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Despite the promising role of renal replacement therapy (RRT) in acute liver failure (ALF), high‐risk patients need liver transplantation and remain at risk for death due to cerebral complications. The objective of this study was to report outcomes of living donor liver transplantation (LDLT) for ALF with perioperative RRT. This was a single‐center retrospective cohort study. Out of 1167 LDLTs, 24 patients had ALF and met the King's College criteria for transplantation. They were categorized into no‐RRT (n = 13) and RRT (n = 11) groups. We looked at 1‐year posttransplant survival in these patients. The median serum ammonia level at the time of transplant in the no‐RRT and RRT groups was 259.5 mcg/dL (222.7–398) and 70.6 mcg/dL (58.1–92.6) (p = 0.005). In the RRT group, serum ammonia level < 100 mcg/dL was achieved in all patients. Seven (53.8%) patients in the no‐RRT group and 11/11 (100%) in the RRT group were extubated and regained full consciousness after LDLT (p = 0.013). The 90‐day mortality was 6/13 (46.1%) and 2/11 (18.1%) (p = 0.211). There was no brainstem herniation‐related mortality in the RRT group, that is, 5/13 (38.4%) and 0/11 (0%) (p = 0.030). The 1‐year posttransplant survival was also significantly higher in the RRT group (p = 0.031). The use of RRT lowers serum ammonia levels and might reduce posttransplant mortality due to brainstem herniation. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion The Organ Care System (OCS) (Transmedics, Andover, MA) reduces cold ischemic time of donor hearts by producing a normothermic beating state during ex vivo perfusion, enabling extended ex situ intervals, which potentially increases donor pool. We aimed to compare outcomes in utilization of OCS and conventional cold storage technique.Consecutive heart transplants following brain death at our institution between May 2022 and July 2023 were analyzed. Recipients were divided into those receiving hearts preserved with OCS [N = 15] and those with conventional cold storage (Control, N = 27), with OCS utilization when anticipated ischemic time was more than 4 h. Pre‐transplant characteristics and transplant outcomes were compared.OCS utilization allowed a significant increase in distance traveled for heart retrieval (OCS, 624 ± 269 vs. Control, 153 ± 128 miles, p < 0.001), with longer mean total preservation times (6.2 ± 1.1 vs 2.6 ± 0.6 h, p < 0.001). All but one patient displayed a general decrease or plateau in lactate throughout perfusion time by OCS. Both groups experienced similar rates of severe primary graft dysfunction (OCS, 6.7% [N = 1] vs. Control, 11.1% [N = 3], p = 0.63), with 100% in‐hospital survival in the OCS group compared to 96.3% in the Control group (p = 0.34). Kaplan–Meier survival analysis showed that estimated one‐year survival were comparable (OCS, 93.3 ± 6.4% vs. Control, 88.9 ± 6.0%, p = 0.61).With a mean preservation time of around 6 h and distance covered of over 600 miles, our results using OCS indicate a potential to safely increase the quantity and viability of accessible organs, thus broadening the donor pool without negatively affecting outcomes. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD) causes slow death in brain cells due to shrinkage of brain cells which is more prevalent in older people. In most cases, the symptoms of AD are mistaken as age-related stresses. The most widely utilized method to detect AD is Magnetic Resonance Imaging (MRI). Along with Artificial Intelligence (AI) techniques, the efficacy of identifying diseases related to the brain has become easier. But, the identical phenotype makes it challenging to identify the disease from the neuro-images. Hence, a deep learning method to detect AD at the beginning stage is suggested in this work. The newly implemented "Enhanced Residual Attention with Bi-directional Long Short-Term Memory (Bi-LSTM) (ERABi-LNet)" is used in the detection phase to identify the AD from the MRI images. This model is used for enhancing the performance of the Alzheimer's detection in scale of 2–5%, minimizing the error rates, increasing the balance of the model, so that the multi-class problems are supported. At first, MRI images are given to "Residual Attention Network (RAN)", which is specially developed with three convolutional layers, namely atrous, dilated and Depth-Wise Separable (DWS), to obtain the relevant attributes. The most appropriate attributes are determined by these layers, and subjected to target-based fusion. Then the fused attributes are fed into the "Attention-based Bi-LSTM". The final outcome is obtained from this unit. The detection efficiency based on median is 26.37% and accuracy is 97.367% obtained by tuning the parameters in the ERABi-LNet with the help of Modified Search and Rescue Operations (MCDMR-SRO). The obtained results are compared with ROA-ERABi-LNet, EOO-ERABi-LNet, GTBO-ERABi-LNet and SRO-ERABi-LNet respectively. The ERABi_LNet thus provides enhanced accuracy and other performance metrics compared to such deep learning models. The proposed method has the better sensitivity, specificity, F1-Score and False Positive Rate compared with all the above mentioned competing models with values such as 97.49%.97.84%,97.74% and 2.616 respective;y. This ensures that the model has better learning capabilities and provides lesser false positives with balanced prediction. [ABSTRACT FROM AUTHOR]

Background: The demand for organ transplants, both globally and in South Korea, substantially exceeds the supply, a situation that might have been aggravated by the enactment of the Life-Sustaining Treatment Decision Act (LSTDA) in February 2018. This legislation may influence emergency medical procedures and the availability of organs from brain-dead donors. This study aimed to assess LSTDA's impact, introduced in February 2018, on organ donation status in out-of-hospital cardiac arrest (OHCA) patients in a metropolitan city and identified related factors. Methods: We conducted a retrospective analysis of a regional cardiac arrest registry. This study included patients aged 16 or older with cardiac arrest and a cerebral performance category (CPC) score of 5 from January 2015 to December 2022. The exclusion criteria were CPC scores of 1–4, patients under 16 years, and patients declared dead or transferred from emergency departments. Logistic regression analysis was used to analyse factors affecting organ donation. Results: Of the 751 patients included in this study, 47 were organ donors, with a median age of 47 years. Before the LSTDA, there were 30 organ donations, which declined to 17 after its implementation. In the organ donation group, the causes of cardiac arrest included medical (34%), hanging (46.8%), and trauma (19.2%). The adjusted odds ratio for organ donation before the LSTDA implementation was 6.12 (95% CI 3.09–12.12), with non-medical aetiology as associated factors. Conclusion: The enactment of the LSTDA in 2018 in South Korea may be linked to reduced organ donations among patients with OHCA, underscoring the need to re-evaluate the medical and legal aspects of organ donation, especially considering end-of-life care decisions. [ABSTRACT FROM AUTHOR]

Subclinical research of xenotransplantation involves xenotransplantation trial using brain death donors, which is an important intermediate step from basic research and animal experiments to the clinical application of xenotransplantation. It provides necessary data support for the safety and efficacy of xenotransplantation. In order to promote the safe, orderly, scientific and standardized development of subclinical research on xenotransplantation, the Xenotransplantation Group of Branch of Organ Transplantation of Chinese Medical Association formulated the “Expert Consensus on Subclinical Research of Xenotransplantation (2024 Edition)” based on relevant laws and regulations. The consensus includes aspects such as the selection of donor pigs, recipient selection criteria, legal and ethical requirements, determination of trial termination time, family informed consent system, and brain death determination standards. [ABSTRACT FROM AUTHOR]

The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to offer livers from deceased donors to patients on the national waiting list based, for most patients, on calculated transplant benefit. Before NLOS, livers were offered to transplant centres by geographic donor zones and, within centres, by estimated recipient need for a transplant. UK Transplant Registry data on patient registrations and transplants were analysed to build statistical models for survival on the list (M1) and survival post-transplantation (M2). A separate cohort of registrations – not seen by the models before – was analysed to simulate what liver allocation would have been under M1, M2 and a transplant benefit score (TBS) model (combining both M1 and M2), and to compare these allocations to what had been recorded in the UK Transplant Registry. The number of deaths on the waiting list and patient life years were used to compare the different simulation scenarios and to select the optimal allocation model. Registry data were monitored, pre- and post-NLOS, to understand the performance of the scheme. The TBS was identified as the optimal model to offer donation after brain death (DBD) livers to adult and large paediatric elective recipients. In the first 2 years of NLOS, 68% of DBD livers were offered using the TBS to this type of recipient. Monitoring data indicate that mortality on the waiting list post-NLOS significantly decreased compared with pre-NLOS (p <0.0001), and that patient survival post-listing was significantly greater post- compared to pre-NLOS (p = 0.005). In the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, delivering on the scheme's objectives. The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to increase transparency of the deceased donor liver offering process, maximise the overall survival of the waiting list population, and improve equity of access to liver transplantation. To our knowledge, it is the first scheme that offers organs based on statistical prediction of transplant benefit: the transplant benefit score. The results are important to the transplant community – from healthcare practitioners to patients – and demonstrate that, in the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, thus delivering on the scheme's objectives. The scheme continues to be monitored to ensure that the transplant benefit score remains up-to-date and that signals that suggest the possible disadvantage of some patients are investigated. [Display omitted] • In 2018 the UK introduced a benefit-based scheme to offer deceased donor livers. • Benefit is predicted using a patient's need for, and the utility of, a transplant. • The novelty of the scheme relates to the incorporation of predicted utility. • The scheme reduces waiting-list mortality and preserves post-transplant outcomes. • Life-year gain from transplantation is maximised for the waiting list population. [ABSTRACT FROM AUTHOR]

This article explores the ethical considerations surrounding the use of CPR for organ preservation after brain death. It identifies two main barriers to accepting CPR for this purpose: misunderstanding of organ donation authorization and moral concerns. The author argues that requiring explicit consent for CPR during donor management in the ICU can address these barriers and help maintain public trust. The article emphasizes the importance of transparency and understanding in organ donation processes, and suggests that obtaining consent can address moral concerns, respect cultural and religious needs, and prevent misunderstandings and feelings of distrust. [Extracted from the article]

The article explores the ethical implications of resuscitation for organ preservation in brain dead patients or those being tested for brain death. It acknowledges the lack of consensus on this issue, with proponents arguing that resuscitation can honor the wishes of donors and benefit organ recipients, while opponents express concerns about exploiting the donor and causing distress to families. The article examines various ethical arguments and principles, emphasizing the importance of respecting autonomy and maximizing utility. It concludes with recommendations based on these considerations. The document provided is a list of references for articles related to organ donation and ethical considerations in the surgical ICU, offering valuable insights for researchers and healthcare professionals interested in these topics. [Extracted from the article]

Regardless of the type, extracorporeal membrane oxygenation (ECMO) requires the use of large intravascular cannulas and results in multiple abnormalities including non-physiologic blood flow, hemodynamic perturbation, rapid changes in blood oxygen and carbon dioxide levels, coagulation abnormalities, and a significant systemic inflammatory response. Among other sequelae, neurologic complications are an important source of mortality and long-term morbidity. The frequency of neurologic complications varies and is likely underreported due to the high mortality rate. Neurologic complications in patients supported by ECMO include ischemic and hemorrhagic stroke, hypoxic brain injury, intracranial hemorrhage, and brain death. In addition to the disease process that necessitates ECMO, cannulation strategies and physiologic disturbances influence neurologic outcomes in this high-risk population. For example, the overall documented rate of neurologic complications in the venovenous ECMO population is lower, but a higher rate of intracranial hemorrhage exists. Meanwhile, in the venoarterial ECMO population, ischemia and global hypoperfusion seem to compose a higher percentage of neurologic complications. In what follows, the literature is reviewed to discuss the pathophysiology, incidence, risk factors, and outcomes related to short-term neurologic complications in patients supported by ECMO. [ABSTRACT FROM AUTHOR]

We aimed to assess the impact of hospital characteristics on the outcomes of detected possible brain-dead donors, in our organ procurement network in Iran. Data was collected through twice-daily calls with 57 hospitals' intensive care units and emergency departments over 1 year. The donation team got involved when there was suspicion of brain death before the hospital officially declared it. The data was categorized by hospital size, presence of neurosurgery/trauma departments, ownership, and referral site. Out of 813 possible donors, 315 were declared brain dead, and 203 were eligible for donation. After conducting family interviews (consent rate: 62.2%), 102 eligible donors became actual donors (conversion rate: 50.2%). While hospital ownership and the presence of trauma/neurosurgery care did not affect donation, early referral from the emergency department had a positive effect. Therefore, we strongly recommend prioritizing possible donor identification in emergency rooms and involving the organ donation team as early as possible. The use of twice-daily calls for donor identification likely contributed to the consistency in donation rates across hospitals, as this approach involves the donation team earlier and mitigates the impact of hospital characteristics. Early detection of possible donors from the emergency department is crucial in improving donation rates. [ABSTRACT FROM AUTHOR]

Stroke causes death of brain tissue leading to long-term deficits. Behavioral evidence from neurorehabilitative therapies suggest learning-induced neuroplasticity can lead to beneficial outcomes. However, molecular and cellular mechanisms that link learning and stroke recovery are unknown. We show that in a mouse model of stroke, which exhibits enhanced recovery of function due to genetic perturbations of learning and memory genes, animals display activity-dependent transcriptional programs that are normally active during formation or storage of new memories. The expression of neuronal activity-dependent genes are predictive of recovery and occupy a molecular latent space unique to motor recovery. With motor recovery, networks of activity-dependent genes are co-expressed with their transcription factor targets forming gene regulatory networks that support activity-dependent transcription, that are normally diminished after stroke. Neuronal activity-dependent changes at the circuit level are influenced by interactions with microglia. At the molecular level, we show that enrichment of activity-dependent programs in neurons lead to transcriptional changes in microglia where they differentially interact to support intercellular signaling pathways for axon guidance, growth and synaptogenesis. Together, these studies identify activity-dependent transcriptional programs as a fundamental mechanism for neural repair post-stroke. A transcriptomic study at different time points with modulation of learning and memory genes after stroke shows robust expression of activity dependent transcriptional programs during motor recovery that are normally expressed during memory formation. [ABSTRACT FROM AUTHOR]

Mutations in the PSEN genes are the major cause of familial Alzheimer's disease, and presenilin (PS) is the catalytic subunit of γ-secretase, which cleaves type I transmembrane proteins, including the amyloid precursor protein (APP) to release Aβ peptides. While PS plays an essential role in the protection of neuronal survival, PSEN mutations also increase the ratio of Aβ42/Aβ40. Thus, it remains unresolved whether PSEN mutations cause AD via a loss of its essential function or increases of Aβ42/Aβ40. Here, we test whether the knockin (KI) allele of Psen1 L435F, the most severe FAD mutation located closest to the active site of γ-secretase, causes age-dependent cortical neurodegeneration independent of Aβ by crossing various Psen mutant mice to the App-null background. We report that removing Aβ completely through APP deficiency has no impact on the age-dependent neurodegeneration in Psen mutant mice, as shown by the absence of effects on the reduced cortical volume and decreases of cortical neurons at the ages of 12 and 18 mo. The L435F KI allele increases Aβ42/Aβ40 in the cerebral cortex while decreasing de novo production and steady-state levels of Aβ42 and Aβ40 in the presence of APP. Furthermore, APP deficiency does not alleviate elevated apoptotic cell death in the cerebral cortex of Psen mutant mice at the ages of 2, 12, and 18 mo, nor does it affect the progressive microgliosis in these mice. Our findings demonstrate that Psen1 mutations cause age-dependent neurodegeneration independent of Aβ, providing further support for a loss-of-function pathogenic mechanism underlying PSEN mutations. [ABSTRACT FROM AUTHOR]

Breast cancer is the most frequent malignancy in women, constituting 15.2% of all new cancers diagnosed in the United States. Distant breast cancer metastasis accounts for the majority of breast cancer-related deaths; brain metastasis is the third most common site for metastatic breast cancer but is associated with worst prognosis of approximately eight months of survival. Current treatment options for breast cancer brain metastasis (BCBM) are limited and ineffective. To help identify new and effective therapies for BCBM, it is important to investigate the mechanisms by which breast cancer cells metastasize to the brain and thrive in the brain microenvironment. To this end, studies have reported that primary breast tumor cells can prime brain microenvironmental cells, including, astrocytes and microglia, to promote the formation of BCBM through the release of extracellular vesicle-microRNAs (miRNAs). Breast tumor-derived miRNAs can also promote breast cancer cell invasion through the blood-brain barrier by disrupting the integrity of the brain microvascular endothelial cells. In this review, we summarize current literature on breast cancer-derived BCBMpromoting miRNAs, cover their roles in the complex steps of BCBM particularly their interactions with microenvironmental cells within the brain metastatic niche, and finally discuss their therapeutic applications in the management of BCBM. [ABSTRACT FROM AUTHOR]

Brain death (BD) is a complex medical state that triggers systemic disturbances and a cascade of pathophysiological processes. This condition significantly impairs both kidney function and structural integrity, thereby presenting considerable challenges to graft viability and the long-term success of transplantation endeavors. Tacrolimus (FK506), an immunosuppressive drug, was used in this study to assess its impact as a pretreatment on brain deathinduced renal injury. This study aimed to investigate changes associated with brain death-induced renal injury in a 4-month-old female porcine model. The experimental groups included brain death placebo-pretreated (BD; n = 9), brain death tacrolimus-pretreated using the clinical dose of 0.25 mg/kg the day before surgery, followed by 0.05 mg/kg/day 1 hour before the procedure (BD + FK506; n = 8), and control (ctrl, n = 7) piglets, which did not undergo brain death induction. Furthermore, we aimed to assess the effect of FK506 on these renal alterations through graft preconditioning. We hypothesized that immunosuppressive properties of FK506 reduce tissue inflammation and preserve the glycocalyx. Our findings revealed a series of interconnected events triggered by BD, leading to a deterioration of renal function and increased proteinuria, increased apoptosis in the vessels, glomeruli and tubules, significant leukocyte infiltration into renal tissue, and degradation of the glycocalyx in comparison with ctrl group. Importantly, treatment with FK506 demonstrated significant efficacy in attenuating these adverse effects. FK506 helped reduce apoptosis, maintain glycocalyx integrity, regulate neutrophil infiltration, and mitigate renal injury following BD. This study offers new insights into the pathophysiology of BD-induced renal injury, emphasizing the potential of FK506 pretreatment as a promising therapeutic intervention for organ preservation, through maintaining endothelial function with the additional benefit of limiting the risk of rejection. [ABSTRACT FROM AUTHOR]

Static cold storage (SCS) remains the gold standard for preserving donor hearts before transplantation but is associated with ischaemia, anaerobic metabolism, and organ injuries, leading to patient morbidity and mortality. We aimed to evaluate whether continuous, hypothermic oxygenated machine perfusion (HOPE) of the donor heart is safe and superior compared with SCS. We performed a multinational, multicentre, randomised, controlled, open-label clinical trial with a superiority design at 15 transplant centres across eight European countries. Adult candidates for heart transplantation were eligible and randomly assigned in a 1:1 ratio. Donor inclusion criteria were age 18–70 years with no previous sternotomy and donation after brain death. In the treatment group, the preservation protocol involved the use of a portable machine perfusion system ensuring HOPE of the resting donor heart. The donor hearts in the control group underwent ischaemic SCS according to standard practices. The primary outcome was time to first event of a composite of either cardiac-related death, moderate or severe primary graft dysfunction (PGD) of the left ventricle, PGD of the right ventricle, acute cellular rejection at least grade 2R, or graft failure (with use of mechanical circulatory support or re-transplantation) within 30 days after transplantation. We included all patients who were randomly assigned, fulfilled inclusion and exclusion criteria, and received a transplant in the primary analysis and all patients who were randomly assigned and received a transplant in the safety analyses. This trial was registered with ClicalTrials.gov (NCT03991923) and is ongoing. A total of 229 patients were enrolled between Nov 25, 2020, and May 19, 2023. The primary analysis population included 204 patients who received a transplant. There were no patients who received a transplant lost to follow-up. All 100 donor hearts preserved with HOPE were transplantable after perfusion. The primary endpoint was registered in 19 (19%) of 101 patients in the HOPE group and 31 (30%) of 103 patients in the SCS group, corresponding to a risk reduction of 44% (hazard ratio 0·56; 95% CI 0·32–0·99; log-rank test p=0·059). PGD was the primary outcome event in 11 (11%) patients in the HOPE group and 29 (28%) in the SCS group (risk ratio 0·39; 95% CI 0·20–0·73). In the HOPE group, 63 (65%) patients had a reported serious adverse event (158 events) versus 87 (70%; 222 events) in the SCS group. Major adverse cardiac transplant events were reported in 18 (18%) and 33 (32%) patients in the HOPE and SCS group (risk ratio 0·56; 95% CI 0·34–0·92). Although there was not a significant difference in the primary endpoint, the 44% risk reduction associated with HOPE was suggested to be a clinically meaningful benefit. Post-transplant complications, measured as major adverse cardiac transplant events, were reduced. Analysis of secondary outcomes suggested that HOPE was beneficial in reducing primary graft dysfunction. HOPE in donor heart preservation addresses the existing challenges associated with graft preservation and the increasing complexity of donors and heart transplantation recipients. Future investigation will help to further elucidate the benefit of HOPE. XVIVO Perfusion. [ABSTRACT FROM AUTHOR]

This article explores the characteristics and diagnosis of epithelioid glioblastoma (eGB), a rare and aggressive form of glioblastoma that primarily affects young adult males. The patient in the case study presented with symptoms such as headache and vomiting, and imaging revealed a brain mass with peripheral edema. Cerebrospinal fluid cytology confirmed the presence of eGB through the identification of neoplastic cells with distinct features. The article also discusses the cellular morphology and genetic alterations associated with eGB, as well as the potential effectiveness of certain inhibitors in its treatment. Overall, the study emphasizes the importance of considering eGB in patient care and prognosis. [Extracted from the article]

Many antiseizure medications cause apoptotic cell death in developing brains. The newer antiseizure medication lacosamide is increasingly used in neonates and infants. Neurotoxicity of lacosamide and its combination with levetiracetam was studied in neonatal mice. Animals received single or repeat injections of saline, phenobarbital (75mg/kg), lacosamide (20–40mg/kg), levetiracetam (100mg/kg), lacosamide (40mg/kg) + levetiracetam (100mg/kg) and euthanized at 6 to 30 hours. Cells undergoing apoptosis were increased in the brains of phenobarbital‐treated animals. Densities of apoptotic profiles following lacosamide and levetiracetam treatment did not differ from saline‐treated controls. Findings suggest that lacosamide, levetiracetam and their combination do not cause apoptosis in developing mouse brains. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) is used in critically ill children with cardiac and/or respiratory failure. Use is increasing in children with high‐risk comorbidities. Reasons children do not survive ECMO are poorly described. Aims: Describe characteristics and cause of death, compare mortality in children with high‐risk comorbidities, evaluate mortality trends over a decade. Method: All children <18 years old who received ECMO at this institution from 1 January 2011 to 31 December 2020 were described and categorised by outcome: died on or <48 h post‐ECMO, died ≥48 h post‐ECMO, survived to hospital discharge. Children who did not survive ECMO (DNSE) were categorised to: ECMO withdrawal for irrecoverable original condition, withdrawal for poor prognosis neurological condition, brain death, withdrawal for poor prognosis with multiple complex conditions, and unsupportable. Poison regression was used to analyse survival trends. Results: Four hundred twenty‐eight children received ECMO, 19% DNSE, 14% died ≥48 h post‐ECMO and 67% survived. ECMO was electively withdrawn for irrecoverable original condition (39%), poor prognosis for neurological condition (32%) or multiple complex conditions (18%). One hundred twenty‐two children had ≥1 high‐risk comorbidity. Children with genetic syndromes (58%), risk‐adjusted congenital heart surgery score‐1 ≥4 (53%), primary immunodeficiency (50%) had lower hospital survival. No children with malignancy/bone marrow transplant survived to hospital discharge. Overall hospital survival was 67%, with no significant change during the study period (P‐trend = 0.99). Conclusion: Children who DNSE have therapy electively withdrawn for irrecoverable disease or poor prognosis. Children with high‐risk comorbidities have a reasonable chance of survival. This study informs clinicians ECMO may be a therapeutic option. [ABSTRACT FROM AUTHOR]

The literature on the determination of death has often if not always assumed that the concept of human death should be defined in terms of the end of the human organism. I argue that this broadly biological conceptualization of human death cannot constitute a basis for agreement in a pluralistic society characterized by a variety of reasonable views on the nature of our existence as embodied beings. Rather, following Robert Veatch, I suggest that we must define death in moralized terms, as the loss of an especially significant sort of moral standing. Departing from Veatch, however, I argue that we should not understand death in terms of the loss of all moral status whatsoever. Rather, I argue, what we should argue about, when we argue about death, is when and why people lose their rights-claims to the protection and promotion of their basic bodily functioning. [ABSTRACT FROM AUTHOR]

Our previous study revealed that over 50% of recipients with pretransplant impaired glucose tolerance (IGT) improved to normal glucose tolerance after kidney transplantation. However, the mechanism is unclear. We aimed to investigate whether the changes in glucose tolerance are associated with β-cell function and insulin resistance in Japanese kidney transplant recipients with pretransplant IGT. Of the 265 recipients who received kidney transplantation, 54 with pretransplant IGT were included. We divided the recipients into improvement and nonimprovement groups according to the change in the area under the curve for glucose obtained from the oral glucose tolerance test (OGTT). β-Cell function was estimated by the insulin secretion sensitivity index-2 (ISSI-2) and the disposition index (DI). Insulin resistance was estimated by the Matsuda index (MI) and the homeostasis model assessment of insulin resistance (HOMA-IR). ISSI-2 and DI increased significantly after transplantation in the improved group (P < 0.01, P < 0.05, respectively), but not in the nonimproved group. ΔISSI-2 and ΔDI were significantly and positively associated with pretransplant 60-min OGTT plasma glucose levels (both P < 0.01). There were no differences in MI or HOMA-IR between these two groups after transplantation. In recipients not on pretransplant dialysis, a significant negative association was found between Δblood urea nitrogen (BUN) and ΔDI (correlation coefficient = −0.48, P < 0.05). In pretransplant IGT recipients, improvements in glucose tolerance after kidney transplantation were linked to improvements in β-cell function. The higher the 60-min OGTT plasma glucose level, the greater the improvement in posttransplant β-cell function. Improvements in BUN after transplantation were associated with improvements in β-cell function. NEW & NOTEWORTHY: In recipients with pretransplant impaired glucose tolerance, improvements in glucose tolerance after kidney transplantation were associated with improvements in β-cell function. The higher the pretransplant 60-min OGTT plasma glucose level, the greater the improvement in posttransplant β-cell function. Although glucose tolerance is known to be impaired after transplantation, the present study focused on the reason for the improvement in glucose tolerance rather than the development of posttransplantation diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Cerebral ischemia/reperfusion injury (CIRI) is still a complicated disease with high fatality rates worldwide. Transmembrane Protein 79 (TMEM79) regulates inflammation and oxidative stress in some other diseases. Methods: CIRI mouse model was established using C57BL/6J mice through middle cerebral artery occlusion-reperfusion (MCAO/R), and BV2 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) to simulate CIRI. Brain tissue or BV2 cells were transfected or injected with lentivirus-carried TMEM79 overexpression vector. The impact of TMEM79 on CIRI-triggered oxidative stress was ascertained by dihydroethidium (DHE) staining and examination of oxidative stress indicators. Regulation of TMEM79 in neuronal apoptosis and inflammation was determined using TUNEL staining and ELISA. Results: TMEM79 overexpression mitigated neurological deficit induced by MCAO/R and decreased the extent of cerebral infarct. TMEM79 prevented neuronal death in brain tissue of MCAO/R mouse model and suppressed inflammatory response by reducing inflammatory cytokines levels. Moreover, TMEM79 significantly attenuated inflammation and oxidative stress caused by OGD/R in BV2 cells. TMEM79 facilitated the activation of Nrf2 and inhibited NLRP3 and caspase-1 expressions. Rescue experiments indicated that the Nrf2/NLRP3 signaling pathway mediated the mitigative effect of TMEM79 on CIRI in vivo and in vitro. Conclusion: Overall, TMEM79 was confirmed to attenuate CIRI via regulating the Nrf2/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Donation after circulatory death (DCD) has reemerged as a method of expanding the donor heart pool. Given the high waitlist mortality of multiorgan heart candidates, we evaluated waitlist outcomes associated with willingness to consider DCD offers and post-transplant outcomes following DCD transplant for these candidates. We identified adult multiorgan heart candidates and recipients between January 1, 2020 and March 31, 2023 nationally. Among candidates that met inclusion criteria, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider DCD offers. Among recipients of DCD versus brain death (DBD) transplants, we compared perioperative outcomes and post-transplant survival. Of 1,802 heart-kidney, 266 heart-liver, and 440 heart-lung candidates, 15.8%, 12.4%, and 31.1%, respectively, were willing to consider DCD offers. On adjusted analysis, willingness to consider DCD offers was associated with higher likelihood of transplant for all multiorgan heart candidates and decreased likelihood of waitlist deterioration for heart-lung candidates. Of 1,100 heart-kidney, 173 heart-liver, and 159 heart-lung recipients, 5.4%, 2.3%, and 2.5%, respectively, received DCD organs. Recipients of DCD and DBD heart-kidney transplants had a similar likelihood of perioperative outcomes and 1-year survival. All other DCD multiorgan heart recipients have survived to the last follow-up. Multiorgan heart candidates who were willing to consider DCD offers had favorable waitlist outcomes, and heart-kidney recipients of DCD transplants had similar post-transplant outcomes to recipients of DBD transplants. We recommend the use of DCD organs to increase the donor pool for these high-risk candidates. [ABSTRACT FROM AUTHOR]

Background and Aims: Biopsy‐proven severe graft steatosis is associated with adverse outcomes after liver transplantation. The concomitant presence of metabolic risk factors might further increase this risk. We studied the association between graft steatosis and metabolic risk factors in the donor, with recipient outcomes after liver transplantation. Methods: We analyzed data from all consecutive first adult full‐graft donation after brain death (DBD) liver transplantations performed in the Eurotransplant region between 2010 and 2020. The presence of graft steatosis and metabolic risk factors was assessed through a review of donor (imaging) reports, and associations with recipient retransplantation‐free survival were studied through survival analyses. Results: Of 12 174 transplantations, graft steatosis was detected in 2689 (22.1%), and donor diabetes mellitus (DM), hypertension, and dyslipidemia were present in 1245 (10.2%), 5056 (41.5%), and 524 (4.3%). In multivariable Cox regression analysis, graft steatosis (adjusted HR [aHR] 1.197, p < 0.001) and donor DM (aHR 1.157, p = 0.004) were independently associated with impaired retransplantation‐free survival. Graft steatosis and donor DM conferred an additive risk of retransplantation or death (DM alone, aHR: 1.156 [p = 0.0185]; steatosis alone, aHR: 1.200 [p < 0.001]; both steatosis and DM, aHR: 1.381 [p < 0.001]). Findings were consistent in sensitivity analyses focusing on retransplantation‐free survival within 7 days. Conclusions: Graft steatosis and donor diabetes mellitus additively increase the risk of retransplantation or death in adult DBD liver transplantation. Future studies should focus on methods to assess and improve the quality of these high‐risk grafts. Until such time, caution should be exercised when considering these grafts for transplantation. [ABSTRACT FROM AUTHOR]

Background: Efforts to address the shortage of donor organs include increasing the use of renal allografts from donors after circulatory death (DCD). While warm ischemia time (WIT) is thought to be an important factor in DCD kidney evaluation, few studies have compared the relationship between WIT and DCD kidney outcomes, and WIT acceptance practices remain variable. Methods: We conducted a single‐center retrospective review of all adult patients who underwent deceased donor kidney transplantation from 2000 to 2021. We evaluated the impact of varied functional warm ischemia time (fWIT) in controlled DCD donors by comparing donor and recipient characteristics and posttransplant outcomes between high fWIT (>60 min), low fWIT (≤60 min), and kidneys transplanted from donors after brain death (DBD). Results: Two thousand eight hundred eleven patients were identified, 638 received low fWIT DCD, 93 received high fWIT DCD, and 2080 received DBD kidneys. There was no significant difference in 5‐year graft survival between the DCD low fWIT, high fWIT, and DBD groups, with 84%, 83%, and 83% of grafts functioning, respectively. Five‐year patient survival was 91% in the low fWIT group, 92% in the high fWIT group, and 90% in the DBD group. An increase in kidney donor risk index (KDRI) (HR 3.37, 95% CI = 2.1–5.7) and high CIT compared to low CIT (HR 2.12, 95% CI = 1.4–3.1) have higher hazard ratios for 1‐year graft failure. Conclusions: Increased acceptance of kidneys from selected DCD donors with prolonged fWIT may present an opportunity to increase kidney utilization while preserving outcomes. Our group specifically prioritizes the use of kidneys from younger donors, with lower KDPI, and without acute kidney injury, or risk factors for underlying chronic kidney disease. [ABSTRACT FROM AUTHOR]

Introduction: Donation after circulatory death (DCD) donors are becoming an important source of organs for heart‐transplantation (HT), but there are limited data regarding their use in multiorgan‐HT. Methods: Between January 2020 and June 2023, we identified 87 adult multiorgan‐HTs performed using DCD‐donors [77 heart–kidney, 6 heart–lung, 4 heart–liver] and 1494 multiorgan‐HTs using donation after brain death (DBD) donors (1141 heart–kidney, 165 heart–lung, 188 heart–liver) in UNOS. For heart–kidney transplantations (the most common multiorgan‐HT combination from DCD‐donors), we also compared donor/recipient characteristics, and early outcomes, including 6‐month mortality using Kaplan–Meier (KM) and Cox hazards‐ratio (Cox‐HR). Results: Use of DCD‐donors for multiorgan‐HTs in the United States increased from 1% in January to June 2020 to 12% in January–June 2023 (p < 0.001); but there was a wide variation across UNOS regions and center volumes. Compared to recipients of DBD heart–kidney transplantations, recipients of DCD heart–kidney transplantations were less likely to be of UNOS Status 1/2 at transplant (35.06% vs. 69.59%) and had lower inotrope use (22.08% vs. 43.30%), lower IABP use (2.60% vs. 26.29%), but higher durable CF‐LVAD use (19.48% vs. 12.97%), all p < 0.01. Compared to DBD‐donors, DCD‐donors used for heart–kidney transplantations were younger [28(22–34) vs. 32(25–39) years, p = 0.004]. Recipients of heart–kidney transplantations from DCD‐donors and DBD‐donors had similar 6‐month survival using both KM analysis, and unadjusted and adjusted Cox‐HR models, including in propensity matched cohorts. Rates of PGF and in‐hospital outcomes were also similar. Conclusions: Use of DCD‐donors for multiorgan‐HTs has increased rapidly in the United States and early outcomes of DCD heart–kidney transplantations are promising. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory autoimmune neurological disease characterized by the recurrent appearance of demyelinating lesions and progressive disability. Currently, there are multiple disease-modifying treatments, however, there is a significant need to develop new therapeutic targets, especially for the progressive forms of the disease. This review article provides an overview of the most recent studies aimed at understanding the inflammatory processes that are activated in response to the accumulation of kynurenine pathway (KP) metabolites, which exacerbate an imbalance between immune system cells (e.g., Th1, Th2, and T reg) and promote the release of pro-inflammatory interleukins that modulate different mechanisms: membrane-receptors function; nuclear factors expression; and cellular signals. Together, these alterations trigger cell death mechanisms in brain cells and promote neuron loss and axon demyelination. This hypothesis could represent a remarkable approach for disease-modifying therapies for MS. Here, we also provide a perspective on the repositioning of some already approved drugs involved in other signaling pathways, which could represent new therapeutic strategies for MS treatment. [ABSTRACT FROM AUTHOR]

Donor blood transfusion may potentially affect transplant outcomes through an inflammatory response, recipient sensitization, or transmission of infection. The aim of this study was to evaluate the association of donor blood transfusion with outcomes of liver transplantation (LT). From January 2004 to December 2022, donor blood transfusion information was available for 113,017 adult recipients of LT in the United Network for Organ Sharing database and was classified into 4 levels of transfusion: no-transfusion (N = 68,130), transfusion of 1-5 units (N = 33,629), 6-10 units (N = 8067), and >10 units (N = 5329). Recipient survival analysis was performed by Kaplan–Meier method and multivariable Cox-hazard model. Among this cohort, 40.8% of donors (N = 46,261) received blood transfusion during the index hospitalization. Compared to no-blood transfusion donors, blood transfusion donors were younger (median age 37 versus 46 y P < 0.001) and were more brain death donors (94.5% versus 92.1%, P < 0.001). An increased risk of rejection at 6-mo (transfusion 10.3% versus no-transfusion 9.9%, P = 0.055) and 1 y (transfusion 12.5% versus no-transfusion 11.9%, P = 0.0036) post-LT was noted in this cohort. Multivariable Cox-hazard model showed blood transfusion was associated with increased 1-y mortality (transfusion 1.07; 95% CI 1.02-1.12, P = 0.007) and graft failure (transfusion 1.09; 95% CI 1.04-1.13, P < 0.001). Donor blood transfusion was associated with an increased risk of rejection at 6 mo and 1 y among LT recipients and worse post-transplant graft and overall survival. Additional information regarding donor blood transfusion, along with other known factors, may be considered when deciding the optimization of overall immune suppression in LT recipients to decrease the risk of delayed rejection. [ABSTRACT FROM AUTHOR]

Background: Apnea testing is mandatory to confirm brain death; however, it is unsafe for patients who have substantial hypoxemia without ventilator support. We used a new modified apnea test without the need to disconnect the patient from the ventilator in the present study and compared the outcomes and complications of the new method to the widely used old method. Materials and Methods: The current study was conducted on people suspected of having brain death. Both the old and new apnea tests were carried out on the same individual. In the new modified method, instead of hyperventilating and then separating the brain death from the ventilator, the induced hypercapnia method was used, and instead of performing repeated arterial blood gas (ABG), the target ETCO2 was obtained, and at the time of the target ETCO2, ABG was also checked followed by comparing ETCO2 with PaCO2. Results: Thirty patients, including 25 (83.3%) males and 5 (16.75%) females, were included in the study. The results showed significant improvement in terms of O2 saturation and heart rate (HR) using the new modified apnea test compared to the common test. Systolic blood pressure, diastolic blood pressure, and the frequency of complications were improved in the new modified test. Conclusion: The modified apnea test produced better results in terms of O2 saturation, HR, and other clinical factors, while it does not require disconnection from the ventilator and repeated ABG assessment. Therefore, it can be used to successfully diagnose brain death in high-risk individuals suffering from severe hypoxia. [ABSTRACT FROM AUTHOR]

Rituals are central to the everyday life of the nurse, yet the fundamental roles that rituals play in caring for the dead and dying has often been neglected. This paper explores modern palliative and post-mortem care – its practices, practitioners and arenas – against the background of long-held, global concerns regarding the dead and dying. Comparison with the archaeological and ethnographic records demonstrates the ubiquitous and enduring practices surrounding death, and the centrality of ritual specialists to this complex social and biological process. This deep-time perspective highlights the importance of nurses, and their associated nursing rituals, in the transition of patients between life and death, and the difficult journeys that nurse, patient and family undertake in this mediation between worlds. Such a perspective not only empowers nurses in their daily practices, and places nursing rituals firmly at the centre of modern palliative care work, but demonstrates the value of archaeology and ethnography in contextualising the challenges of today. [ABSTRACT FROM AUTHOR]

Background: The global organ shortage is the biggest obstacle to expand urgently needed liver transplantation activities. In addition to donation after brain death (DBD), donation after primary circulatory death (DCD) has also been introduced in many European countries to increase the number of donated organs. Objective: This article summarizes the legal and ethical aspects of DCD, the practical donation process of DCD, the clinical results of DCD liver transplantation with a special focus on organ assessment before a planned DCD liver transplantation. Results: In Europe 11 countries have active DCD liver transplantation programs and a total of 1230 DCD liver transplantations were performed in Europe in 2023. The highest proportion of DCD liver transplantations were recorded in Belgium (52.8%), the Netherlands (42.8%) and Switzerland (32.1%). The adequate selection of donors and recipients is crucial in DCD transplantation and the use of DCD livers particularly depends on the preparedness of the healthcare system for routine machine perfusion. The leaders are Belgium, France and Italy which implant around 68–74% of DCD organs. With an adequate organ assessment, the long-term results of DBD and DCD liver transplantations are comparable. To assess mitochondrial damage and thus organ quality, hypothermic oxygenated machine perfusion (HOPE) was introduced and has the secondary benefit of mitochondrial protection through oxygenation. The establishment of aerobic metabolism in mitochondria under hypothermia leads to a reduction of toxic metabolites and the restoration of ATP storage, which subsequently leads to a reperfusion light during implantation. Conclusion: Expanding the donor pool with DCD donors can counteract the global organ shortage. With adequate patient selection and routine organ assessment short-term and also long-term outcomes of DBD and DCD liver transplantation are comparable. [ABSTRACT FROM AUTHOR]

The incidence of brain death/death by neurologic criteria (BD/DNC) among all hospital deaths in the US is approximately 2.06% or 15,000-20,000 cases annually. This article reviews the latest guidelines for adult and pediatric BD/DNC. Although there have not been many changes to the guidelines over the years, BD/DNC guideline updates maintain consistency in determining BD/DNC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To systematically review the evidence for the effectiveness and safety of magnesium sulfate as a fetal neuroprotective agent when given to individuals at risk of preterm birth. DATA SOURCES: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (through March 17, 2023), and reference lists of relevant studies. METHODS OF STUDY SELECTION: Randomized controlled trials (RCTs) assessing magnesium sulfate for fetal neuroprotection in pregnant participants at risk of imminent preterm birth were eligible. Two authors assessed RCTs for inclusion, extracted data, and evaluated risk of bias, trustworthiness, and evidence certainty (GRADE [Grading of Recommendations Assessment, Development and Evaluation]). TABULATION, INTEGRATION, AND RESULTS: We included six RCTs (5,917 pregnant participants and 6,759 fetuses at less than 34 weeks of gestation at randomization). They were conducted in high-income countries (two in the United States, two across Australia and New Zealand, and one each in Denmark and France) and commenced between 1995 and 2018. Primary outcomes: up to 2 years of corrected age, magnesium sulfate compared with placebo reduced the risk of cerebral palsy (risk ratio [RR] 0.71, 95% CI, 0.57-0.89; six RCTs, 6,107 children) and death or cerebral palsy (RR 0.87, 95% CI, 0.77-0.98; six RCTs, 6,481 children) (high-certainty evidence). Magnesium sulfate had little or no effect on death up to 2 years of corrected age (moderate-certainty evidence) or these outcomes at school age (low-certainty evidence). Although there was little or no effect on death or cardiac or respiratory arrest for pregnant individuals (low-certainty evidence), magnesium sulfate increased adverse effects severe enough to stop treatment (RR 3.21, 95% CI, 1.88-5.48; three RCTs, 4,736 participants; moderate-certainty evidence). Secondary outcome: magnesium sulfate reduced the risk of severe neonatal intraventricular hemorrhage (moderate-certainty evidence). CONCLUSION: Magnesium sulfate for preterm fetal neuroprotection reduces cerebral palsy and death or cerebral palsy for children. Further research is required on longer-term benefits and harms for children, effect variation by participant and treatment characteristics, and the generalizability of findings to low- and middleincome countries. [ABSTRACT FROM AUTHOR]

Family disputes over the diagnosis of brain death have caused much controversy in the bioethics literature over the conceptual validity of the brain death standard. Given the tenuous status of brain death as death, it is pragmatically fruitful to reframe intractable debates about the metaphysical nature of brain death as metalinguistic disputes about its conceptual deployment. This new framework leaves the metaphysical debate open and brings into focus the social functions that are served by deploying the concept of brain death. In doing so, it highlights the epistemic injustice of medicolegal authorities that force people to uniformly accept brain death as a diagnosis of death based on normative considerations of institutional interests, such as saving hospital resources and organ supplies, rather than empirical evidence of brain death as death, which is insufficient at best and nonexistent at worst. In light of this injustice, I propose the rejection of the uniform standard of brain death in favor of a choice-based system that respects families' individualized views of death. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 60-year-old woman with chronic obstructive pulmonary disease and other health issues who presented with confusion, coma, and brainstem areflexia. It states that despite initial concerns of brain death, further investigation revealed no acute brain injury or clear cause for her symptoms, highlighting diagnostic challenges and the potential for false positive drug screenings.

In solid organ transplantation (SOT), biologicals such as recombinant therapeutic proteins, monoclonal antibodies, fusion proteins and conjugates are increasingly used for immunosuppression, desensitization, ABO (blood group) incompatibility, antibody‐mediated rejections and atypical haemolytic uremic syndrome. In this paper, we review the medical evidence available for biologicals used in SOT and the potential for improvement by the application of therapeutic drug monitoring (TDM) and model‐informed precision dosing. Biologicals are used for off‐label indications within the field of SOT, building on the experience from their use on labelled indications. Dosing is currently mostly standard, and experience vs. effect and toxicity is limited. Pharmacokinetic characteristics of these large, partly also immunogenic molecules differ from those of traditional small molecules. Individualization by concentration measurements and modelling has mostly been proof‐of‐concept or feasibility studies that lack the power to provide evidence for improvement in clinical outcome. For some drugs such as alemtuzumab, eculizumab, rituximab, tocilizumab and belatacept, studies have demonstrated significant interindividual variability in pharmacokinetics. Variability in absorption from subcutaneous administration may increase interindividual variability. There is also an economic aspect of appropriate dosing that needs to be pursued. Available assays and models to refine interpretation are in place, but trials of adequate size to document the usefulness of TDM and MIPD are scarce. Collaboration within the TDM community seems mandatory to establish studies of sufficient strength to provide evidence for the use of biologicals that are currently used off‐label in SOT and furthermore to identify the settings where TDM may be beneficial. [ABSTRACT FROM AUTHOR]

Ex situ heart perfusion (ESHP) has emerged as an important strategy to preserve donation after brain death (DBD) and donation after circulatory death (DCD) donor hearts. Clinically, both DBD and DCD hearts are successfully preserved using ESHP. Viability assessment is currently based on biochemical values, while a reliable method for graft function assessment in a physiologic working mode is unavailable. As functional assessment during ESHP has demonstrated the highest predictive value of outcome post-transplantation, this is an important area for improvement. In this study, a novel method for ex situ assessment of left ventricular function with pressure-volume loop analyses is evaluated. Ovine hearts were functionally evaluated during normothermic ESHP with the novel pressure-volume loop system. This system provides an afterload and adjustable preload to the left ventricle. By increasing the preload and measuring end-systolic elastance, the system could successfully assess the left ventricular function. End-systolic elastance at 60 min and 120 min was 2.8 ± 1.8 mmHg/mL and 2.7 ± 0.7 mmHg/ mL, respectively. In this study we show a novel method for functional graft assessment with ex situ pressure-loop analyses during ESHP. When further validated, this method for pressure-volume assessments, could be used for better graft selection in both DBD and DCD donor hearts. [ABSTRACT FROM AUTHOR]

It is well established that sevoflurane exposure leads to widespread neuronal cell death in the developing brain. Adenosine deaminase acting on RNA-1 (ADAR1) dependent adenosine-to-inosine (A-to-I) RNA editing is dynamically regulated throughout brain development. The current investigation is designed to interrogate the contributed role of ADAR1 in developmental sevoflurane neurotoxicity. Herein, we provide evidence to show that developmental sevoflurane priming triggers neuronal pyroptosis, apoptosis and necroptosis (PANoptosis), and elicits the release of inflammatory factors including IL-1β, IL-18, TNF-α and IFN-γ. Additionally, ADAR1-P150, but not ADAR1-P110, depresses cellular PANoptosis and inflammatory response by competing with Z-DNA/RNA binding protein 1 (ZBP1) for binding to Z-RNA in the presence of sevoflurane. Further investigation demonstrates that ADAR1-dependent A-to-I RNA editing mitigates developmental sevoflurane-induced neuronal PANoptosis. To restore RNA editing, we utilize adeno-associated virus (AAV) to deliver engineered circular ADAR-recruiting guide RNAs (cadRNAs) into cells, which is capable of recruiting endogenous adenosine deaminases to promote cellular A-to-I RNA editing. As anticipated, AAV-cadRNAs diminishes sevoflurane-induced cellular Z-RNA production and PANoptosis, which could be abolished by ADAR1-P150 shRNA transfection. Moreover, AAV-cadRNAs delivery ameliorates developmental sevoflurane-induced spatial and emotional cognitive deficits without influence on locomotor activity. Taken together, these results illustrate that ADAR1-P150 exhibits a prominent role in preventing ZBP1-dependent PANoptosis through A-to-I RNA editing in developmental sevoflurane neurotoxicity. Application of engineered cadRNAs to rectify the compromised ADAR1-dependent A-to-I RNA editing provides an inspiring direction for possible clinical preventions and therapeutics. [ABSTRACT FROM AUTHOR]

AbstractMuch of the debate over the definition and criteria for determining our death has focused on disagreement over the correct biological account of death, i.e., what it means for any organism to die. In this paper, we argue that this exclusive focus on the biology of death is misguided, because it ignores ethical and social factors that bear on the acceptability of criteria for determining our death. We propose that attention shift from strictly biological considerations to ethical and social considerations that bear on the determination of what we call “civil death.” We argue for acceptance of a neurological criterion for determining death on grounds that it is the most reasonable way to synthesize biological, ethical, and social considerations about our death.. [ABSTRACT FROM AUTHOR]

Apparently, understanding airway management status may help to reduce risk and improve clinical practice. Given these facts, our team conducted a second survey on the current status of airway management for mainland China following our 2016 national airway survey. The national survey was conducted from November 7 to November 28, 2022. An electronic survey was sent to the New Youth Anesthesia Forum, where Chinese anesthesiologists completed the questionnaire via WeChat. A total of 3783 respondents completed the survey, with a response rate of 72.14%. So far, in 2022, 34.84% of anesthesiologists canceled or delayed surgery at least once due to difficult airway. For the anticipated difficult airway management, 66.11% of physicians would choose awake intubation under sedation and topical anesthesia, while the percentage seeking help has decreased compared to the 2016 survey. When encountering an emergency, 74.20% of respondents prefer to use the needle cricothyrotomy, albeit less than a quarter have actually performed it. Anesthesiologists with difficult airway training experience reached 72.96%, with a significant difference in participation between participants in Tier 3 hospitals and those in other levels of hospitals (P < 0.001). The videolaryngoscope, laryngeal mask, and flexible intubation scope were equipped at 97.18%, 95.96%, and 62.89%, respectively. Additionally, the percentage of brain damage or death caused by difficult airways was significantly decreased. The study may be the best reference for understanding the current status of airway management in China, revealing the current advancements and deficiencies. The future focus of airway management remains on training and education. [ABSTRACT FROM AUTHOR]

AbstractEfforts to revise the Uniform Determination of Death Act in order to align law with medical practice have failed. Medical practice must now align with the law. People who are not dead under the law that defines death should not be declared dead. There is no compelling reason to continue the practice of declaring legally living persons to be dead. [ABSTRACT FROM AUTHOR]

In this article we propose to analyze how healthcare personnel involved in organ and tissue procurement activities use black humor during their daily work. The objective here is twofold: on the one hand, following previous studies, we are interested in showing the role of black humor as a way of dealing with death. On the other hand, we suggest that, in a parallel and complementary way, in this context black humor exposes a performative sense as a form of agency that attempts to modify an adverse reality. This work combines the methodological tools provided by ethnography and conducting open, multi-session interviews. The events revealed during the fieldwork and interviews that associate humor and brain death show the uses, limits and ways in which black humor operates in daily healthcare work of physical and emotional complexity. [ABSTRACT FROM AUTHOR]