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Acute brain injury (ABI) remains one of the leading causes of death and disability world-wide. Its treatment is challenging due to the heterogeneity of the mechanisms involved and the variability among individuals. This systematic review aims at evaluating the impact of anti-histone treatments on outcomes in ABI patients and experimental animals and defining the trend of nucleosome levels in biological samples post injury. We performed a search in Pubmed/Medline and Embase databases for randomized controlled trials and cohort studies involving humans or experimental settings with various causes of ABI. We formulated the search using the PICO method, considering ABI patients or animal models as population (P), comparing pharmacological and non-pharmacological therapy targeting the nucleosome as Intervention (I) to standard of care or no treatment as Control (C). The outcome (O) was mortality or functional outcome in experimental animals and patients affected by ABI undergoing anti-NET treatments. We identified 28 studies from 1246 articles, of which 7 were experimental studies and 21 were human clinical studies. Among these studies, only four assessed the effect of anti-NET therapy on circulating markers. Three of them were preclinical and reported better outcome in the interventional arm compared to the control arm. All the studies observed a significant reduction in circulating NET-derived products. NETosis could be a target for new treatments. Monitoring NET markers in blood and cerebrospinal fluid might predict mortality and long-term outcomes. However, longitudinal studies and randomized controlled trials are warranted to fully evaluate their potential, as current evidence is limited.
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Lesões Encefálicas , Humanos , Lesões Encefálicas/metabolismo , Lesões Encefálicas/sangue , Lesões Encefálicas/terapia , Animais , Armadilhas Extracelulares/metabolismo , Nucleossomos/metabolismo , Biomarcadores/metabolismo , Biomarcadores/sangueRESUMO
BACKGROUND: Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support. METHODS: These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels. RESULTS: We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts. CONCLUSIONS: The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI.
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Consenso , Oxigenação por Membrana Extracorpórea , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/normas , Adulto , Técnica Delphi , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Lesões Encefálicas/terapia , Lesões Encefálicas/fisiopatologiaRESUMO
BACKGROUND: People with acquired brain injury (ABI) may experience concurrent conditions such as, mental health and substance use concerns, that require specialized care. There are services that aim to support people with ABI and these conditions separately; however, little is known about the facilitators and barriers of these services. Therefore, the purpose of this study was to engage stakeholders to investigate the facilitators and barriers of healthcare services for ABI and concurrent issues. METHODS: Semi-structured focus groups were conducted in-person and virtually with people with ABI, caregivers, healthcare professionals, and policy makers during a one-day event in British Columbia, Canada. Manifest content analysis was used with a constructivist perspective to analyze data. RESULTS: 90 participants (including 34 people with ABI) provided insights during 15 simultaneous focus groups. Three categories were identified: (1) complexity of ABI, (2) supports, (3) structure of care. Complexity of ABI outlined the ongoing basic needs after ABI and highlighted the need for public awareness of ABI. Supports outlined healthcare professional and community-based supports. Structure of care described people with ABI needing to meet criteria for support, experiences of navigating through the system and necessity of integrated services. CONCLUSIONS: These findings highlight the facilitators and barriers of healthcare services for ABI and concurrent conditions and provide insights into the changes that may be needed. Doing so can improve the accessibility and quality of ABI healthcare services.
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Lesões Encefálicas , Grupos Focais , Acessibilidade aos Serviços de Saúde , Pesquisa Qualitativa , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Substâncias/terapia , Feminino , Masculino , Colúmbia Britânica , Pessoa de Meia-Idade , Adulto , Lesões Encefálicas/terapia , Transtornos Mentais/terapia , IdosoRESUMO
OBJECTIVES: For critically ill patients with acute severe brain injuries, consciousness may reemerge before behavioral responsiveness. The phenomenon of covert consciousness (i.e., cognitive motor dissociation) may be detected by advanced neurotechnologies such as task-based functional MRI (fMRI) and electroencephalography (EEG) in patients who appear unresponsive on the bedside behavioral examination. In this narrative review, we summarize the state-of-the-science in ICU detection of covert consciousness. Further, we consider the prognostic and therapeutic implications of diagnosing covert consciousness in the ICU, as well as its potential to inform discussions about continuation of life-sustaining therapy for patients with severe brain injuries. DATA SOURCES: We reviewed salient medical literature regarding covert consciousness. STUDY SELECTION: We included clinical studies investigating the diagnostic performance characteristics and prognostic utility of advanced neurotechnologies such as task-based fMRI and EEG. We focus on clinical guidelines, professional society scientific statements, and neuroethical analyses pertaining to the implementation of advanced neurotechnologies in the ICU to detect covert consciousness. DATA EXTRACTION AND DATA SYNTHESIS: We extracted study results, guideline recommendations, and society scientific statement recommendations regarding the diagnostic, prognostic, and therapeutic relevance of covert consciousness to the clinical care of ICU patients with severe brain injuries. CONCLUSIONS: Emerging evidence indicates that covert consciousness is present in approximately 15-20% of ICU patients who appear unresponsive on behavioral examination. Covert consciousness may be detected in patients with traumatic and nontraumatic brain injuries, including patients whose behavioral examination suggests a comatose state. The presence of covert consciousness in the ICU may predict the pace and extent of long-term functional recovery. Professional society guidelines now recommend assessment of covert consciousness using task-based fMRI and EEG. However, the clinical criteria for patient selection for such investigations are uncertain and global access to advanced neurotechnologies is limited.
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Estado de Consciência , Eletroencefalografia , Unidades de Terapia Intensiva , Imageamento por Ressonância Magnética , Humanos , Eletroencefalografia/métodos , Estado de Consciência/fisiologia , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/terapia , Prognóstico , Transtornos da Consciência/diagnóstico , Estado TerminalRESUMO
Neurodevelopmental disorders (NDDs) encompass various conditions stemming from changes during brain development, typically diagnosed early in life. Examples include autism spectrum disorder, intellectual disability, cerebral palsy, seizures, dyslexia, and attention deficit hyperactivity disorder. Many NDDs are linked to perinatal events like infections, oxygen disturbances, or insults in combination. This chapter outlines the causes and effects of perinatal brain injury as they relate to microglia, along with efforts to prevent or treat such damage. We primarily discuss therapies targeting microglia modulation, focusing on those either clinically used or in advanced development, often tested in large animal models such as sheep, non-human primates, and piglets-standard translational models in perinatal medicine. Additionally, it touches on experimental studies showcasing advancements in the field.
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Lesões Encefálicas , Microglia , Transtornos do Neurodesenvolvimento , Microglia/metabolismo , Humanos , Animais , Lesões Encefálicas/terapia , Encéfalo , Modelos Animais de Doenças , Recém-NascidoRESUMO
OBJECTIVES: The purpose of this study was to engage key stakeholders in a health research priority-setting process to identify, prioritize and produce a community-driven list of research questions addressing intersectional issues on mental health and addictions (MHA) in acquired brain injury (ABI). METHODS: A multiphasic health research priority-setting process was co-designed and executed with community-based stakeholders, including researchers, health professionals, clinicians, service providers, representatives from brain injury associations, policy makers and people with lived experience of ABI and MHA, including patients and their family members. Stakeholders' ideas led to the generation of research questions, which were prioritized at a 1-day workshop. RESULTS: Fifty-nine stakeholders participated in the priority-setting activity during the workshop, which resulted in a rank-ordered list of the top 10 questions for research addressing the intersections of ABI and MHA. Questions identified touched on several pressing issues (e.g., opioid crisis, homelessness), encompassed multiple subtypes of ABI (e.g., hypoxic-ischaemic, mild traumatic), and involved different domains (e.g., identification, intervention) of health research. CONCLUSIONS: This community-driven health research priority-setting study identified and prioritized research questions addressing the intersections of ABI and MHA. Researchers and funding agencies should use this list to inform their agendas and address stakeholders' most urgent needs, fostering meaningful improvements to clinical services. PATIENT OR PUBLIC CONTRIBUTION: An 11-person working group comprised of people with lived experience, service providers, researchers, healthcare professionals and other key stakeholders collaboratively developed and informed the scope, design, methodology and interpretation of this study. Over 50 community-based stakeholders contributed to the research priority-setting activity. One co-author is a person with lived experience.
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Lesões Encefálicas , Participação dos Interessados , Humanos , Lesões Encefálicas/terapia , Transtornos Relacionados ao Uso de Substâncias/terapia , Saúde Mental , Prioridades em SaúdeRESUMO
INTRODUCTION: Early mobilization benefits critically ill patients, but concerns persist, especially in neurologic intensive care unit patients with acute brain injuries. This study assesses early mobility's impact on cerebrovascular autoregulation (CA) and systemic hemodynamics. METHODS: This single-center retrospective study focused on adult neurologic intensive care unit patients undergoing passive cycle ergometry. Data were collected from December 2020 to April 2022. Physical therapists conducted sessions using a standardized protocol, monitoring mean arterial blood pressure (MAP) and intracranial pressure (ICP). The Pressure Reactivity Index (PRx) was calculated as a measure of CA. Statistical analysis included mixed models and repeated measures ANOVA. RESULTS: Eleven patients undergoing continuous physiologic monitoring and early mobility were included, primarily with subarachnoid hemorrhage or intracranial hemorrhage. Median time to protocol initiation was 4 days, with two patients discontinuing due to hemodynamic disturbances. Over a total of 11-hours of neuromonitoring data, passive cycling demonstrated a significant reduction in heart rate (HR), MAP, and ICP across different rotations per minute (RPM) settings compared to baseline. No significant alterations in PRx or cerebral perfusion pressure (CPP) were noted at various RPM levels. However, a significant difference in PRx emerged between patients who completed the protocol and those who did not, particularly at 10 RPM. DISCUSSION: This study offers preliminary insights into the impact of early mobility on CA in acute brain injured patients. While passive cycling demonstrates promise in preserving cerebral hemodynamics, its tolerability may not be uniform across all brain-injured patients. These findings highlight the need to determine optimal early mobilization timing and intensity in this population, emphasizing the necessity for larger prospective studies to validate these findings and inform clinical practice. DETAILS: This manuscript complies with all instructions to the authors. All coauthors meet the authorship requirements and have reviewed and approved the contents of the manuscript. The manuscript has not been published totally or partly, accepted for publication, or under editorial review for publication elsewhere. We have no conflicts of interest to disclose. STROBE checklist was reviewed prior to the submission of this paper. The manuscript adheres to ethical guidelines and was approved by Cleveland Clinic's institutional research board for retrospective study. There is no funding to disclose for this study.
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Lesões Encefálicas , Circulação Cerebrovascular , Humanos , Projetos Piloto , Masculino , Feminino , Pessoa de Meia-Idade , Circulação Cerebrovascular/fisiologia , Estudos Retrospectivos , Adulto , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/terapia , Idoso , Pressão Intracraniana/fisiologia , Deambulação Precoce/métodos , Homeostase/fisiologia , Hemodinâmica/fisiologia , Monitorização Fisiológica/métodosRESUMO
Brain injury caused by stroke has a high rate of mortality and remains a major medical challenge worldwide. In recent years, there has been significant attention given to the use of human Umbilical cord-derived Mesenchymal Stem Cells (hUC-MSCs) for the treatment of stroke in different adult and neonate animal models of stroke. However, using hUC-MSCs by systemic administration to treat ischemic stroke has not been investigated sufficiently. In this study, we conducted various experiments to explore the neuroprotection of hUC-MSCs in rats. Our findings demonstrate that an intravenous injection of a high dose of hUC-MSCs at 2 × 10^7 cells/kg markedly ameliorated brain injury resulting from ischemic stroke. This improvement was observed one day after inducing transient middle cerebral artery occlusion (MCAO) and subsequent reperfusion in rats. Notably, the efficacy of this single administration of hUC-MSCs surpassed that of edaravone, even when the latter was used continuously over three days. Mechanistically, secretory factors derived from hUC-MSCs, such as HGF, BDNF, and TNFR1, ameliorated the levels of MDA and T-SOD to regulate oxidative stress. In particular, TNFR1 also improved the expression of NQO-1 and HO-1, important proteins associated with oxidative stress. More importantly, TNFR1 played a significant role in reducing inflammation by modulating IL-6 levels in the blood. Furthermore, TNFR1 was observed to influence the permeability of the blood-brain barrier (BBB) as demonstrated in the evan's blue experiment and protein expression of ZO-1. This study represented a breakthrough in traditional methods and provided a novel strategy for clinical medication and trials.
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AVC Isquêmico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Estresse Oxidativo , Ratos Sprague-Dawley , Cordão Umbilical , Animais , Estresse Oxidativo/fisiologia , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical/citologia , Masculino , AVC Isquêmico/metabolismo , AVC Isquêmico/terapia , Ratos , Inflamação/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas/terapia , Neuroproteção/fisiologia , Infarto da Artéria Cerebral Média/terapia , Infarto da Artéria Cerebral Média/metabolismoRESUMO
INTRODUCTION: Therapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and assess the effect of a multi-session transcranial alternating current stimulation (tACS) intervention in subacute brain-injured patients on recovery of consciousness, related brain oscillations and brain network dynamics. METHODS AND ANALYSES: The study is comprised of two phases: a validation phase (n=12) and a randomised controlled trial (n=138). Both phases will be conducted in medically stable brain-injured adult patients (traumatic brain injury and hypoxic-ischaemic encephalopathy), with a Glasgow Coma Scale score ≤12 after continuous sedation withdrawal. Recruitment will occur at the intensive care unit of a Level 1 Trauma Centre in Montreal, Quebec, Canada. The intervention includes a 20 min 10 Hz tACS at 1 mA intensity or a sham session over parieto-occipital cortical sites, repeated over five consecutive days. The current's frequency targets alpha brain oscillations (8-13 Hz), known to be associated with consciousness. Resting-state electroencephalogram (EEG) will be recorded four times daily for five consecutive days: pre and post-intervention, at 60 and 120 min post-tACS. Two additional recordings will be included: 24 hours and 1-week post-protocol. Multimodal measures (blood samples, pupillometry, behavioural consciousness assessments (Coma Recovery Scale-revised), actigraphy measures) will be acquired from baseline up to 1 week after the stimulation. EEG signal analysis will focus on the alpha bandwidth (8-13 Hz) using spectral and functional network analyses. Phone assessments at 3, 6 and 12 months post-tACS, will measure long-term functional recovery, quality of life and caregivers' burden. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Research Ethics Board of the CIUSSS du Nord-de-l'Île-de-Montréal (Project ID 2021-2279). The findings of this two-phase study will be submitted for publication in a peer-reviewed academic journal and submitted for presentation at conferences. The trial's results will be published on a public trial registry database (ClinicalTrials.gov). TRIAL REGISTRATION NUMBER: NCT05833568.
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Transtornos da Consciência , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Transtornos da Consciência/terapia , Transtornos da Consciência/fisiopatologia , Transtornos da Consciência/etiologia , Eletroencefalografia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Cuidados Críticos/métodos , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Encéfalo/fisiopatologia , Lesões Encefálicas/terapia , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/complicações , Escala de Coma de Glasgow , Masculino , Feminino , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/fisiopatologia , Estado de ConsciênciaRESUMO
Neonatal hypoxic-ischemic (HI) brain injury is a prominent cause of neurological morbidity, urging the development of novel therapies. Interventions with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) and mesenchymal stem cells (MSCs) provide neuroprotection and neuroregeneration in neonatal HI animal models. While lysophosphatidylcholine (LPC)-bound n-3 LCPUFAs enhance brain incorporation, their effect on HI brain injury remains unstudied. This study investigates the efficacy of oral LPC-n-3 LCPUFAs from Lysoveta following neonatal HI in mice and explores potential additive effects in combination with MSC therapy. HI was induced in 9-day-old C57BL/6 mice and Lysoveta was orally supplemented for 7 subsequent days, with or without intranasal MSCs at 3 days post-HI. At 21-28 days post-HI, functional outcome was determined using cylinder rearing, novel object recognition, and open field tasks, followed by the assessment of gray (MAP2) and white (MBP) matter injury. Oral Lysoveta diminished gray and white matter injury but did not ameliorate functional deficits following HI. Lysoveta did not further enhance the therapeutic potential of MSC therapy. In vitro, Lysoveta protected SH-SY5Y neurons against oxidative stress. In conclusion, short-term oral administration of Lysoveta LPC-n-3 LCPUFAs provides neuroprotection against neonatal HI by mitigating oxidative stress injury but does not augment the efficacy of MSC therapy.
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Animais Recém-Nascidos , Ácidos Graxos Ômega-3 , Hipóxia-Isquemia Encefálica , Lisofosfatidilcolinas , Transplante de Células-Tronco Mesenquimais , Camundongos Endogâmicos C57BL , Animais , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/administração & dosagem , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/prevenção & controle , Camundongos , Transplante de Células-Tronco Mesenquimais/métodos , Modelos Animais de Doenças , Suplementos Nutricionais , Lesões Encefálicas/prevenção & controle , Lesões Encefálicas/terapia , Fármacos Neuroprotetores/farmacologia , Células-Tronco Mesenquimais , Masculino , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Proteína Básica da MielinaRESUMO
Lung and brain injury that occurs during the perinatal period leads to lifelong disability and is often driven and/or exacerbated by inflammation. Human amniotic epithelial cells (hAEC), which demonstrate immunomodulatory, anti-fibrotic, and regenerative capabilities, are being explored as a therapeutic candidate for perinatal injury. However, limitations regarding scalable manufacturing, storage, transport, and dose-related toxicity have impeded clinical translation. Isolated therapeutic extracellular vesicles (EVs) from stem and stem-like cells are thought to be key paracrine mediators of therapeutic efficacy. The unique characteristics of EVs suggest that they potentially circumvent the limitations of traditional cell-based therapies. However, given the novelty of EVs as a therapeutic, recommendations around ideal methods of production, isolation, storage, and delivery have not yet been created by regulatory agencies. In this concise review, we discuss the pertinence and limitations of cell-based therapeutics in perinatal medicine. We also review the preclinical evidence supporting the use of therapeutic EVs for perinatal therapy. Further, we summarize the arising considerations regarding adequate cell source, biodistribution, isolation and storage methods, and regulatory roadblocks for the development of therapeutic EVs.
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Âmnio , Células Epiteliais , Vesículas Extracelulares , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/transplante , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Âmnio/citologia , Lesões Encefálicas/terapia , Lesão Pulmonar/terapia , Animais , FemininoRESUMO
BACKGROUND: The ability to self-advocate or have a say in one's care is integral to personalised care after acquired brain injury (ABI). This study aimed to understand what constitutes self-advocacy and associated barriers and facilitators throughout hospital transitions and into the community. METHOD: Qualitative methodology was employed with semistructured interviews conducted with 12 people with ABI and 13 family members. Interviews were conducted at predischarge (in-person or via telephone) and 4 months postdischarge (via telephone) from the brain injury rehabilitation unit of a tertiary hospital. Data were thematically analysed using a hybrid deductive-inductive approach. RESULTS: Self-advocacy reflects the process of reclaiming agency or people's efforts to exert influence over care decisions after ABI. Agency varies along a continuum, often beginning with impaired processing of the self or environment (loss of agency) before individuals start to understand and question their care (emerging agency) and ultimately plan and direct their ongoing and future care (striving for agency). This process may vary across individuals and contexts. Barriers to self-advocacy for individuals with ABI include neurocognitive deficits that limit capacity and desire for control over decisions, unfamiliar and highly structured environments and lack of family support. Facilitators include neurocognitive recovery, growing desire to self-advocate and scaffolded support from family and clinicians. CONCLUSION: Self-advocacy after ABI entails a process of reclaiming agency whereby individuals seek to understand, question and direct their ongoing care. This is facilitated by neurocognitive recovery, growing capacity and desire and scaffolded supports. Research evaluating approaches for embedding self-advocacy skills early in brain injury rehabilitation is recommended. PATIENT OR PUBLIC CONTRIBUTION: Two caregivers with lived experience of supporting a family member with ABI were involved in the design and conduct of this study and contributed to and provided feedback on the manuscript.
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Lesões Encefálicas , Tomada de Decisões , Família , Entrevistas como Assunto , Pesquisa Qualitativa , Humanos , Masculino , Feminino , Lesões Encefálicas/terapia , Lesões Encefálicas/reabilitação , Lesões Encefálicas/psicologia , Família/psicologia , Pessoa de Meia-Idade , Adulto , Idoso , Defesa do PacienteRESUMO
OBJECTIVE: This article synthesizes the current literature on prognostication in neurocritical care, identifies existing challenges, and proposes future research directions to reduce variability and enhance scientific and patient-centered approaches to neuroprognostication. LATEST DEVELOPMENTS: Patients with severe acute brain injury often lack the capacity to make their own medical decisions, leaving surrogate decision makers responsible for life-or-death choices. These decisions heavily rely on clinicians' prognostication, which is still considered an art because of the previous lack of specific guidelines. Consequently, there is significant variability in neuroprognostication practices. This article examines various aspects of neuroprognostication. It explores the cognitive approach to prognostication, highlights the use of statistical modeling such as Bayesian models and machine learning, emphasizes the importance of clinician-family communication during prognostic disclosures, and proposes shared decision making for more patient-centered care. ESSENTIAL POINTS: This article identifies ongoing challenges in the field and emphasizes the need for future research to ameliorate variability in neuroprognostication. By focusing on scientific methodologies and patient-centered approaches, this research aims to provide guidance and tools that may enhance neuroprognostication in neurocritical care.
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Cuidados Críticos , Humanos , Cuidados Críticos/métodos , Cuidados Críticos/normas , Prognóstico , Lesões Encefálicas/terapia , Lesões Encefálicas/diagnóstico , Assistência Centrada no PacienteRESUMO
The prevalence of central nervous system (CNS) dysfunction as a result of disease or trauma remains a clinically unsolved problem which is raising increased awareness in our aging society. Human Dental Pulp Stem Cells (hDPSCs) are excellent candidates to be used in tissue engineering and regenerative therapies of the CNS due to their neural differentiation ability and lack of tumorigenicity. Accordingly, they have been successfully used in animal models of spinal cord injury, stroke and peripheral neuropathies. The ideal therapy in brain injury should combine strategies aiming to protect the damaged lesion and, at the same time, accelerate brain tissue regeneration, thus promoting fast recovery while minimizing side or long-term effects. The use of bioresorbable nanopatterned poly(lactide-co-É-caprolactone) (PLCL) polymeric scaffolds as hDPCSs carriers can represent an advantage for tissue regeneration. In this chapter, we describe the surgical procedures to implant functionalized bioresorbable scaffolds loaded with hDPSCs to improve the brain lesion microenvironment in an intracranial stab wound injury model severing the rostral migratory stream (RMS) that connects the brain subventricular zone (SVZ) and the olfactory bulb in nude mice. Additionally, we also describe the technical steps after animal sacrifice for histological tissue observation and characterization.
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Polpa Dentária , Modelos Animais de Doenças , Camundongos Nus , Células-Tronco , Alicerces Teciduais , Polpa Dentária/citologia , Animais , Humanos , Alicerces Teciduais/química , Camundongos , Células-Tronco/citologia , Transplante de Células-Tronco/métodos , Ferimentos Perfurantes/terapia , Implantes Absorvíveis , Lesões Encefálicas/terapia , Lesões Encefálicas/patologia , Engenharia Tecidual/métodosRESUMO
Neonatal neurocritical care (NNCC) has emerged as an important specialty to address neurological conditions affecting newborns including a wide spectrum of brain injuries and developmental impairment. Despite the discipline's growth, variability in NNCC service delivery, patient care, and clinical training poses significant challenges and potentially adversely impacts patient outcomes. Variations in neuroprotective strategies, postnatal care, and training methodologies highlight the urgent need for a unified approach to optimize both short- and long-term neurodevelopmental outcomes for these vulnerable population. This paper presents strategic blueprints for establishing standardized NNCC clinical care and training programs focusing on collaborative effort across medical and allied health professions. By addressing these inconsistencies, the paper proposes that standardizing NNCC practices can significantly enhance the quality of care, streamline healthcare resource utilization, and improve neurodevelopmental outcome, thus paving the way for a new era of neonatal neurological care.
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Cuidados Críticos , Neonatologia , Humanos , Recém-Nascido , Neonatologia/educação , Neonatologia/normas , Cuidados Críticos/normas , Lesões Encefálicas/terapia , Terapia Intensiva Neonatal/normas , Neurologia/educação , Neurologia/normas , Transtornos do Neurodesenvolvimento/terapia , Transtornos do Neurodesenvolvimento/prevenção & controleRESUMO
This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.
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Reanimação Cardiopulmonar , Parada Cardíaca , Humanos , Lesões Encefálicas/etiologia , Lesões Encefálicas/terapia , Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/normas , Parada Cardíaca/complicações , Parada Cardíaca/terapiaRESUMO
In this review, we explore race-based disparities in neonatology and their impact on brain injury and neurodevelopmental outcomes. We discuss the historical context of healthcare discrimination, focusing on the post-Civil War era and the segregation of healthcare facilities. We highlight the increasing disparity in infant mortality rates between Black and White infants, with premature birth being a major contributing factor, and emphasize the role of prenatal factors such as metabolic syndrome and toxic stress in affecting neonatal health. Furthermore, we examine the geographic and historical aspects of racial disparities, including the consequences of redlining and limited access to healthcare facilities or nutritious food options in Black communities. Finally, we delve into the higher incidence of brain injuries in Black neonates, as well as disparities in adverse neurodevelopmental outcome. This evidence underscores the need for comprehensive efforts to address systemic racism and provide equitable access to healthcare resources.