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Introduction: Brain death (BD) is known to compromise graft quality by causing hemodynamic, metabolic, and hormonal changes. The abrupt reduction of female sex hormones after BD was associated with increased lung inflammation. The use of both corticoids and estradiol independently has presented positive results in modulating BD-induced inflammatory response. However, studies have shown that for females the presence of both estrogen and corticoids is necessary to ensure adequate immune response. In that sense, this study aims to investigate how the association of methylprednisolone (MP) and estradiol (E2) could modulate the lung inflammation triggered by BD in female rats. Methods: Female Wistar rats (8 weeks) were divided into four groups: sham (animals submitted to the surgical process, without induction of BD), BD (animals submitted to BD), MP/E2 (animals submitted to BD that received MP and E2 treatment 3h after BD induction) and MP (animals submitted to BD that received MP treatment 3h after BD induction). Results: Hemodynamics, systemic and local quantification of IL-6, IL-1ß, VEGF, and TNF-α, leukocyte infiltration to the lung parenchyma and airways, and adhesion molecule expression were analyzed. After treatment, MP/E2 association was able to reinstate mean arterial pressure to levels close to Sham animals (p<0.05). BD increased leukocyte infiltration to the airways and MP/E2 was able to reduce the number of cells (p=0.0139). Also, the associated treatment modulated the vasculature by reducing the expression of VEGF (p=0.0616) and maintaining eNOS levels (p=0.004) in lung tissue. Discussion: Data presented in this study show that the association between corticoids and estradiol could represent a better treatment strategy for lung inflammation in the female BD donor by presenting a positive effect in the hemodynamic management of the donor, as well as by reducing infiltrated leukocyte to the airways and release of inflammatory markers in the short and long term.

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Lung transplantation stands as a vital treatment for severe lung diseases, primarily sourcing organs from donors with brain death (BD). This research delved into the potential anti-inflammatory effects of thalidomide in rats with BD-induced lung complications. In this study twenty-four Wistar rats were divided into three groups: the control (CTR), brain death (BD) and brain death + thalidomide (TLD) groups. Post specific procedures, a 360 min monitoring period ensued. Comprehensive analyses of blood and heart-lung samples were conducted. Elevated IL-6 levels characterized both BD and TLD groups relative to the CTR (p = 0.0067 and p = 0.0137). Furthermore, TNF-α levels were notably higher in the BD group than both CTR and TLD (p = 0.0152 and p = 0.0495). Additionally, IL-1ß concentrations were significantly pronounced in both BD and TLD compared to CTR, with the BD group surpassing TLD (p = 0.0256). Immunohistochemical assessments revealed augmented NF-ĸB expression in the BD group in comparison to both CTR and TLD (p = 0.0006 and p = 0.0005). With this study we can conclude that BD induced acute pulmonary inflammation, whereas thalidomide manifested a notable capability in diminishing key inflammatory markers, indicating its prospective therapeutic significance in lung transplantation scenarios.

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The apnea test, employed for brain death assessment, aims to demonstrate the absence of respiratory drive due to hypercapnia. The tracheal oxygen insufflation apnea test mode (I-AT) involves disconnecting the patient from invasive mechanical ventilation (iMV) for approximately 8 minutes while maintaining oxygenation. This test supports the diagnosis of brain death based on a specified increase in PaCO2. Common complications include hypoxemia and hemodynamic instability, and lung collapse-induced reduction in end-expiratory lung volume (EELV). In our case series utilizing electrical impedance tomography (EIT), we observed that continuous positive airway pressure during the apnea test (CPAP-AT) effectively mitigated lung collapse. This resulted in improved pulmonary strain compared to the disconnection of iMV. These findings suggest the potential benefits of routine CPAP-AT, particularly for potential lung donors, emphasizing the relevance of our study in providing quantitative insights into EELV loss and its association with pulmonary strain and potential lung injury.

La prueba de apnea es una técnica diagnóstica ampliamente utilizada para la evaluación de la muerte cerebral, con el objetivo de demostrar la ausencia de impulso respiratorio debido a la hipercapnia. La variante de la prueba de apnea con insuflación de oxígeno traqueal (I-AT) implica desconectar al paciente de la ventilación mecánica invasiva (iVM) durante aproximadamente 8 minutos, manteniendo la oxigenación mediante un catéter de insuflación. Esta prueba respalda el diagnóstico de muerte cerebral cuando se determina un aumento de la PaCO 2 superior a 20 mmHg en comparación con el valor inicial o un nivel de PaCO 2 superior a 60 mmHg al final de la prueba. En nuestra serie de casos, la implementación de la tomografía de impedancia eléctrica (EIT) reveló que la prueba de apnea con presión positiva continua (CPAPAT) mitiga eficazmente el colapso pulmonar. Este enfoque resulta en una mejora en la tensión pulmonar en comparación con la desconexión de iMV, demostrando su relevancia en el contexto de potenciales donantes de pulmones.

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Objective: To identify the profile of organ and tissue donors at a university hospital in southern Brazil. Method: This is a cross-sectional research with descriptive analysis. Data collection was carried out on 480 medical records of effective brain-dead organ donors at a University Hospital in Southern Brazil. Results: The most recurrent cause of death was Hemorrhagic Cerebrovascular Accident (HCVA), with 37.1% (n=176). Of these cases, 55.9% (n=268) were men, 71.4% (n=342) were White, and the most donated organ was the kidney, with 89.8% (n=430). The average time between the first brain death test and the beginning of organ removal was 26 hours. Conclusions: The profile of the effective organ donor is male, White, with an average age of 40 years, and overweight. (AU)

Objetivo: Identificar el perfil de los donantes de órganos y tejidos en un hospital universitario del Sur de Brasil. Método: Investigación trans-versal con análisis descriptivo. La recolección de datos se realizó en 480 prontuarios de donantes efectivos de órganos en muerte encefálica en un Hospital Universitario del Sur de Brasil. Resultados: La causa de muerte más recurrente fue Accidente Cerebrovascular Hemorrágico, con un 37,1% (n=176). El 55,9% (n=268) eran hombres, 71,4% (n=342) eran de raza blanca, y el órgano más donado fue el riñón, con un 89,8% (n=430). El tiempo promedio entre la primera prueba de Muerte Encefálica y el inicio de la extracción de los órganos fue de 26 horas. Conclusión: El perfil del donante efectivo de órganos es masculino, blanco, con edad promedio de 40 años y con sobrepeso. (AU)

Objetivo: Identificar o perfil dos doadores de órgãos e tecidos de um hospital universitário no Sul do Brasil. Método: Pesquisa transversal com análise descritiva. A coleta de dados foi realizada em 480 prontuários de doadores efetivos de órgãos em morte encefálica em um Hospital Universitário do Sul do Brasil. Resultados: A causa de morte mais recorrente foi Acidente Vascular Encefálico Hemorrágico (AVEh), com 37,1% (n=176). Desses casos, 55,9% (n=268) eram do sexo masculino, sendo 71,4% (n 342) da cor branca, e o órgão mais doado foi o rim, com 89,8% (n=430). A média de tempo entre o primeiro teste de morte encefálica e o início da remoção dos órgãos foi de 26 horas. Conclusão: O perfil do doador efetivo de órgãos é do sexo mascu-lino, branco, com idade média de 40 anos e com sobrepeso. (AU)

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INTRODUCTION AND OBJECTIVES: Due to organ shortages, liver transplantation (LT) using donation-after-circulatory-death (DCD) grafts has become more common. There is limited and conflicting evidence on LT outcomes using DCD grafts compared to those using donation-after-brain death (DBD) grafts for patients with hepatocellular carcinoma (HCC). We aimed to summarize the current evidence on the outcomes of DCD-LT and DBD-LT in patients with HCC. MATERIALS AND METHODS: Online databases were searched for studies comparing DCD-LT and DBD-LT outcomes in patients with HCC and a meta-analysis was conducted using fixed- or random-effects models. RESULTS: Five studies involving 487 (33.4%) HCC DCD-LT patients and 973 (66.6%) DBD-LT patients were included. The meta-analysis showed comparable 1-year [relative risk (RR)=0.99, 95%CI:0.95 to 1.03, p=0.53] and 3-year [RR=0.99, 95%CI:0.89 to 1.09, p=0.79] recurrence-free survival. The corresponding 1-year [RR=0.98, 95%CI:0.93 to 1.03, p=0.35] and 3-year [RR=0.94, 95%CI:0.87 to 1.01, p=0.08] patient survival and 1-year [RR=0.91, 95%CI:0.71 to 1.16, p=0.43] and 3-year [RR=0.92, 95%CI:0.67 to 1.26, p=0.59] graft survival were also comparable. There were no significant differences between the two cohorts regarding the tumor characteristics, donor/recipient risk factors and the incidence of post-operative complications, including acute rejection, primary non-function, biliary complications and retransplantation. CONCLUSIONS: Based on the current evidence, it has been found that comparable outcomes can be achieved in HCC patients using DCD-LT compared to DBD-LT, particularly when employing good quality graft, strict donor and recipient selection, and effective surgical management. The decision to utilize DCD-LT for HCC patients should be personalized, taking into consideration the risk of post-LT HCC recurrence. (PROSPERO ID: CRD42023445812).

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BACKGROUND: Ex vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP. METHODS: Male and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis. Heart-lung blocks were kept in cold storage (1 h) and normothermic EVLP carried out (4 h), meanwhile ventilation parameters were recorded. Perfusate was sampled for gas analysis and IL-1ß levels. Leukocyte infiltration, myeloperoxidase presence, IL-1ß gene expression, and long-term release in lung culture (explant) were evaluated. RESULTS: Brain dead females presented a low lung function after BD, compared to BD-males; however, at the end of the EVLP period oxygenation capacity decreased in all BD groups. Overall, ventilation parameters were maintained in all groups. After EVLP lung infiltrate was higher in brain dead females, with higher neutrophil content, and accompanied by high IL-1ß levels, with increased gene expression and concentration in the culture medium (explant) 24 h after EVLP. Female rats presented higher lung inflammation after BD than male rats. Despite maintaining lung function and ventilation mechanics parameters for 4 h, EVLP was not able to alter this profile. CONCLUSION: In this context, further studies should focus on therapeutic measures to control inflammation in donor or during EVLP to increase lung quality.

As there is a shortage of viable lungs for transplantation, methods of lung preservation, such as ex vivo perfusion, are important. This method is a good alternative, as it will not only preserve the lungs, but also enable lung function assessment and treatment of the organs. Studies have showed that lungs from donors of the female sex have greater risk of being rejected, when transplanted to male receptors. However, it's not certain if sex differences in anatomy, physiology and specially in immune response could interfere with the transplant result. Females do present a greater and more efficient immune response to any hazard, however after brain death this control is lost, producing a great inflammatory response as a result. Therefore, in this study we have investigated in more detail the influence of sex on the effects of brain death followed by the preservation method. Thus, we performed a brain death model in males and females rats and placed their lungs in an ex vivo lung perfusion machine. At the end of the experiment, we analyzed lung ventilation, gas exchange, and inflammatory parameters. The obtained data indicated that overall the lung ventilation and gas exchange is maintained by the ex vivo perfusion machine. Also, that lung inflammation is influenced by the sex of the donor; where the lungs from females present greater inflammation compared to the lungs from males.

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OBJECTIVE: To quantitate the impact of heart donation after circulatory death (DCD) donor utilization on both waitlist and post-transplant outcomes in the United States. METHODS: The United Network for Organ Sharing database was queried to identify all adult waitlisted and transplanted candidates between October 18, 2018, and December 31, 2022. Waitlisted candidates were stratified according to whether they had been approved for donation after brain death (DBD) offers only or also approved for DCD offers. The cumulative incidence of transplantation was compared between the 2 cohorts. In a post-transplant analysis, 1-year post-transplant survival was compared between unmatched and propensity-score-matched cohorts of DBD and DCD recipients. RESULTS: A total of 14,803 candidates were waitlisted, including 12,287 approved for DBD donors only and 2516 approved for DCD donors. Overall, DCD approval was associated with an increased sub-hazard ratio (HR) for transplantation and a lower sub-HR for delisting owing to death/deterioration after risk adjustment. In a subgroup analysis, candidates with blood type B and status 4 designation received the greatest benefit from DCD approval. A total of 12,238 recipients underwent transplantation, 11,636 with DBD hearts and 602 with DCD hearts. Median waitlist times were significantly shorter for status 3 and status 4 recipients receiving DCD hearts. One-year post-transplant survival was comparable between unmatched and propensity score-matched cohorts of DBD and DCD recipients. CONCLUSIONS: The use of DCD hearts confers a higher probability of transplantation and a lower incidence of death/deterioration while on the waitlist, particularly among certain subpopulations such as status 4 candidates. Importantly, the use of DCD donors results in similar post-transplant survival as DBD donors.

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Guidelines for brain death/death by neurologic criteria (BD/DNC) determination were revised to provide a consistent and updated approach to BD/DNC evaluation across all ages by the American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine. This article is intended to complement the guidelines and highlight aspects relevant to the critical care community; the actual guidelines should be used to update hospital protocols and dictate clinical practice. Because BD/DNC evaluations are conducted in the ICU, it is essential for members of the critical care community to familiarize themselves with these guidelines. The fundamental concept of BD/DNC has not changed; BD/DNC is permanent loss of function of the brain as a whole, including the brain stem, resulting in coma, brainstem areflexia, and apnea in the setting of an adequate stimulus. The BD/DNC evaluation requires a sufficient observation period to ensure there is no chance of recovery, followed by exclusion of potentially confounding conditions like hypothermia, hypotension, severe metabolic disturbances, or medication effects. Specific guidance is provided for patients who were treated with therapeutic hypothermia or medical or surgical interventions to manage intracranial hypertension. The guidelines outline a structured and meticulous neurologic examination and detail the responses consistent with BD/DNC. A protocol is provided for how to safely perform apnea testing, including modifications needed for patients on extracorporeal membrane oxygenation. Controversial issues such as consent, BD/DNC evaluation in pregnancy, preservation of neuroendocrine function, and primary posterior fossa injuries are addressed. The ultimate goal is to ensure a consistent and accurate approach to BD/DNC evaluation in patients of all ages, fostering public trust in the medical community's ability to determine death. By adhering to these guidelines, critical care clinicians can confidently navigate the challenging aspects of BD/DNC determination.

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Primary cell cultures are essential tools for elucidating the physiopathological mechanisms of the cardiovascular system. Therefore, a primary culture growth protocol of cardiovascular smooth muscle cells (VSMCs) obtained from human abdominal aortas was standardized. Ten abdominal aorta samples were obtained from patients diagnosed with brain death who were organ and tissue donors with family consent. After surgical ablation to capture the aorta, the aortic tissue was removed, immersed in a Custodiol® solution, and kept between 2 and 8 °C. In the laboratory, in a sterile environment, the tissue was fragmented and incubated in culture plates containing an enriched culture medium (DMEM/G/10% fetal bovine serum, L-glutamine, antibiotics and antifungals) and kept in an oven at 37 °C and 5% CO2. The aorta was removed after 24 h of incubation, and the culture medium was changed every six days for twenty days. Cell growth was confirmed through morphological analysis using an inverted optical microscope (Nikon®) and immunofluorescence for smooth muscle alpha-actin and nuclei. The development of the VSMCs was observed, and from the twelfth day, differentiation, long cytoplasmic projections, and adjacent cell connections occurred. On the twentieth day, the morphology of the VSMCs was confirmed by actin fiber immunofluorescence, which is a typical characteristic of VSMCs. The standardization allowed VSMC growth and the replicability of the in vitro test, providing a protocol that mimics natural physiological environments for a better understanding of the cardiovascular system. Its use is intended for investigation, tissue bioengineering, and pharmacological treatments.

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