Plasma proteome of brain-dead organ donors predicts heart transplant outcome.

BACKGROUND: The pathophysiological changes related to brain death may affect the quality of the transplanted organs and expose the recipients to risks. We probed systemic changes reflected in donor plasma proteome and investigated their relationship to heart transplant outcomes. METHODS: Plasma samples from brain-dead multi-organ donors were analyzed by label-free protein quantification using high-definition mass spectrometry. Unsupervised and supervised statistical models were used to determine proteome differences between brain-dead donors and healthy controls. Proteome variation and the corresponding biological pathways were analyzed and correlated with transplant outcomes. RESULTS: Statistical models revealed that donors had a unique but heterogeneous plasma proteome with 237 of 463 proteins being changed compared to controls. Pathway analysis showed that coagulation, gluconeogenesis, and glycolysis pathways were upregulated in donors, while complement, LXR/RXR activation, and production of nitric oxide and reactive oxygen species in macrophages pathways were downregulated. In point-biserial correlation analysis, lysine-specific demethylase 3A was moderately correlated with any grade and severe PGD. In univariate and multivariate Cox regression analyses myosin Va and proteasome activator complex subunit 2 were significantly associated with the development of acute rejections with hemodynamic compromise within 30 days. Finally, we found that elevated levels of lysine-specific demethylase 3A and moesin were identified as predictors for graft-related 1-year mortality in univariate analysis. CONCLUSIONS: We show that brain death significantly changed plasma proteome signature Donor plasma protein changes related to endothelial cell and cardiomyocyte function, inflammation, and vascular growth and arteriogenesis could predict transplant outcome suggesting a role in donor evaluation.

Brain-dead and coma patients exhibit different serum metabolic profiles: preliminary investigation of a novel diagnostic approach in neurocritical care.

There is a clear difference between severe brain damage and brain death. However, in clinical practice, the differentiation of these states can be challenging. Currently, there are no laboratory tools that facilitate brain death diagnosis. The aim of our study was to evaluate the utility of serum metabolomic analysis in differentiating coma patients (CP) from individuals with brain death (BD). Serum samples were collected from 23 adult individuals with established diagnosis of brain death and 24 patients in coma with Glasgow Coma Scale 3 or 4, with no other clinical symptoms of brain death for at least 7 days after sample collection. Serum metabolomic profiles were investigated using proton nuclear magnetic resonance (NMR) spectroscopy. The results obtained were examined by univariate and multivariate data analysis (PCA, PLS-DA, and OPLS-DA). Metabolic profiling allowed us to quantify 43 resonance signals, of which 34 were identified. Multivariate statistical modeling revealed a highly significant separation between coma patients and brain-dead individuals, as well as strong predictive potential. The findings not only highlight the potential of the metabolomic approach for distinguishing patients in coma from those in the state of brain death but also may provide an understanding of the pathogenic mechanisms underlying these conditions.

Metabolic values precluding clinical death by neurologic Criteria/Brain death: Survey of neurocritical care society physicians.

BACKGROUND: There are no established ranges for metabolic values prior to death by neurologic criteria/brain death determination (DNC/BD) and the thresholds required by institutional protocols and accepted by neurointensivists is unknown. METHODS: We designed a survey that addressed 1) the metabolic tests required in institutional guidelines prior to brain death determination, 2) the metabolic tests the respondent reviewed prior to brain death determination, and 3) the metabolic test thresholds for laboratory tests that were perceived to preclude or permit clinical DNC/BD determination. The survey was distributed online to physicians in the Neurocritical Care Society from September to December 2019. Respondents were dichotomized based on the number of brain death evaluations they had performed (≤20 vs. > 20) and responses were compared between groups. RESULTS: The survey was completed by 84 physicians. Nearly half (47.6%) of respondents did not believe their institutions required metabolic testing. The metabolic testing for which institutions most commonly provided a defined threshold were arterial pH (34.5%, 29/84), sodium (28.6%, 24/84), and glucose (15.5%, 13/84). Nearly all (97.6%) respondents routinely reviewed metabolic tests prior to brain death evaluation, the most common of which were: sodium (91.7%, 77/84), arterial pH (83.3%, 70/84), and glucose (79.8%, 67/84). Respondents who had performed > 20 evaluations were less likely to check thyroxine and total bilirubin (3.6%, 2/55 vs. 20.7%, 6/29 (p = 0.011) and 12.7%, 7/55 vs. 31%, 9/29 (p = 0.042), respectively), and had a more liberal upper limit of potassium (6.3 mEq/L vs 6.0 mEq/L, p = 0.045). CONCLUSION: Prior to brain death evaluation, neurocritical care providers commonly review similar metabolic tests and have similar thresholds regarding values that would preclude clinical brain death determination. This finding is independent of experience with brain death determination.

Prognostic value of serum pentraxin 3 for intracerebral hemorrhage mortality.

Pentraxin 3 is considered an important inflammatory marker is known to increase in patients with ischemic stroke, but the relationship between pentraxin 3 and intracerebral hemorrhage mortality is unclear. The purpose of this study is to investigate the level of pentraxin 3 in serum and its impact on prognosis in 307 patients with intracerebral hemorrhage. During the 5-year follow-up, the mortality rate of patients with intracerebral hemorrhage was 22.5%. The serum pentraxin 3 level of the brain-dead patients was higher than that of the control group (P < 0.05). Logistic regression analysis indicated a high correlation between the pentraxin 3 level and the mortality rate 95% (hazard ratio: 3.671; confidence interval: 1.558-4.297). The receiver operating characteristic curve showed that pentraxin 3 (Area Under Curve = 0.801) had a higher diagnostic value than C-reactive protein (Area Under Curve = 0.701). The pentraxin 3 level increased significantly after intracerebral hemorrhage and has an important predictive value for a prognosis for intracerebral hemorrhage mortality.

Circulating CXCL10 and IL-6 in solid organ donors after brain death predict graft outcomes.

We tested the hypothesis that circulating CXCL10 and IL-6 in donor after brain death provide independent additional predictors of graft outcome. From January 1, 2010 to June 30, 2012 all donors after brain death managed by the NITp (n = 1100) were prospectively included in this study. CXCL10 and IL-6 were measured on serum collected for the crossmatch at the beginning of the observation period. Graft outcome in recipients who received kidney (n = 1325, follow-up 4.9 years), liver (n = 815, follow-up 4.3 years) and heart (n = 272, follow-up 5 years) was evaluated. Both CXCL-10 and IL-6 showed increased concentration in donors after brain death. The intensive care unit stay, the hemodynamic instability, the cause of death, the presence of risk factors for cardiovascular disease and the presence of ongoing infection resulted as significant determinants of IL-6 and CXCL10 donor concentrations. Both cytokines resulted as independent predictors of Immediate Graft Function. Donor IL-6 or CXCL10 were associated with graft failure after liver transplant, and acted as predictors of recipient survival after kidney, liver and heart transplantation. Serum donor IL-6 and CXCL10 concentration can provide independent incremental prediction of graft outcome among recipients followed according to standard clinical practice.

Effects of mild hypothermia on serum HMGB1 of brain-dead donors and its impact on kidney transplantation recipients.

Investigate the effect of mild hypothermia on serum inflammatory factor HMGB1 of brain-dead donors, and its significance for renal transplantation recipients.In our hospital between January 2018 and January 2019 up to the standard of brain death donor (aged 18 to 65 years old) prospective cohort study, brain death donor were randomly divided into mild hypothermia group and the non-mild hypothermia group. Serum were collected from donor at different periods, and enzyme-linked immunoassay (ELISA) was used to determine the serum HMGB1 concentration to compare the difference between the 2 donor groups. The early recovery of renal function after renal transplantation was followed up, and the incidence of delayed graft function (DGF) and early recovery of renal function were compared between the 2 groups. The correlation between donor HMGB1 and recipient DGF was analyzed.Between 17 donors in the mild hypothermia group and 17 in the non-mild hypothermia group, there were no statistically significant differences in the age, perioperative urine volume and ICU stay between the 2 groups. After mild hypothermia treatment, serum HMGB1 levels of brain death donors were significantly decreased. While in non-mild hypothermia brain death donor group without treatment, serum HMGB1 was significantly increased. There were no statistically significant differences in age and preoperative creatinine between the 2 recipient groups, including 33 patients in the mild hypothermia group and 34 patients in the non-mild hypothermia group. DGF incidence was lower in mild hypothermia group comparing with non-mild hypothermia group with statistical significance. The levels of HMGB1 from donor before procurement is correlated with the occurrence of DGF of the recipient.Mild hypothermia therapy can reduce the levels of serum HMGB1, improve the function of donor organs. The levels of HMGB1 before donor procurement can be used to predict the occurrence of DGF in kidney transplant recipients. Our study shows that HMGB1 can be potentially used as therapeutic target of early intervention for brain death donors. Furthermore, mild hypothermia therapy can be applied in the maintenance of brain death donors for kidney transplant recipient to improve the successful rate of transplantation.

Brain Death Induction in Mice Using Intra-Arterial Blood Pressure Monitoring and Ventilation via Tracheostomy.

While both living donation and donation after circulatory death provide alternative opportunities for organ transplantation, donation after donor brain death (BD) still represents the major source for solid transplants. Unfortunately, the irreversible loss of brain function is known to induce multiple pathophysiological changes, including hemodynamic as well as hormonal modifications, finally leading to a systemic inflammatory response. Models that allow a systematic investigation of these effects in vivo are scarce. We present a murine model of BD induction, which could aid investigations into the devastating effects of BD on allograft quality. After implementing intra-arterial blood pressure measurement via the common carotid artery and reliable ventilation via a tracheostomy, BD is induced by steadily increasing intracranial pressure using a balloon catheter. Four hours after BD induction, organs may be harvested for analysis or for further transplantation procedures. Our strategy enables the comprehensive analysis of donor BD in a murine model, therefore allowing an in-depth understanding of BD-related effects in solid organ transplantation and potentially paving the way to optimized organ preconditioning.

Red Cell Distribution Width in Diagnosis of Brain Death.

INTRODUCTION: Red blood cell distribution (RDW) is a hematologic index automatically calculated by blood cell counters. Research about RDW in traumatic brain injury showed positive correlation between high RDW values and mortality, which inspired us to investigate whether RDW could be used as a supportive diagnostic biomarker for diagnosis of brain death. Our hypothesis is that RDW may be useful as a biomarker that supports the diagnosis of brain death. METHODS: After approval of the ethics committee, 209 patients who had been diagnosed with brain death between January 2012 and July 2018 were retrospectively reviewed. The RDW values of patients on the days of admission, brain death, and cardiac arrest were recorded. Data were collected from hospital database and patient charts. RESULTS: Statistical analysis revealed that the RDW values on the days of brain death and cardiac arrest were significantly higher than on the day of admission. In addition, the RDW values for the cardiac arrest day were significantly higher than on the day of brain death (P < .001). CONCLUSIONS: We can say that the increase in RDW, which is reported to be an indicator of mortality for many diseases, can be a supporting biomarker for brain death diagnosis when evaluated concomitantly with clinical diagnostic criteria.

Biomarkers and Donor Selection in Heart Transplantation.

BACKGROUND: Previously, we showed that B-type natriuretic peptide (BNP) measured in the donor was related to cardiac performance after cardiac transplantation. The present study assesses the value of 3 biomarkers in the selection of donor hearts in a larger cohort. METHODS: Blood samples were prospectively obtained in 105 brain-dead patients scheduled for heart donation. BNP, soluble suppressor of tumorigenicity 2 (ST2), and troponin of heart donors were correlated with hemodynamic parameters early after transplantation as well as with the mortality of the recipients. RESULTS: A significant inverse relationship was found between donor BNP measured at the time of donation and recipient cardiac index and cardiac output at day 13 post-transplantation (r = -0.31, P = .005, and r = -0.34, P = .0016, respectively). Logistic regression analysis-including BNP, ST2, and troponin-showed that donor BNP was a predictor of a poor cardiac index (< 2.2 L/min/m2) in the recipient (P = .04). A donor BNP > 132 pg/mL has a sensitivity of 56% (95% confidence interval 21-86) and a specificity of 86% (95% confidence interval 77-93) to predict poor cardiac performance in the recipient. When the donor BNP is ≤ 132 pg/mL, the risk of a poor cardiac function in the recipient is very low (negative predictive value 94%). Mortality at 30 days was also correlated to donor BNP (r = 0.29, P = .0029). Long-term survival of the recipient was not correlated to the biomarkers measured in the donor. CONCLUSION: Donor BNP, but not donor ST2 or high-sensitivity troponin, provides information on the donor heart and early post-transplant performance, including 1-month mortality.

EGF-GH Axis in Rat Steatotic and Non-steatotic Liver Transplantation From Brain-dead Donors.

BACKGROUND: We evaluated the potential dysfunction caused by changes in growth hormone (GH) levels after brain death (BD), and the effects of modulating GH through exogenous epidermal growth factor (EGF) in steatotic and nonsteatotic grafts. METHODS: Steatotic and nonsteatotic grafts from non-BD and BD rat donors were cold stored for 6 hours and transplanted to live rats. Administration of GH and EGF and their underlying mechanisms were characterized in recipients of steatotic and nonsteatotic grafts from BD donors maintained normotensive during the 6 hours before donation. Circulating and hepatic GH and EGF levels, hepatic damage, and regeneration parameters were evaluated. Recipient survival was monitored for 14 days. Somatostatin, ghrelin, and GH-releasing hormones that regulate GH secretion from the anterior pituitary were determined. The survival signaling pathway phosphoinositide-3-kinase/protein kinase B that regulates inflammation (suppressors of cytokine signaling, high-mobility group protein B1, oxidative stress, and neutrophil accumulation) was evaluated. RESULTS: BD reduced circulating GH and increased GH levels only in steatotic livers. GH administration exacerbated adverse BD-associated effects in both types of graft. Exogenous EGF reduced GH in steatotic livers, thus activating cell proliferation and survival signaling pathways, ultimately reducing injury and inflammation. However, EGF increased GH in nonsteatotic grafts, which exacerbated damage. The benefits of EGF for steatotic grafts were associated with increased levels of somatostatin, a GH inhibitor, whereas the deleterious effect on nonsteatotic grafts was exerted through increased amounts of ghrelin, a GH stimulator. CONCLUSIONS: GH treatment is not appropriate in rat liver transplant from BD donors, whereas EGF (throughout GH inhibition) protects only in steatotic grafts.

Brain death-induced cytokine release is not associated with primary graft dysfunction: a cohort study. / A liberação de citocinas induzida pela morte cerebral não está associada à disfunção primária do enxerto: um estudo de coorte.

OBJECTIVE: To examine the association between donor plasma cytokine levels and the development of primary graft dysfunction of organs transplanted from deceased donors. METHODS: Seventeen deceased donors and the respective 47 transplant recipients were prospectively included in the study. Recipients were divided into two groups: group 1, patients who developed primary graft dysfunction; and group 2, patients who did not develop primary graft dysfunction. Donor plasma levels of TNF, IL-6, IL-1ß, and IFN-γ assessed by ELISA were compared between groups. RESULTS: Sixty-nine organs were retrieved, and 48 transplants were performed. Donor plasma cytokine levels did not differ between groups (in pg/mL): TNF, group 1: 10.8 (4.3 - 30.8) versus group 2: 8.7 (4.1 - 33.1), p = 0.63; IL-6, group 1: 1617.8 (106.7 - 5361.7) versus group 2: 922.9 (161.7 - 5361.7), p = 0.56; IL-1ß, group 1: 0.1 (0.1 - 126.1) versus group 2: 0.1 (0.1 - 243.6), p = 0.60; and IFN-γ, group 1: 0.03 (0.02 - 0.2) versus group 2: 0.03 (0.02 - 0.1), p = 0.93). Similar findings were obtained when kidney transplants were analyzed separately. CONCLUSION: In this sample of transplant recipients, deceased donor plasma cytokines TNF, IL-6, IL-1ß, and IFN-γ were not associated with the development of primary graft dysfunction.

OBJETIVO: Examinar a associação entre os níveis de citocinas no plasma do doador e o desenvolvimento de disfunção primária do enxerto de órgãos transplantados a partir de doadores falecidos. MÉTODOS: Foram incluídos no estudo de forma prospectiva 17 doadores falecidos e os respectivos 47 pacientes receptores de transplante. Os receptores foram divididos em dois grupos: grupo 1, de pacientes que desenvolveram disfunção primária do enxerto, e grupo 2, de pacientes que não desenvolveram disfunção primária do enxerto. Os níveis de TNF, IL-6, IL-1ß, e IFN-γ, avaliados por meio de ELISA, foram comparados entre os grupos. RESULTADOS: Obtiveram-se 69 órgãos, sendo realizados 48 transplantes. Os níveis plasmáticos de citocinas nos doadores não diferiram entre os grupos (em pg/mL): TNF no grupo 1, com 10,8 (4,3 - 30,8) versus no grupo 2, com 8,7 (4,1 - 33,1), com valor de p = 0,63; IL-6 no grupo 1: 1.617,8 (106,7 - 5.361,7) versus no grupo 2: 922,9 (161,7 - 5.361,7), com p = 0,56; IL-1ß, no grupo 1: 0,1 (0,1 - 126,1) versus no grupo 2: 0,1 (0,1 - 243,6), com p = 0,60; e IFN-γ, no grupo 1: 0,03 (0,02 - 0,2) versus no grupo 2: 0,03 (0,02 - 0,1), p = 0,93). Obtivemos resultados similares ao examinar separadamente os casos de transplante renal. CONCLUSÃO: Nesta amostra de receptores de transplante, os níveis plasmáticos das citocinas TNF, IL-6, IL-1ß e IFN-γ nos doadores não se associaram com o desenvolvimento de disfunção primária do enxerto.

A liberação de citocinas induzida pela morte cerebral não está associada à disfunção primária do enxerto: um estudo de coorte / Brain death-induced cytokine release is not associated with primary graft dysfunction: a cohort study

RESUMO Objetivo: Examinar a associação entre os níveis de citocinas no plasma do doador e o desenvolvimento de disfunção primária do enxerto de órgãos transplantados a partir de doadores falecidos. Métodos: Foram incluídos no estudo de forma prospectiva 17 doadores falecidos e os respectivos 47 pacientes receptores de transplante. Os receptores foram divididos em dois grupos: grupo 1, de pacientes que desenvolveram disfunção primária do enxerto, e grupo 2, de pacientes que não desenvolveram disfunção primária do enxerto. Os níveis de TNF, IL-6, IL-1β, e IFN-γ, avaliados por meio de ELISA, foram comparados entre os grupos. Resultados: Obtiveram-se 69 órgãos, sendo realizados 48 transplantes. Os níveis plasmáticos de citocinas nos doadores não diferiram entre os grupos (em pg/mL): TNF no grupo 1, com 10,8 (4,3 - 30,8) versus no grupo 2, com 8,7 (4,1 - 33,1), com valor de p = 0,63; IL-6 no grupo 1: 1.617,8 (106,7 - 5.361,7) versus no grupo 2: 922,9 (161,7 - 5.361,7), com p = 0,56; IL-1β, no grupo 1: 0,1 (0,1 - 126,1) versus no grupo 2: 0,1 (0,1 - 243,6), com p = 0,60; e IFN-γ, no grupo 1: 0,03 (0,02 - 0,2) versus no grupo 2: 0,03 (0,02 - 0,1), p = 0,93). Obtivemos resultados similares ao examinar separadamente os casos de transplante renal. Conclusão: Nesta amostra de receptores de transplante, os níveis plasmáticos das citocinas TNF, IL-6, IL-1β e IFN-γ nos doadores não se associaram com o desenvolvimento de disfunção primária do enxerto.

ABSTRACT Objective: To examine the association between donor plasma cytokine levels and the development of primary graft dysfunction of organs transplanted from deceased donors. Methods: Seventeen deceased donors and the respective 47 transplant recipients were prospectively included in the study. Recipients were divided into two groups: group 1, patients who developed primary graft dysfunction; and group 2, patients who did not develop primary graft dysfunction. Donor plasma levels of TNF, IL-6, IL-1β, and IFN-γ assessed by ELISA were compared between groups. Results: Sixty-nine organs were retrieved, and 48 transplants were performed. Donor plasma cytokine levels did not differ between groups (in pg/mL): TNF, group 1: 10.8 (4.3 - 30.8) versus group 2: 8.7 (4.1 - 33.1), p = 0.63; IL-6, group 1: 1617.8 (106.7 - 5361.7) versus group 2: 922.9 (161.7 - 5361.7), p = 0.56; IL-1β, group 1: 0.1 (0.1 - 126.1) versus group 2: 0.1 (0.1 - 243.6), p = 0.60; and IFN-γ, group 1: 0.03 (0.02 - 0.2) versus group 2: 0.03 (0.02 - 0.1), p = 0.93). Similar findings were obtained when kidney transplants were analyzed separately. Conclusion: In this sample of transplant recipients, deceased donor plasma cytokines TNF, IL-6, IL-1β, and IFN-γ were not associated with the development of primary graft dysfunction.

Use of Venous Pco2 in Determination of Death by Neurological Criteria in Children.

BACKGROUND: Compare the increase in partial pressure of carbon dioxide (Pco2) from venous blood samples with that of arterial blood samples during apnea challenge test in determination of death by neurological criteria. METHODS: Prospective nonrandomized cohort study in tertiary care pediatric intensive care unit. Patients older than 37 week's gestation admitted to PICU with irreversible brain injury at the time when attending physician will perform apnea challenge test as part of brain death examination from October 2015 till September 2017. INTERVENTIONS: None. RESULTS: The primary outcome was to measure and compare the increase in Pco2 from venous blood samples with that from arterial blood samples during apnea challenge test. A total of nine apnea challenge tests from seven patients (ages five months to 17 years) were included in the study. Pco2 in venous blood sample increased less than that in arterial blood samples (venous, 26.1 mm Hg; S.D., 10.1; 95% confidence interval, 18 to 34 mm Hg; arterial, 33.9 mm Hg; S.D., 12.0; 95% confidence interval, 24 to 43 mm Hg) (P = 0.02). CONCLUSION: Postapnea challenge test Pco2 of 60 mm Hg along with increase of 20 mm Hg in venous blood sample correlated to Pco2 greater than 60 mm Hg along with increase of greater than 20 mm Hg in arterial blood sample. Further studies are warranted to assess if current recommendations for determination of death by neurological criteria in children can be modified to allow for use of venous blood samples as an alternate to arterial blood samples.

Bedside contrast-enhanced ultrasound diagnosing cessation of cerebral circulation in a neonate: A novel bedside diagnostic tool.

Imaging diagnosis of brain death is performed with either four-vessel cerebral angiography or radionuclide cerebral blood flow studies. Unfortunately, timely performance of either study at a critically ill period is not only cumbersome but not feasible in many cases. We present a case of a 6-month-old male three hours status post-cardiac arrest of unknown etiology who underwent contrast-enhanced ultrasound (CEUS) for diagnosis of near absent perfusion, or near brain death. The patient passed away 30 minutes after the exam and clinical diagnosis of brain death was confirmed. The case report highlights the utility of CEUS for diagnosis of brain death. This can have significant clinical implications in neonates who may not be eligible for commonly used, cumbersome radiologic studies for diagnosis of brain death.

Brain Death-Induced Inflammatory Activity is Similar to Sepsis-Induced Cytokine Release.

Brain death (BD) is associated with a systemic inflammation leading to worse graft outcomes. This study aimed to compare plasma cytokine values between brain-dead and critically ill patients, including septic and non-septic controls, and evaluate cytokine release kinetics in BD. Sixteen brain-dead and 32 control patients (16 with and 16 without sepsis) were included. Plasma cytokines were measured by magnetic bead assay after the first clinical exam consistent with BD and every 6 hours thereafter, and at the time of study entry in the control group. The values for IL-8 and IFN-γ were higher in brain-dead and septic patients than in non-septic patients [IL-8: 80.3 (18.7-169.6) vs. 68.2 (22.4-359.4) vs. 16.4 (9.2-42.7) pg/mL; P = 0.006; IFN-γ: 2.8 (1.6-6.1) vs. 3.4 (1.2-9.0) vs. 0.5 (0.5-1.8) pg/mL; P = 0.012]. TNF showed a clear tendency to increase in brain-dead patients [2.7 (1.0-4.8) vs. 1.0 (1.0-5.6) vs. 1.0 (1.0-1.0) pg/mL; P = 0.051], and IL-6 values were higher in brain-dead patients than in non-septic controls [174.5 (104.9-692.5) vs. 13.2 (7.3-38.6) pg/mL; P = 0.002]. These differences remained even after excluding brain-dead patients who also had sepsis ( n = 3). IL-1ß and IL-10 values increased from baseline to time point 2 (∼6 hours later) [IL-1ß: 5.39 (1.93-16.89) vs. 7.11 (1.93-29.13) pg/mL; P = 0.012; IL-10: 8.78 (3.62-16.49) vs. 15.73 (5.49-23.98) pg/mL; P = 0.009]. BD-induced and sepsis-induced plasma cytokine values were similarly high, and both were higher than the observed in non-septic critically ill patients.

Alterations in thyroid hormones in brain-dead patients are related to non-thyroidal illness syndrome.

INTRODUCTION: Alterations in thyroid hormone levels occur in patients with acute neurological disease states. The aim of this study is to study changes in thyroid hormones in patients with brain death (BD). MATERIAL AND METHODS: Eleven brain-dead patients were studied prospectively. Thyroid hormones were measured on admission to the intensive care unit, the day before BD diagnosis (BD before), and the day after BD diagnosis (BD day). RESULTS: Thyroid stimulating hormone (TSH) and free triiodothyronine (fT3) concentrations were found to be significantly low on ad-mission, BD before, and BD day compared to age-matched healthy controls. TSH levels were shown to be increasing on BD day. Free thyroxine (fT4) levels were within normal limits in all cases except in one case having low fT4 levels with normal TSH levels. No statisti-cally significant changes were encountered between admission thyroid hormone levels and BD-before and BD-day thyroid hormone levels. Six patients were on steroid therapy when BD-before blood samples were drawn, and no difference in thyroid hormone levels was encountered between steroid users and non-users. Correlation analysis showed a positive correlation between GCS and TSH, but a negative association between fT3 and APACHE II. CONCLUSION: We have shown that patients with BD have altered thyroid hormones days before BD diagnosis, and these alterations con-tinue until the diagnosis of BD. The changes in thyroid hormones are compatible with non-thyroidal illness syndrome.

Predictors of Organ Donation Among Patients With Brain Death in the Intensive Care Unit.

INTRODUCTION: Despite the improved care of potential organ donors with probable brain death (BD) in the intensive care unit (ICU), few epidemiologic and clinical data are available in developing countries. OBJECTIVES: To evaluate ICU patients with suspected BD aiming to identify factors possibly related to success (organ donation) or failure (nondonation). METHODS: Retrospective cohort study, from the patient records of an adult ICU of a Brazilian teaching hospital for 12 months. Data were tabulated, and descriptive statistics and univariate and multivariate analyses were performed. RESULTS: During the study period, 85 patients with acute neurologic diseases and suspected BD were admitted to the ICU and included for analysis. Of these, there were 9 organ donors (7 liver and 9 kidney donors); 77.7% were men, with a mean age of 39.6 years and admission Acute Physiology and Chronic Health Evaluation II of 25.5. Two-thirds of the patients were victims of trauma. The mean time between acute neurologic event and organ withdrawal was 269 hours. The main prognostic factors related to the success of organ donation were the maximum serum lactate and creatinine levels during ICU admission. CONCLUSIONS: The main clinical factors correlated with nonevolution for organ donation among ICU patients with clinical suspicion of BD were related to patient severity and organic dysfunction: serum lactate and creatinine level. Clinical care and monitoring are emphasized to improve the efficiency of the donation process.

Clinical Implication of Tests for Prostate-specific Antigen in Brain-dead Organ Donors.

BACKGROUND: Although cancer screening tests are not mentioned under brain-dead organ donor care guidelines in Korea, we assessed the level of prostate-specific antigen (PSA), an important prostate cancer marker, and performed prostate biopsies when needed in brain-dead organ donors. We believe that insisting on a screening test for cancer diagnosis in donors' organs is important. MATERIALS AND METHODS: Data were collected between January 2010 and July 2015 from Ajou University Hospital. We retrospectively analyzed the PSA levels and prostate biopsy results in 111 male brain-dead organ donors (mean age, 48.4 years). RESULTS: The mean PSA level was 7.395 ng/mL (range, 0.062 to 61.780; reference, 0 to 4 ng/mL). Ultrasonography or computed tomographic examination did not reveal prostate cancer, and a rectal examination was not performed. After checking the PSA levels, prostate biopsies were performed in 16 patients based on the recommendations of a urologist, and 4 patients (3.6% of 111) were diagnosed with prostate cancer. All cancers involved adenocarcinomas (acinar type) histopathologically. In 2 patients, the Gleason score was 6 (3 + 3), whereas the other 2 showed a score of 7 (3 + 4). Among the patients diagnosed with prostate cancer, 1 donated his liver and corneas, and the remaining 3 could not donate. CONCLUSION: Well-defined cancer screening tests are needed in Korea. Additionally, when the probability of organ transplantation-induced cancer metastasis is low or a recipient is at a high risk owing to not receiving organs, the law should allow organ donation even if prostate cancer is diagnosed in the donor.