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Background: Neurologically critically ill patients present with unique disease trajectories, prognostic uncertainties, and challenges to end-of-life (EOL) care. Acute brain injuries place these patients at risk for underrecognized symptoms and unmet EOL management needs, which can negatively affect their quality of care and lead to complicated grief in surviving loved ones. To care for patients nearing the EOL in the neurointensive care unit, health care clinicians must consider neuroanatomic localization, barriers to symptom assessment and management, unique aspects of the dying process, and EOL management needs. Aim: We aim to define current best practices, barriers, and future directions for EOL care of the neurologically critically ill patient. [ABSTRACT FROM AUTHOR]

We have a reason to value the Uniform Determination of Death Act (UDDA). Since enactment, the UDDA has been of paramount importance to US citizens, families of comatose patients, and the health care professionals who care for them. The UDDA sets forth two standards for determining death and leaves to the medical community to elaborate criteria by which physicians can determine when those standards have been met. Neurologists and neurocritical care experts always have been center stage in this effort. Perfectly established, why change it? What ignited the recent review of the UDDA were lawsuits questioning medical (neurological) authority leading to the wording and accuracy of the UDDA being revisited. The major objections to the language of the UDDA by several groups led a committee appointed by the Uniform Law Commission to consider several substantial changes in the Act. After several years of discussion without reaching a consensus, the committee's chair suspended the effort. Upending the UDDA will lead to a legal crisis and confusion across the states. We present our main arguments against revising this statute and argue that the committee's failure to revise the UDDA should actually be seen as a necessary success. [ABSTRACT FROM AUTHOR]

Background: The Center for Medicare and Medicaid Services requires Organ Procurement Organizations (OPOs) to verify and document that any potential organ donor has been pronounced dead per applicable legal requirements of local, state, and federal laws. However, OPO practices regarding death by neurologic criteria (DNC) verification are not standardized, and little is known about their DNC verification processes. This study aimed to explore OPO practices regarding DNC verification in the United States. Methods: An electronic survey was sent to all 57 OPOs in the United States from June to September 2023 to assess verification of policies and practices versus guidelines, concerns about policies and practices, processes to address concerns about DNC determination, and communication practices. Results: Representatives from 12 OPOs across six US regions completed the entire survey; 8 of 12 reported serving > 50 referral hospitals. Most respondents (11 of 12) reported comparing their referral hospital's DNC policies with the 2010 American Academy of Neurology Practice Parameter and/or other (4 of 12) guidelines. Additionally, most (10 of 12) reported independently reviewing and verifying each DNC determination. Nearly half (5 of 12) reported concerns about guideline-discordant hospital policies, and only 3 of 12 thought all referral hospitals followed the 2010 American Academy of Neurology Practice Parameter in practice. Moreover, 9 of 12 reported concerns about clinician knowledge surrounding DNC determination, and most (10 of 12) reported having received referrals for patients whose DNC declaration was ultimately reversed. All reported experiences in which their OPO requested additional assessments (11 of 12 clinical evaluation, 10 of 12 ancillary testing, 9 of 12 apnea testing) because of concerns about DNC determination validity. Conclusions: Accurate DNC determination is important to maintain public trust. Nearly all OPO respondents reported a process to verify hospital DNC policies and practices with medical society guidelines. Many reported concerns about clinician knowledge surrounding DNC determination and guideline-discordant policies and practices. Educational and regulatory advocacy efforts are needed to facilitate systematic implementation of guideline-concordant practices across the country. [ABSTRACT FROM AUTHOR]

This study explores the role and mechanism of Annexin-A1 Tripeptide (ANXA1sp) in mitigating neuronal damage and promoting functional recovery in a mouse model of traumatic brain injury (TBI). Our goal is to identify ANXA1sp as a potential therapeutic drug candidate for TBI treatment. Adult male C57BL/6J mice were subjected to controlled cortical impact (CCI) to simulate TBI, supplemented by an in vitro model of glutamate-induced TBI in HT22 cells. We assessed neurological deficits using the Modified Neurological Severity Score (mNSS), tested sensorimotor functions with beam balance and rotarod tests, and evaluated cognitive performance via the Morris water maze. Neuronal damage was quantified using Nissl and TUNEL staining, while microglial activation and inflammatory responses were measured through immunostaining, quantitative PCR (qPCR), Western blotting, and ELISA. Additionally, we evaluated cell viability in response to glutamate toxicity using the Cell Counting Kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release. Intraperitoneal administration of ANXA1sp significantly enhanced neurological outcomes, markedly reducing sensorimotor and cognitive impairments caused by TBI. This treatment resulted in a significant reduction in lesion volume and decreased neuronal cell death in the ipsilateral cortex. Moreover, ANXA1sp effectively diminished microglial activation around the brain lesion and decreased the levels of pro-inflammatory markers such as IL-6, IL-1β, TNF-α, and TGF-β in the cortex, indicating a significant reduction in neuroinflammation post-TBI. ANXA1sp also offered protection against neuronal cell death induced by glutamate toxicity, primarily by inhibiting the nuclear translocation of ANXA1, highlighting its potential as a neuroprotective strategy in TBI management. Administration of ANXA1sp significantly reduced neuroinflammation and neuronal cell death, primarily by blocking the nuclear translocation of ANXA1. This treatment substantially reduced brain damage and improved neurological functional recovery after TBI. Consequently, ANXA1sp stands out as a promising neuroprotective agent for TBI therapy. [ABSTRACT FROM AUTHOR]

Delayed graft function (DGF) is an early complication after kidney transplantation. The literature on DGF has experienced substantial growth. However, there is a lack of bibliometric analysis of DGF. This study aimed to analyze the scientific outputs of DGF and explore its hotspots from 2013 to 2023 by using CiteSpace and VOSviewer. The 2058 pieces of literature collected in the Web of Science Core Collection (WOSCC) from 1 January 2013 to 31 December 2023 were visually analyzed in terms of the annual number of publications, authors, countries, journals, literature co-citations, and keyword clustering by using CiteSpace and VOSviewer. We found that the number of papers published in the past ten years showed a trend of first increasing and then decreasing; 2021 was the year with the most posts. The largest number of papers was published by the University of California System, and the largest number of papers was published by the United States. The top five keyword frequency rankings are: 'delayed graft function', 'kidney transplantation', 'renal transplantation', 'survival', and 'recipients'. These emerging trends include 'brain death donors', 'blood absence re-injection injuries', 'tacrolimus', 'older donors and recipients', and 'artificial intelligence and DGF'. In summary, this study reveals the authors and institutions that could be cooperated with and discusses the research hotspots in the past ten years. It provides a reference and direction for future research and application of DGF. [ABSTRACT FROM AUTHOR]

Introduction: The antioxidant effects of vitamins may attenuate the oxidative stress on organs imposed by ischemia–reperfusion injury during the process of organ transplantation from brain-dead donors. Circulating levels of vitamins A, C, and E-α in donors after brain death and their relationships to donor demographics, management, organ utilization, and recipient outcomes are largely unknown. Methods: An observational, prospective, cohort study of 84 consecutive brain-dead organ donors managed at a single organ procurement recovery center was conducted. Vitamin levels were drawn immediately prior to procurement. Results: Levels of serum vitamins A and E-α and plasma vitamin C were below normal in 80%, 85%, and 92% of donors and deficient in 40%, 62%, and 63%, respectively. Vitamin C deficiency was associated with a longer time between death and specimen collection (P =.004). Death from head trauma and stroke were associated with lower levels of vitamin A than from anoxic causes (P =.003) and smokers had greater vitamin C deficiency (P =.03). During donor management, vitamin C deficiency was associated with longer vasopressor support (P =.03) and normal levels of vitamin E-α were associated with reaching a lower alanine transferase compared to those with subnormal levels (P <.05). Donors deficient in vitamin E-α were less likely to have a liver recovered for transplantation (P =.005). Vitamin levels were not associated with the recipient outcomes examined. Conclusion: Circulating vitamins A, C, and E-α is profoundly low in brain-dead organ donors, associated with relevant demographic features of the donor, and may influence donor management and organ utilization. [ABSTRACT FROM AUTHOR]

Although India's organ donation rate is less than 1 per million population, significant disparities exist between the regions and centres within the country, leading to varying consent rates among different organ donation centres. Therefore, this study aimed to understand the experience of transplant coordinators and their barriers and facilitators in the deceased organ donation process across various organ donation centres in India. A phenomenological study using interviews was conducted among fourteen transplant coordinators purposefully recruited from public and private organ donation centres in India, with experience between six years and more than a decade. Audio recordings were transcribed and analysed using framework analysis. Five themes were identified namely: (1) supportive management policies, (2) infrastructure for the deceased organ donation process, (3) delays in the processing time, (4) active involvement in the identification process, and (5) explaining the concept of brain death. The study identifies that implementation priorities include strengthening teamwork, streamlining processes, optimising infrastructure for sensitive discussions, efficient donor identification, and empathetic handling of donor families' grief stages. Collaborating with law enforcement, applying successful medico-legal strategies, improving family communication, and clarifying brain death concepts ethically and legally can boost consent rates, fostering informed decisions and possibly achieving self-sufficiency in deceased organ donation. [ABSTRACT FROM AUTHOR]

Organs obtained from brain dead donors can have suboptimal outcomes. Activation of the innate immune system and translocation of intestinal bacteria could be causative. Thirty two pigs were assigned to control, brain death (BD), BD + luminal intestinal polyethylene glycol (PEG), and BD + luminal intestinal University of Wisconsin solution (UW) groups. Animals were observed for 360 min after BD before organ retrieval. 2,000 mL luminal intestinal preservation solution was instilled into the duodenum at the start of organ procurement. Repeated measurements of plasma C3a, Terminal Complement Complex (TCC), IL-8, TNF, and lipopolysaccharide binding protein were analysed by immunoassays. C3a was significantly higher in the BD groups compared to controls at 480 min after brain death. TCC was significantly higher in BD and BD + UW, but not BD + PEG, compared to controls at 480 min. TNF was significantly higher in the BD group compared to all other groups at 480 min. LPS binding protein increased following BD in all groups except BD + PEG, which at 480 min was significantly lower compared with all other groups. Brain death induced innate immune system activation was decreased by luminal preservation using PEG during organ procurement, possibly due to reduced bacterial translocation. [ABSTRACT FROM AUTHOR]

The main purpose of our research highlights a lack of awareness about donor laws, inadequate implementation, and critical challenges that require legal reform, enhanced support for donors, and better training for healthcare professionals. The legislative framework for organ transplantation varies widely across Asian countries, reflecting differences in cultural, ethical, and legal perspectives. Organ transplantation involves transferring organs, tissues, or cells from donors to recipients, with a significant global demand surpassing the available supply. Biomedical ethics, as outlined by Beauchamp and Childress, and further examined by Veatch and Harris, provide a framework for addressing the moral dilemmas associated with transplantation. In Mongolia, the organ transplantation framework is guided by international standards, though there are gaps in legislation, social welfare, and insurance coverage, which impact the effectiveness of the transplant system. [ABSTRACT FROM AUTHOR]

Ischemic stroke consists of rapid neural death as a consequence of brain vessel obstruction, followed by damage to the neighboring tissue known as ischemic penumbra. The cerebral tissue in the core of the lesions becomes irreversibly damaged, however, the ischemic penumbra is potentially recoverable during the initial phases after the stroke. Therefore, there is real need for emerging therapeutic strategies to reduce ischemic damage and its spread to the penumbral region. For this reason, we tested the effect of Extreme Low Frequency Electromagnetic Stimulation (ELF-EMS) on in vitro primary neuronal and microglial cultures under oxygen-glucose deprivation (OGD) conditions. ELF-EMS under basal non-OGD conditions did not induce any effect in cell survival. However, ELF-EMS significantly reduced neuronal cell death in OGD conditions and reduced ischemic induced Ca2+ overload. Likewise, ELF-EMS modulated microglia activation and OGD-induced microglia cell death. Hence, this study suggests potential benefits in the application of ELF-EMS to limit ischemic irreversible damages under in vitro stroke conditions, encouraging in vivo preclinical validations of ELF-EMS as a potential therapeutic strategy for ischemic stroke. [ABSTRACT FROM AUTHOR]

Copper is an important mineral, and moderate copper is required to maintain physiological processes in nervous system including cerebral ischemia/reperfusion (I/R) injury. Over the past few decades, copper induced cell death, named cuprotosis, has attracted increasing attention. Several lines of evidence have confirmed cuprotosis exerts pivotal role in diverse of pathological processes, such as cancer, neurodegenerative diseases, and I/R injury. Therefore, an in-depth understanding of the interaction mechanism between copper-mediated cell death and I/R injury may reveal the significant alterations about cellular copper-mediated homeostasis in physiological and pathophysiological conditions, as well as therapeutic strategies deciphering copper-induced cell death in cerebral I/R injury. [ABSTRACT FROM AUTHOR]

Background: Osmotic Demyelination Syndrome (ODS) encompasses Central Pontine Myelinolysis and Extrapontine Myelinolysis, both of which are serious neurological conditions linked to the overly rapid correction of hyponatremia. Despite growing evidence, the exact etiology of ODS remains incompletely understood. The present paper describes two case studies, aiming to provide a comprehensive overview of the pathological findings and clinical outcomes associated with ODS. Case presentation: Case #1. A 74-year-old woman was admitted to the emergency department following a head trauma caused by a loss of consciousness. Initial laboratory tests revealed severe hyponatremia (sodium level of 101 mmol/L) and hypokalemia (potassium level of 2.9 mmol/L). The patient underwent corrective therapy with saline and potassium chloride. Despite the correction of electrolyte imbalances, the patient developed a hyperintense lesion in the median portion of the pons on T2-fluid-attenuated inversion recovery (FLAIR) MRI sequence 14 days post-treatment, consistent with ODS. The patient's condition deteriorated, leading to irreversible coma and status epilepticus, culminating in death 32 days after admission. Case #2. An 81-year-old woman with a medical history of hypothyroidism, hypertension, major depression, and stage 3 chronic kidney disease presented with mild gait disturbances. Subsequent testing revealed severe hyponatremia (sodium level of 100 mmol/L). Following an initial clinical improvement due to sodium correction, the patient's condition worsened, with symptoms progressing to confusion, lethargy, and eventually, ODS. Dermatological manifestations, including blistering lesions and facial edema, appeared as the condition advanced. The patient succumbed to irreversible coma 47 days after admission. Conclusion: ODS traditionally carried a poor prognosis, with high mortality rates and diagnoses often made postmortem. However, recent advances in understanding the pathophysiology, along with improvements in diagnostic techniques such as MRI and intensive care treatments, have led to earlier identification, treatment, and recognition of milder forms of the syndrome. Despite these advancements, ODS remains a critical condition with significant risks, particularly following the rapid correction of severe hyponatremia. [ABSTRACT FROM AUTHOR]

Objective: A recent update of the French cohort of uranium miners added seven years of follow-up data. We use these new data to look for new possible radon-related increased risks and refine the estimation of the potential association between cumulative radon exposure and four cancer sites: lung cancer, kidney cancer, brain and central nervous system (CNS) cancer and leukemia (excluding chronic lymphocytic leukemia, which is not radiation-induced). Methods: Several parametric survival models are proposed, fitted and compared under the Bayesian paradigm, to perform new and original exposure-risk analyses. In line with recent UNSCEAR recommendations, we consider time-related effect modifiers and exposure rate as potential effect modifying factors. We use Bayesian model selection criteria to identify radon-related increased hazard rates. Results: Under the assumption of a linear exposure-risk relationship, we found a substantial evidence for a strictly positive effect of cumulative radon exposure on the hazard rate of death by lung cancer among French uranium miners. Given the current available data under the assumptions of a linear or log-linear exposure-risk relationship, it is not possible to conclude in favour of the absence or the existence of a strictly positive effect of chronic exposure to radon on the hazard rate of death by kidney cancer. Regarding death by brain and CNS cancer, there is a substantial evidence for the absence of radon-related effect. Finally, under the assumption of a log-linear exposure-risk relationship, a small positive radon-related effect appears when looking at the risk of death by leukemia (excluding CLL). Conclusion: This study investigates the existence of radon-related increased risk of death by lung cancer, kidney cancer, brain and CNS cancer and leukemia under a Bayesian framework and assumptions of linear and log-linear exposure-risk relationships. If there is no doubt in the interpretation of the results for lung cancer and brain and CNS cancer, the conclusion is less clear-cut in the case of kidney cancer and leukemia (excluding CLL). A future update of the French cohort, increasing the follow-up time for miners, may help to reach a clearer conclusion for these two cancer sites. [ABSTRACT FROM AUTHOR]

Objective To analyze the progress and current status of ethical research in the field of organ donation and transplantation in China by bibliometric analysis. Methods Literature review was conducted from CNKI between January 2000 to December 2023. The number of published articles, the cooperation network of core authors, the cooperation network of publication institutions, the co-occurrence of keywords, the emergent keywords and the clustering of keywords were analyzed by CiteSpace 6.2.6. Results A total of 399 valid articles were obtained. The three peaks in the trend of published articles were affected by current policy events and the development of transplantation technology. From 2000 to 2014, the number of published articles showed an upward trend. At this stage, these studies focused on ethical speculation in the field of organ donation and transplantation. From 2015 to 2023, the number of published articles showed a fluctuating trend. During this stage, these researches highlighted the work system of donation and transplantation and ethical issues in medical practice. Organ donation and ethical review after citizen death became the research frontiers. The co-occurrence knowledge map of authors reflected that the authors mainly served as single nodes, lacking of communication among authors. Twenty-five core authors were identified. Diverse publication institutions were searched including medical departments from colleges and universities, ethics research institutions, organ transplantation departments from hospitals, ethics committees from hospitals and human Organ Procurement Organization (OPO), etc. The First Hospital of Kunming published the largest number of articles. A total of 252 keywords and 13 emergent words were extracted. The keywords with the highest degree of emergency consisted of brain death, organ donation, legislation and ethical review. A total of 14 keyword clusters were generated, including organ transplantation, organ donation, organ donation after citizen’s death, ethics, ethical review and medical staff. Conclusions The cooperation among authors and institutions is insufficient in the field of organ donation and transplantation ethics. Multi-center research and cooperation among authors should be strengthened. Extensive efforts should be made to strengthen the exploration and empirical research of ethical issues based on current work system and medical practice, aiming to provide ethical basis and defense for the reform and practice of organ donation and transplantation. [ABSTRACT FROM AUTHOR]

The article discusses the challenges in defining death, particularly in the context of technological advancements like mechanical ventilators. It highlights the shift towards prioritizing the neurological criterion for determining death over the traditional circulatory and respiratory criteria. The author argues for the neurological criterion as the primary definition of death, drawing on Catholic anthropology and ethical considerations. The article also addresses ethical concerns related to organ transplantation and the need for clarity in defining death to uphold human dignity and trust in medical practices. [Extracted from the article]

The article discusses the importance of pediatric organ donation, highlighting the impact children and adolescents have on saving lives through organ transplantation. A retrospective study conducted in a Portuguese hospital from 2006 to 2021 found that 62 pediatric patients were eligible for organ donation, resulting in 252 solid organs being collected and benefiting 202 recipients. Kidneys were the most frequently donated organs, with a median of four organs donated per child. The study emphasizes the need for further research to better understand the contribution of pediatric organ donation to both adults and children awaiting transplants. [Extracted from the article]

With the growing prevalence of health and illness narratives on digital platforms, research examining the social psychological processes involved in these storytelling environments remains scarce. This paper addresses this research gap by conducting a mixed-methods study of digital storytelling within the UK's healthcare context, focusing on online consumer reviews of the medical memoir, Do no harm: stories of life, death and brain surgery (Marsh, 2014). Utilising computer-assisted text analysis methods of LIWC-22 and the Sketch Engine, linguistic cues for cognitive, affective, social and perceptual processes are identified in a corpus of online consumer reviews. A subsequent qualitative analysis, based on 'narrative modulation' (Huang, 2024, 2020), investigates the role of these processes in constructing and developing storylines across the user reviews. Finally, the study explores how consumer reviews in the form of 'small stories' challenge canonical narratives in the UK's healthcare services. This research advances the field of narrative studies by emphasising the role of social psychological processes (Chung and Pennebaker, 2019) in modulating emerging, evolving and counter narratives in digital storytelling. The findings reveal an instrumental role of social psychological processes, as signalled by linguistic cues, in shaping narrative threads in online user reviews. This study not only develops narrative modulation as a valuable concept for narrative analysis, but also underscores its effectiveness when combined with computer-assisted text analysis tools for in-depth examinations of narrative data. Furthermore, it provides critical insights into digital storytelling in healthcare contexts, promoting knowledge transfer across narrative studies, stylistics, social psychology and medical humanities. [ABSTRACT FROM AUTHOR]

Epithelioid glioblastoma (eGB) is a rare and aggressive brain tumor that primarily affects children and young adults. This article presents a case study of a young adult male with eGB, describing the characteristics of the tumor and the genetic alterations commonly found in eGB. The patient had a poor prognosis and died four months after diagnosis. The article emphasizes the importance of recognizing and studying this rare subtype of glioblastoma to improve patient care and prognosis. Treatment options for eGB include BRAF and MEK inhibitor combination therapy. [Extracted from the article]

Background: In Japan, there has never been a national analysis of pediatric deceased donor liver transplantation (pDDLT) based on donor and recipient factors. We constructed a Japanese nationwide database and assessed outcomes of pDDLT focusing on the pediatric prioritization system introduced in 2018. Methods: We collected data on pDDLTs (<18 years) performed between 1999 and 2021 from the Japan Organ Transplant Network and Japanese Liver Transplantation Society, identified risk factors for graft survival and compared the characteristics and graft survival in pDDLTs conducted before and after the introduction of the pediatric prioritization system. Results: Overall, 112 cases of pDDLT were included, with a 1‐year graft survival rate of 86.6%. Four poor prognostic factors were identified: recipient intensive care unit stay, model for end‐stage liver disease/pediatric end‐stage liver disease score, donor cause of death, and donor total bilirubin. After the introduction of the system, allografts from pediatric donors were more reliably allocated to pediatric recipients and the annual number of pDDLTs increased. The 1‐year graft survival rate improved significantly as did pDDLT conditions indicated by the risk factors. Conclusions: Under the revised allocation system, opportunities for pDDLT increased, resulting in favorable recipient and donor conditions and improved survival. [ABSTRACT FROM AUTHOR]

Introduction: Colloid cysts are rare intracranial tumors that can cause obstructive hydrocephalus, a potentially life-threatening condition. Despite being typically benign, they often present with insidious symptoms, leading to delayed diagnosis and catastrophic outcomes. Case Report: A 29-year-old woman presented with a two-month history of worsening headaches, nausea, and vomiting. Neuroimaging revealed a colloid cyst obstructing the third ventricle, resulting in hydrocephalus. Despite emergency placement of an external ventricular drain, the patient's neurological condition deteriorated rapidly, culminating in brain death. Conclusions: This case highlights the critical importance of the early diagnosis and aggressive management of colloid cyst-induced hydrocephalus. The rapid progression of symptoms and devastating outcomes underscore the need for increased awareness among healthcare providers. Given the high mortality associated with this condition, further research is warranted to identify predictive factors and develop effective treatment strategies. [ABSTRACT FROM AUTHOR]

Optimizing immunologic compatibility in organ transplantation extends beyond the conventional approach of Human Leukocyte Antigen (HLA) antigen matching, which exhibits significant limitations. A broader comprehension of the roles of classical and non-classical HLA genes in transplantation is imperative for enhancing long-term graft survival. High-resolution molecular HLA genotyping, despite its inherent challenges, has emerged as the cornerstone for precise patient-donor compatibility assessment. Leveraging understanding of eplet biology and indirect immune activation, eplet mismatch calculators and the PIRCHE-II algorithm surpass traditional methods in predicting allograft rejection. Understanding minor histocompatibility antigens may also present an opportunity to personalize the compatibility process. While the application of molecular matching in deceased donor organ allocation presents multiple technical, logistical, and conceptual barriers, rendering it premature for mainstream use, several other areas of donor-recipient matching and posttransplant management are ready to incorporate molecular matching. Provision of molecular mismatch scores to physicians during potential organ offer evaluations could potentially amplify long-term outcomes. The implementation of molecular matching in living organ donation and kidney paired exchange programs is similarly viable. This article will explore the current understanding of immunologic matching in transplantation and the potential applications of epitope and non-epitope molecular biology and genetics in clinical transplantation. [ABSTRACT FROM AUTHOR]

Optimizing immunologic compatibility in organ transplantation extends beyond the conventional approach of Human Leukocyte Antigen (HLA) antigen matching, which exhibits significant limitations. A broader comprehension of the roles of classical and non-classical HLA genes in transplantation is imperative for enhancing long-term graft survival. High-resolution molecular HLA genotyping, despite its inherent challenges, has emerged as the cornerstone for precise patient-donor compatibility assessment. Leveraging understanding of eplet biology and indirect immune activation, eplet mismatch calculators and the PIRCHE-II algorithm surpass traditional methods in predicting allograft rejection. Understanding minor histocompatibility antigens may also present an opportunity to personalize the compatibility process. While the application of molecular matching in deceased donor organ allocation presents multiple technical, logistical, and conceptual barriers, rendering it premature for mainstream use, several other areas of donor-recipient matching and posttransplant management are ready to incorporate molecular matching. Provision of molecular mismatch scores to physicians during potential organ offer evaluations could potentially amplify long-term outcomes. The implementation of molecular matching in living organ donation and kidney paired exchange programs is similarly viable. This article will explore the current understanding of immunologic matching in transplantation and the potential applications of epitope and non-epitope molecular biology and genetics in clinical transplantation. [ABSTRACT FROM AUTHOR]

Copper is an important mineral, and moderate copper is required to maintain physiological processes in nervous system including cerebral ischemia/reperfusion (I/R) injury. Over the past few decades, copper induced cell death, named cuprotosis, has attracted increasing attention. Several lines of evidence have confirmed cuprotosis exerts pivotal role in diverse of pathological processes, such as cancer, neurodegenerative diseases, and I/R injury. Therefore, an in-depth understanding of the interaction mechanism between copper-mediated cell death and I/R injury may reveal the significant alterations about cellular copper-mediated homeostasis in physiological and pathophysiological conditions, as well as therapeutic strategies deciphering copper-induced cell death in cerebral I/R injury. [ABSTRACT FROM AUTHOR]

Background: Globally, 64–74 million individuals around the world are estimated to sustain traumatic brain injury every year. Moderate and severe traumatic brain injury can lead to a lifetime physical, cognitive, emotional, and behavioral changes. There were limited studies conducted in Ethiopia regarding to traumatic brain injury mortality. Methods: An institutional based retrospective cohort study was conducted on 429 randomly selected traumatic brain injury patients aged 18 to 64 years who were admitted to East Amhara Comprehensive Specialized Hospitals from January 1, 2016 to December 31, 2021. Kobo toolbox was applied for data collection and exported to Stata version 17 for data processing and analysis. To estimate death free time, a Kaplan Meier failure curve was used. The Cox proportional hazards regression model was used at the 5% level of significance to determine effect of predictor variables on time to death. Result: A total of 429 traumatic brain injury patients aged 18 to 64 years were included with response rate of 91.3% and 145(33.8%) were dead. Open injuries (AHR = 0.25; 95% CI: 0.18–0.36), co-existing injuries (AHR = 0.40; 95% CI: 0.24–0.66), ICU admission (AHR = 0.42; 95% CI: 0.29–0.60), arrival within 4–24 h (AHR = 3.48; 95% CI: 2.01–6.03), arrival after 24 h (AHR = 6.69; 95% CI: 3.49–12.28), subdural hematoma (AHR = 2.72; 95% CI: 1.77–4.19), serum albumin < 3.5 g/dL (AHR = 0.66; 95% CI: 0.49–0.94), moderate (AHR = 0.56; 95% CI: 0.21–0.89), and mild traumatic brain injury (AHR = 0.43; 95% CI: 0.29–0.56) were predictors of traumatic brain injury mortality. Conclusion: The finding of this study showed that the mortality was 1/3rd of the total patients. Open injuries, co-existing injuries, ICU admission, arrival time (4–24 h and > 24 h), subdural hematoma, serum albumin < 3.5 g/dL and severity of traumatic brain injury (mild and moderate) were predictors of traumatic brain mortality. Therefore, working on these factors to reduce the morality of traumatic brain injury patients is very important. [ABSTRACT FROM AUTHOR]

Accurate determination of death is a necessary responsibility of the medical profession. Brain death, or death by neurological criteria (DNC), can be legally declared after the determination of permanent loss of clinical brain function, including the capacity for consciousness, brainstem reflexes, and the ability to breathe spontaneously. Despite longstanding debates over the exact definition of brain death or DNC and how it is determined, most middle‐ and high‐income countries have compatible medical protocols and legal policies for brain death or DNC. This review summarizes the 2023 updated guidelines for brain death or DNC determination, which integrate adult and pediatric diagnostic criteria. We discuss the clinical challenges related to brain death or DNC determination in infants and young children. We emphasize that physicians must follow the standardized and meticulous evaluation processes outlined in these guidelines to reduce diagnostic error and ensure no false positive determinations. An essential component of the brain death or DNC evaluation is appropriate and transparent communication with families. Ongoing efforts to promote consistency and legal uniformity in the declaration of death are needed. What this paper adds: Sociocultural sensitivity and appropriate communication with families during the brain death or death by neurological criteria (DNC) evaluation are needed.A key component of the brain death or DNC evaluation is appropriate and transparent communication with families.Uniform international standards and consistent legal definitions for brain death or DNC declaration remain a necessary objective. [ABSTRACT FROM AUTHOR]

Background Post-transplant anemia is a prevalent yet often overlooked condition that poses significant risks. Current guidelines consider the same treatment recommendations and goals for these patients as for chronic kidney disease patients not on dialysis. Previous reports demonstrated a lack of awareness and suboptimal management, indicating a pressing need for improvement. We therefore wanted to update the information on post-transplant anemia. We aimed to describe the present state of anemia management, goals and adherence to guidelines within a representative sample of the kidney transplant (KTx) population. Methods We designed a retrospective nationwide multicenter study including outpatients from eight KTx hospitals. Nephrologists gathered data from electronic medical records encompassing demographics, comorbidities, KTx characteristics and immunosuppressive therapy, and information pertaining to anemia management (laboratory values, previously prescribed treatments and subsequent adjustments). The European statement on the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines was the reference for definitions, drug prescriptions and targets. Anemia occurring within the initial 6 months post-transplantation was classified as early onset. Results We included 297 patients with post-transplant anemia aged 62.8 years (standard deviation 13.6), 60% of whom were male. They had received a graft from cardiac death or brain death donors (61.6% and 31.1%, respectively) a median of 2.5 years (0.5–8.7) before. Among them 77% (n  = 228) were classified as having late post-transplant anemia, characterized by a higher prevalence of microcytic and iron deficiency anemia. A total of 158 patients were on erythropoietic-stimulating agents (ESAs) treatment, yet surprisingly 110 of them lacked iron supplementation. Notably, 44 patients had an indication for iron supplementation and among them, 30 exhibited absolute iron deficiency. Out of the 158 patients receiving ESAs, only 39 surpassed the limit for the ESA resistance index, indicating poor response. This resistance was more frequent among patients with early post-transplant anemia (26.1% vs 9.2%). We have identified iron profile, early post-transplant anemia and estimated glomerular filtration rate as factors associated with the highest risk of resistance Conclusion We found that hemoglobin targets are individualized upwards in post-transplant anemia. In this setting, iron therapy continues to be underutilized, especially intravenous, and iron deficiency and prior events (blood transfusion or hospital admission) explain most of the hyporesponsiveness to ESA. This highlights missed opportunities for precise prescription targeting and adherence to established guidelines, suggesting a need for improved management strategies in post-transplant anemia patients. [ABSTRACT FROM AUTHOR]

The research aims to : -Define resuscitation and its ruling. -Clarify the components of the brain. -Define death and its signs, according to doctors and jurists. -Determine whether the brain or heart is responsible for death. -Examine the condition of patients under resuscitation devices and their jurisprudential classification. -Explain the meaning of autopsy and corpse, the types of autopsy, the ruling of Sharia on it, and the jurisprudential conditions that must be met during an autopsy. Research Method: Inductive method. No new issue arises in this nation without having a ruling in the Book of Allah Almighty. One of the issues faced by this nation is (brain death and autopsy). The scholars of this nation have exerted efforts to extract rulings regarding this issue, and this research discusses this issue and presents the scholars' rulings on it. Some of the key findings of the researcher: The death of a patient must be confirmed if they experience what is known as (brain death) . -The decision to remove or maintain resuscitation devices on the patient should be left to the experts among doctors. -Scholars agree on the sanctity of the Muslim body, both alive and dead, and that autopsy is permissible when there is a pressing need for it. [ABSTRACT FROM AUTHOR]

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;96:812–818 [ABSTRACT FROM AUTHOR]

Background: The use of livers with significant steatosis is associated with worse transplantation outcomes. Brain death donor liver acceptance is mostly based on subjective surgeon assessment of liver appearance, since steatotic livers acquire a yellowish tone. The aim of this study was to develop a rapid, robust, accurate, and cost‐effective method to assess liver steatosis. Methods: From June 1, 2018, to November 30, 2023, photographs and tru‐cut needle biopsies were taken from adult brain death donor livers at a single university hospital for the study. All the liver photographs were taken by smartphones then color calibrated, segmented, and divided into patches. Color and texture features were then extracted and used as input, and the machine learning method was applied. This is a collaborative project between Vall d'Hebron University Hospital and Barcelona MedTech, Pompeu Fabra University, and is referred to as LiverColor. Results: A total of 192 livers (362 photographs and 7240 patches) were included. When setting a macrosteatosis threshold of 30%, the best results were obtained using the random forest classifier, achieving an AUROC = 0.74, with 85% accuracy. Conclusion: Machine learning coupled with liver texture and color analysis of photographs taken with smartphones provides excellent accuracy for determining liver steatosis. [ABSTRACT FROM AUTHOR]

The journal "GesR: Health Law" published an article with various topics, including the assistance to suicide without punishment and the criminal act of killing upon request. Other topics include the approval activities of the Federal Ministry of Health regarding death and "brain death," as well as various judgments on medical law issues. In addition, new laws in the field of justice and the Capital Investor Model Proceedings Act are presented. The article also contains information on comments and updates in the field of corporate law and tax law. [Extracted from the article]

The Federal Ministry of Health has approved guidelines for determining death and "brain death" that were criticized by Prof. Dr. Ulrich Schroth. It is emphasized that a wish for death requires special scrutiny. The guidelines were revised and approved twice, but considered inadequate. The practice of determining "brain death" is based on unfounded claims, and the Federal Medical Association did not fulfill its legal obligation to provide justification. [Extracted from the article]

Background: The commonest echocardiographic measurement, left ventricular ejection fraction, can not necessarily predict mortality of recipients following heart transplantation potentially due to afterload dependency. Afterload‐independent left ventricular stroke work index (LVSWI) is alternatively recommended by the current guideline; however, pulmonary artery catheters are rarely inserted in organ donors in most jurisdictions. We propose a novel non‐invasive echocardiographic parameter, Pressure‐Strain Product (PSP), as a potential surrogate of catheter‐based LVSWI. This study aimed to investigate if PSP could correlate with catheter‐based LVSWI in an ovine model of brain stem death (BSD) donors. The association between PSP and myocardial mitochondrial function in the post‐transplant hearts was also evaluated. Methods: Thirty‐one female sheep (weight 47 ± 5 kg) were divided into two groups; BSD (n = 15), and sham neurologic injury (n = 16). Echocardiographic parameters including global circumferential strain (GCS) and global radial strain (GRS) and pulmonary artery catheter‐based LVSWI were simultaneously measured at 8‐timepoints during 24‐h observation. PSP was calculated as a product of GCS or GRS, and mean arterial pressure for PSPcirc or PSPrad, respectively. Myocardial mitochondrial function was evaluated following 6‐h observation after heart transplantation. Results: In BSD donor hearts, PSPcirc (n = 96, rho =.547, p <.001) showed the best correlation with LVSWI among other echocardiographic parameters. PSPcirc returned AUC of.825 to distinguish higher values of cardiomyocyte mitochondrial function (cut‐off point; mean value of complex 1,2 O2 Flux) in post‐transplant hearts, which was greater than other echocardiographic parameters. Conclusions: PSPcirc could be used as a surrogate of catheter‐based LVSWI reflecting mitochondrial function. [ABSTRACT FROM AUTHOR]

Brominated flame retardants (BFRs) reduce flammability in a wide range of products including electronics, carpets, and paint, but leach into the environment to result in continuous, population-level exposure. Epidemiology studies have correlated BFR exposure with neurological problems, including alterations in learning and memory. This study investigated the molecular mechanisms mediating BFR-induced cell death in hippocampal cells and clarified the impact of hexabromocyclododecane (HBCD) exposure on gene transcription in the hippocampus, dorsal striatum, and frontal cortex of male mice. Exposure of hippocampus-derived HT-22 cells to various flame retardants, including tetrabromobisphenol-A (current use), HBCD (phasing out), or 2,2',4,4'-tetrabromodiphenyl ether (BDE-47, phased out) resulted in time, concentration, and chemical-dependent cellular and nuclear morphology alterations, alterations in cell cycle and increases in annexin V staining. All 3 BFRs increased p53 and p21 expression; however, inhibition of p53 nuclear translocation using pifthrin-α did not decrease cell death. Transcriptomic analysis upon low (10 nM) and cytotoxic (10 μM) BFR exposure indicated that HBCD and BDE-47 altered genes mediating autophagy-related pathways. Further evaluation showed that BFR exposure increased LC3-II conversion and autophagosome/autolysosome formation, and co-exposure with the autophagy inhibitor 3-methyladenine (3-MA) attenuated cytotoxicity. Transcriptomic assessment of select brain regions from subchronically HBCD-exposed male mice demonstrated alteration of genes mediating vesicular transport, with greater impact on the frontal cortex and dorsal striatum compared with the dorsal and ventral hippocampus. Immunoblot analysis demonstrated no increases in cell death or autophagy markers, but did demonstrate increases in the SNARE binding complex protein SNAP29, specifically in the dorsal hippocampus. These data demonstrate that BFRs can induce chemical-dependent autophagy in neural cells in vitro and provide evidence that BFRs induce region-specific transcriptomic and protein expression in the brain suggestive of changes in vesicular trafficking. [ABSTRACT FROM AUTHOR]

The article presents an interview with Adam Omelianchuk, an assistant professor at Baylor College of Medicine's Center for Medical Ethics and Health Policy. He discusses ethical concerns regarding normothermic regional perfusion (NRP), including legal compliance and liability risks, adherence to the dead donor rule, and the need for adequate disclosure to decision-makers and the public.

Use of donation after circulatory death (DCD) and hepatitis C virus (HCV) positive donors in heart transplantation have increased the donor pool. Given poor waitlist outcomes in the adult congenital heart disease (ACHD) population, we investigated waitlist outcomes associated with willingness to consider DCD and HCV+ offers and post-transplant outcomes following HCV+ and DCD transplantation for these candidates. Using the United Network for Organ Sharing database, we identified adult ACHD candidates and recipients listed or transplanted, respectively, between 01/01/2016 and 09/30/2023 for the HCV analysis and between 12/01/2019 and 09/30/2023 for the DCD analysis. Among candidates, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider HCV+ and DCD offers. Among recipients of HCV+ (vs HCV-) and DCD (vs brain death [DBD]) transplants, we compared perioperative outcomes and post-transplant survival. Of 1,436 ACHD candidates from 01/01/2016 to 09/30/2023, 37.0% were willing to consider HCV+ heart offers. Of 886 ACHD candidates from 12/01/2019 to 09/30/2023, 15.5% were willing to consider DCD offers. On adjusted analysis, willingness to consider HCV+ offers was associated with 84% increased likelihood of transplant, and willingness to consider DCD offers was associated with 56% increased likelihood of transplant. Of 904 transplants between 01/01/2016 and 09/30/2023, 6.4% utilized HCV+ donors, and of 540 transplants between 12/01/2019 and 09/30/2023, 6.9% utilized DCD donors. Recipients of HCV+ (vs HCV-) and DCD (vs DBD) heart transplants had similar likelihood of perioperative outcomes and 1-year survival. ACHD candidates who were willing to consider HCV+ and DCD offers were more likely to be transplanted and had similar post-transplant outcomes compared to recipients of HCV- and DBD organs. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF)-A is an angiogenic and proinflammatory cytokine with profound effects on microvascular permeability and vasodilation. Several processes may induce VEGF-A expression in brain-dead organ donors. However, it remains unclear whether donor VEGF-A is linked to adverse outcomes after heart transplantation. We examined plasma VEGF-A levels from 83 heart transplant donors as well as the clinical data of these donors and their respective recipients operated between 2010 and 2016. The donor plasma was analyzed using Luminex-based Multiplex and confirmed with a single-target ELISA. Based on donor VEGF-A plasma levels, the recipients were divided into 3 equal-sized groups (low VEGF <500 ng/liter, n = 28; moderate VEGF 500–3000 ng/liter, n = 28; and high VEGF >3000 ng/liter, n = 27). Biochemical and clinical parameters of myocardial injury as well as heart transplant and kidney function were followed-up for one year, while rejection episodes, development of cardiac allograft vasculopathy, and mortality were monitored for 5 years. Baseline parameters were comparable between the donor groups, except for age, where median ages of 40, 45, and 50 were observed for low, moderate, and high donor plasma VEGF levels groups, respectively, and therefore donor age was included as a confounding factor. High donor plasma VEGF-A levels were associated with pronounced myocardial injury (TnT and TnI), a higher inotrope score, and a higher incidence of primary graft dysfunction in the recipient after heart transplantation. Furthermore, recipients with allografts from donors with high plasma VEGF-A levels had a longer length of stay in the intensive care unit and the hospital, and an increased likelihood for prolonged renal replacement therapy. Our findings suggest that elevated donor plasma VEGF-A levels were associated with adverse outcomes in heart transplant recipients, particularly in terms of myocardial injury, primary graft dysfunction, and long-term renal complications. Donor VEGF-A may serve as a potential biomarker for predicting these adverse outcomes and identifying extended donor criteria. [ABSTRACT FROM AUTHOR]

Introduction: The use of continuous positive airway pressure has been shown to improve the tolerance of the apnea test, a critical component of brain death evaluation. The ability to deactivate the apnea backup setting has made apnea testing possible using several conventional mechanical ventilators. Our goal was to evaluate the safety and efficacy of apnea testing performed on mechanical ventilation, compared with the oxygen insufflation technique, for the determination of brain death. Methods: This was a retrospective study. In 2016, our institution approved a change in policy to permit apnea testing on conventional mechanical ventilation. We examined the records of consecutive adults who underwent apnea testing as part of the brain death evaluation process between 2016 and 2022. Using an apnea test technique was decided at the discretion of the attending physician. Outcomes were successful apnea test and the occurrence of patient instability during the test. This included oxygen desaturation (SpO2) < 90%, hypotension (mean arterial pressure < 65 mm Hg despite titration of vasopressor), cardiac arrhythmia, pneumothorax, and cardiac arrest. Results: Ninety-two adult patients underwent apnea testing during the study period: 58 (63%) with mechanical ventilation, 32 (35%) with oxygen insufflation, and 2 (2%) lacked documentation of technique. Apnea tests could not be completed successfully in 3 of 92 (3%) patients—two patients undergoing the oxygen insufflation technique (one patient with hypoxemia and one patient with hypotension) and one patient on mechanical ventilation (aborted for hemodynamic instability). Hypoxemia occurred in 4 of 32 (12.5%) patients with oxygen insufflation and in zero patients on mechanical ventilation (p = 0.01). Hypotension occurred during 3 of 58 (5%) tests with mechanical ventilation and 4 of 32 (12.5%) tests with oxygen insufflation (p = 0.24). In multivariate analysis, the use of oxygen insufflation was an independent predictor of patient instability during the apnea test (odds ratio 37.74, 95% confidence interval 2.74–520.14). Conclusions: Apnea testing on conventional mechanical ventilation is feasible and offers several potential advantages over other techniques. [ABSTRACT FROM AUTHOR]

Background: Hypoxemia is the main modifiable factor preventing lungs from being transplanted from organ donors after brain death. One major contributor to impaired oxygenation in patients with brain injury is atelectasis. Apnea testing, an integral component of brain death declaration, promotes atelectasis and can worsen hypoxemia. In this study, we tested whether performing a recruitment maneuver (RM) after apnea testing could mitigate hypoxemia and atelectasis. Methods: During the study period, an RM (positive end-expiratory pressure of 15 cm H2O for 15 s then 30 cm H2O for 30 s) was performed immediately after apnea testing. We measured partial pressure of oxygen, arterial (PaO2) before and after RM. The primary outcomes were oxygenation (PaO2 to fraction of inspired oxygen [FiO2] ratio) and the severity of radiographic atelectasis (proportion of lung without aeration on computed tomography scans after brain death, quantified using an image analysis algorithm) in those who became organ donors. Outcomes in RM patients were compared with control patients undergoing apnea testing without RM in the previous 2 years. Results: Recruitment maneuver was performed in 54 patients after apnea testing, with a median immediate increase in PaO2 of 63 mm Hg (interquartile range 0–109, p = 0.07). Eighteen RM cases resulted in hypotension, but none were life-threatening. Of this cohort, 37 patients became organ donors, compared with 37 donors who had apnea testing without RM. The PaO2:FiO2 ratio was higher in the RM group (355 ± 129 vs. 288 ± 127, p = 0.03), and fewer had hypoxemia (PaO2:FiO2 ratio < 300 mm Hg, 22% vs. 57%; p = 0.04) at the start of donor management. The RM group showed less radiographic atelectasis (median 6% vs. 13%, p = 0.045). Although there was no difference in lungs transplanted (35% vs. 24%, p = 0.44), both better oxygenation and less atelectasis were associated with a higher likelihood of lungs being transplanted. Conclusions: Recruitment maneuver after apnea testing reduces hypoxemia and atelectasis in organ donors after brain death. This effect may translate into more lungs being transplanted. [ABSTRACT FROM AUTHOR]

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Background: Healthcare systems and hospitals encounter numerous challenges in the organ donation process.Objectives: This study aims to elucidate the organizational challenges associated with organ donation.Methods: A qualitative content analysis was conducted from February to September 2023. Purposive sampling and semi-structured interviews were employed with 14 family members and staff involved in the organ donation process in northwestern Iran. Data were analyzed using conventional content analysis based on the approach proposed by Lundman and Granheim.Results: The analysis revealed the overarching theme of "organizational challenges of organ donation," which encompassed five categories and twenty-three codes. The categories identified were "Insufficient Resources", "Insufficient Cultural Development", "Professionals Who Waste Opportunities", "Low Organizational Sensitivity", and "Depreciated Human Resources".Conclusion: Medical and healthcare organizations play a crucial role in the organ donation process; however, they face significant challenges in this area. To facilitate and expedite organ donation, it is essential to allocate more funding, provide appropriate media platforms, enhance training and cultural development, and improve the management of human resources involved in the organ donation process.