in 66 neurotrauma centers participating in the CENTER-TBI study

The distributions of species are not only determined by where they can survive – they must also be able to reproduce. Although immigrant inviability is a well-established concept, the fact that immigrants also need to be able to effectively reproduce in foreign environments has not been fully appreciated in the study of adaptive divergence and speciation. Fertilization and reproduction are sensitive life-history stages that could be detrimentally affected for immigrants in non-native habitats. We propose that “immigrant reproductive dysfunction” is a hitherto overlooked aspect of reproductive isolation caused by natural selection on immigrants. This idea is supported by results from experiments on an externally fertilizing fish (sand goby, Pomatoschistus minutus). Growth and condition of adults were not affected by non-native salinity whereas males spawning as immigrants had lower sperm motility and hatching success than residents. We interpret these results as evidence for local adaptation or acclimation of sperm, and possibly also components of paternal care. The resulting loss in fitness, which we call “immigrant reproductive dysfunction,” has the potential to reduce gene flow between populations with locally adapted reproduction, and it may play a role in species distributions and speciation.</p

Variation in structure and process of care in traumatic brain injury: Provider profiles of European Neurotrauma Centers participating in the CENTER-TBI study

Introduction: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Methods: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions.Results: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. Conclusion: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches.</p

Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury: A survey in 66 neurotrauma centers participating in the CENTER-TBI

Background: No definitive evidence exists on how intracranial hypertension should be treated in patients with traumatic brain injury (TBI). It is therefore likely that centers and practitioners individually balance potential benefits and risks of different intracranial pressure (ICP) management strategies, resulting in practice variation. The aim of this study was to examine variation in monitoring and treatment policies for intracranial hypertension in patients with TBI. Methods: A 29-item survey on ICP monitoring and treatment was developed based on literature and expert opinion, and pilot-tested in 16 centers. The questionnaire was sent to 68 neurotrauma centers participating in the Collaborative European Neurotrauma Effectiveness Research (CENTER-TBI) study. Results: The survey was completed by 66 centers (97% response rate). Centers were mainly academic hospitals (n = 60, 91%) and designated level I trauma centers (n = 44, 67%). The Brain Trauma Foundation guidelines were used in 49 (74%) centers. Approximately ninety percent of the participants (n = 58) indicated placing an ICP monitor in patients with severe TBI and computed tomography abnormalities. There was no consensus on other indications or on peri-insertion precautions. We found wide variation in the use of first- and second-tier treatments for elevated ICP. Approximately half of the centers were classified as having a relatively aggressive approach to ICP monitoring and treatment (n = 32, 48%), whereas the others were considered more conservative (n = 34, 52%). Conclusions: Substantial variation was found regarding monitoring and treatment policies in patients with traumatic brain injury and intracranial hypertension. The results of this survey indicate a lack of consensus between European neurotrauma centers and provide an opportunity and necessity for comparative effectiveness research

Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Preventive GC7 reduces brain death-induce renal injuries in a preclinical porcine model

N1-guanyl-1,7-diaminoheptane (GC7), an inhibitor of eIF5A,exhibits anti-inflammatory features and promotes anoxic/ischemic tolerance.Thus, GC7 pretreatment could be useful in order to protect organs submitted toischemia before transplantation in heart-beating donors.Methods: Using a pig brain death donation preclinical model, we carried outthe in vivo evaluation of GC7 pre-treatment (3 mg/kg iv bolus), after braindeath, at the beginning of the 4 h-reanimation, after which one kidney wascollected, cold-stored (18-h in UW), and allo-transplantated in a doublenephrectomizedrecipient. Groups were defined as follows (n = 6 per group):healthy (Control), untreated Brain death (BD) and GC7-treated BD (GC7).Results: R1. At the end of 4 h-reanimation, GC7 decreased (80–100%,p < 0.05) BD-increased markers: (i) eIF5A hypusination, (ii) tissue levels ofreactive oxygen species markers (CellRox staining and Aconitase), (iii) tissuelevels of nitrotyrosine, and (iv) the mitochondrial-dependent apoptosis pathway(Bax/Bcl-2 proapoptotic ratio, Caspase-9). In addition, GC7 increased (2 to 6-fold, p < 0.05) the expression of anti-oxidant proteins (SOD2 and HO-1, as wellas PGC-1a, Nrf2, and total & p-Sirtuin1 & 3). R2. At the end of cold storage,GC7 treatment normalized BD-dependent decrease of SOD2 and HO-1proteins expression (p < 0.05). In addition, GC7 significantly restored the BDdependentincrease of the Bax/Bcl-2 (proapoptotic) ratio (p < 0.05).Conclusion: After the reanimation phase, preventively given GC7 provedprotective for kidneys against brain death-induced injuries; during the coldstorage phase, GC7 appeared to preserve antioxidant defences and to protectmitochondria. Early and long-term, post-transplantation propagation ofobserved protective effects are currently evaluated

Rôle de la modulation mitochondriale au cours de la conservation rénale: évaluation dans un modèle préclinique de donneur décédé par arrêt cardiaque

International audienceObjectifsLa trimétazidine (TMZ), agissant sur le métabolisme de la mitochondrie, a été étudiée dans différentes situations d’ischémie reperfusion avec des effets protecteurs. À partir d’un modèle porcin d’auto-transplantation rénale mimant la situation des donneurs décédés par arrêt cardiaques, l’évaluation de TMZ ajoutée au milieu de conservation a été faite pour étudier l’amélioration de la reprise de fonction et les effets à long terme.MéthodesDes groupes de 7 animaux ont été étudiés: témoin (laparotomie et manipulation douce du pédicule rénale); groupe uninéphrectomisé (ablation du rein gauche); groupe IC60VIA (rein auto-transplanté conservé par Viaspan); groupe IC60VIA + TMZ10 (rein auto-transplanté conservé par Viaspan et 10 mg de TMZ); groupe IC60VIA + 20 (rein auto-transplanté conservé par Viaspan et 20 mg de TMZ). Les reins conservés étaient soumis à 60 minutes d’ischémie chaude par clampage du pédicule rénale suivi par 24 h d’ischémie froide dans la solution Viaspan (UW). La reprise de fonction, le niveau de stress oxydant et la réaction inflammatoire ont été évalués ainsi que les lésions histologiques.RésultatsL’ajout de TMZ améliore significativement (p < 0.05), la reprise de fonction rénale précoce en particulier à la dose de 20 mg par litre de solution, comme en témoigne l’évolution de la créatinine. La fonction tubulaire est également améliorée (p < 0.05) ainsi que le pouvoir de concentration (p < 0.05) durant la phase précoce des 2 semaines post-transplantation. L’analyse histologique à la fin de la première semaine met en évidence une limitation des lésions de nécrose rénale et une amélioration de la réparation. Durant cette première semaine, le niveau plasmatique de 8 iso-prostane, marqueur de la péroxydation lipidique, est également diminué dans les groupes traités et particulièrement avec 20 mg de TMZ. Les cytokines pro-inflammatoires TNF-α et Il-6 sont diminuées dans le plasma durant la première semaine.ConclusionLa TMZ est un agent pharmacologique qui agit sur le métabolisme mitochondriale. Ajouté à une solution de conservation dans un modèle mimant les donneurs décédés après arrêt cardiaque, cet agent pharmacologique limite les effets des principaux mécanismes lésionnels impliqués. Ce type de molécule pourrait être intéressant dans des protocoles de conditonnement comportant des étapes de circulation régionale normothermique (Fig. 1, Fig. 2, Fig. 3)

Objective of 20 hours of liver preservation: development of a porcine experimental model

National audienc

Barriers and Advances in Kidney Preservation

Despite the fact that a significant fraction of kidney graft dysfunctions observed after transplantation is due to ischemia-reperfusion injuries, there is still no clear consensus regarding optimal kidney preservation strategy. This stems directly from the fact that as of yet, the mechanisms underlying ischemia-reperfusion injury are poorly defined, and the role of each preservation parameter is not clearly outlined. In the meantime, as donor demography changes, organ quality is decreasing which directly increases the rate of poor outcome. This situation has an impact on clinical guidelines and impedes their possible harmonization in the transplant community, which has to move towards changing organ preservation paradigms: new concepts must emerge and the definition of a new range of adapted preservation method is of paramount importance. This review presents existing barriers in transplantation (e.g., temperature adjustment and adequate protocol, interest for oxygen addition during preservation, and clear procedure for organ perfusion during machine preservation), discusses the development of novel strategies to overcome them, and exposes the importance of identifying reliable biomarkers to monitor graft quality and predict short and long-term outcomes. Finally, perspectives in therapeutic strategies will also be presented, such as those based on stem cells and their derivatives and innovative models on which they would need to be properly tested