NON-INVASIVE METHODS FOR ASSESSING HEPATIC GRAFT STEATOSIS IN A DECEASED DONOR WHO IS DECLARED BRAIN-DEAD

The increase in the number of patients requiring liver transplantation raises the question of expanding and clarifying the criteria of hepatic grafts suitability for transplantation, and also shows the need to develop new, fast and noninvasive methods for assessing the functional state of the liver at the stage of donor examination and treatment. Hepatic grafts with severe steatosis, previously considered unsuitable for transplantation due to the higher risk of primary graft failure, are now referred to as potential for transplantation. There are several ways to diagnose and determine the stage of steatosis, but, unfortunately, today none of them can give an accurate and rapid assessment of its grade in a hepatic graft. Currently, the "gold standard" for determining liver steatosis is a biopsy with subsequent examination of samples by a pathomorphologist. There are also prognostic models, non-invasive tests and instrumental methods, the effectiveness of which has been proven - these are ultrasound elastography, contrast computed tomography and contrast computed tomography with liver density measurement. The decision on the suitability of a hepatic graft for transplantation depends on many factors, both on the part of the donor and on the part of the recipient, and it would be correct to assume that these data should be taken into account in aggregate. The review covers all the approaches currently used to quantify and qualitatively assess steatosis in liver transplants from a brain-dead donor.

Clinical and subclinical characteristics of brain-dead donors for liver transplantation in Viet Duc University Hospital

Since 2010, 49 cases of liver transplants from brain-dead donors were performed at Viet Duc University Hospital. This study is a descriptive cross-section cohort study with a combined analysis of retrospective and prospective occurrences of a series of cases of liver procurement from brain-dead donors in Viet Duc University Hospital from March 2010 to March 2020. The results of this study showed several features: the average age of the brain-dead donors was 29.8±10.9 (18-69), donors were mostly male (7.17/1, 87.8%), and the main cause of brain death was head trauma. Clinically, 40.8 and 63.3% of the subjects were hypothermic and diagnosed with diabetes insipidus, however, the subjects were all well resuscitated before procurement. Therefore, haemodynamic indices and temperatures were maintained at stable levels and there was no statistically significant difference. In subclinical aspects, haemoglobin and platelet levels decreased significantly but remained within the target criteria during resuscitation while blood sodium levels increased significantly during resuscitation when compared with levels at the time of admission (p<0.001) thus corresponding to diabetes insipidus. In general, 44.90% of donors were within the ideal standard, and in the extended standard group, the highest rate was electrolyte disorders (32.65%). In conclusion, there are many variations in clinical and paraclinical body signs as well as homeostasis in the brain-dead donors. Of these signs, the most prominent were changes in haemodynamics, temperature, urine output, complete blood count, blood clotting, and blood sodium levels. These are all factors that are included in the criteria to consider the selection of a liver donor.

A translational rat model for ex vivo lung perfusion of pre-injured lungs after brain death

The process of brain death (BD) detrimentally affects donor lung quality. Ex vivo lung perfusion (EVLP) is a technique originally designed to evaluate marginal donor lungs. Nowadays, its potential as a treatment platform to repair damaged donor lungs is increasingly studied in experimental models. Rat models for EVLP have been described in literature before, yet the pathophysiology of BD was not included in these protocols and prolonged perfusion over 3 hours without anti-inflammatory additives was not achieved. We aimed to establish a model for prolonged EVLP of rat lungs from brain-dead donors, to provide a reliable platform for future experimental studies. Rat lungs were randomly assigned to one of four experimental groups (n = 7/group): 1) healthy, directly procured lungs, 2) lungs procured from rats subjected to 3 hours of BD and 1 hour cold storage (CS), 3) healthy, directly procured lungs subjected to 6 hours EVLP and 4), lungs procured from rats subjected to 3 hours of BD, 1 hour CS and 6 hours EVLP. Lungs from brain-dead rats showed deteriorated ventilation parameters and augmented lung damage when compared to healthy controls, in accordance with the pathophysiology of BD. Subsequent ex vivo perfusion for 6 hours was achieved, both for lungs of healthy donor rats as for pre-injured donor lungs from brain-dead rats. The worsened quality of lungs from brain-dead donors was evident during EVLP as well, as corroborated by deteriorated ventilation performance, increased lactate production and augmented inflammatory status during EVLP. In conclusion, we established a stable model for prolonged EVLP of pre-injured lungs from brain-dead donor rats. In this report we describe tips and pitfalls in the establishment of the rat EVLP model, to enhance reproducibility by other researchers.

Prevalence of Coronavirus Disease 2019 in the Brain-Dead Candidates for Transplantation and Uncommon Manifestations of the Infection

Aim: This study aimed to evaluate the prevalence of Coronavirus Disease 2019 (COVID-19) positive cases meeting clinical brain death criteria; moreover, it was attempted to assess the uncommon manifestations of the infection in this study. Materials and Methods: This retrospective observational study was conducted on all brain-dead patients who were referred to the emergency department of hospitals in Mashhad, Iran, from February to October 2020. The demographic characteristics, clinical information, and laboratory data were collected and recorded in a researcher-made checklist. Results: In general, 70 patients were included in this study. The PCR test result was positive for COVID-19 in 54% of the patients, and syncope was reported in 16.1% of the cases (n=10). Furthermore, the majority of the patients (52.9%) showed central nervous system (CNS) hemorrhagic manifestations. A comparison was made between the patients with positive and negative PCR test result in terms of syncope; accordingly, there was a significant difference between them in this regard (χ2=4.5; P=0.03). The CNS hemorrhagic manifestations were significantly higher in patients with positive PCR compared to those with negative PCR (χ2=4.57, P=0.03). Moreover, the grand glass opacity and pleural effusion were the most common findings of the chest computed tomography in brain-dead patients with COVID-19. Conclusion: Due to the high prevalence of COVID-19 among brain-dead patients, it seems that syncope attack should be regarded as one of the possible symptoms of COVID-19. Moreover, syncope as a result of COVID-19 may itself cause traumatic events. It is worth mentioning that CNS hemorrhagic manifestations have been reported in more than half of the patients with brain death.

A multicenter randomized placebo-controlled trial of intravenous thyroxine for heart-eligible brain-dead organ donors

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.govNCT04415658. Registered on June 4, 2020

Case Report: Fatal Neurotoxicity Following Resmethrin Poisoning in a Child

Resmethrin, a type I pyrethroid insecticide, can activate sodium channels, causing neurotoxicity in both mammals and insects. Possible routes of poisoning include inhalation, dermal contact and ingestion. There are no specific symptoms for resmethrin poisoning. Until now, no antidote has been available for resmethrin. Resmethrin poisoning is rarely reported in children. Here, we report a fatal case of resmethrin poisoning that might have been caused by accidental ingestion by a 26-month-old child. He presented with neurotoxic symptoms that included vomiting, recurrent seizures, and coma. The cranial CT showed extensive lesions of low intensity in the bilateral white matter, thalamus, brainstem, and cerebellum. Lumbar punctures showed increased intracranial pressure (ICP &gt; 25 mmHg). Cerebrospinal fluid (CSF) tests revealed that protein was elevated to 289.2 mg/dL without pleocytosis. Resmethrin was detected in his blood by liquid chromatography-mass spectrometry, which confirmed the diagnosis of resmethrin poisoning. The child developed brain stem herniation and then was declared brain dead at the 77th h after admission. Resmethrin poisoning can be fatal, and it requires immediate diagnosis and treatment. Previous studies reported that cranial CT and CSF analyses were all normal in patients with pyrethroid poisoning. This case might extend the knowledge of neuroimaging and CSF analysis in children with resmethrin poisoning.