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Objectives: To determine if ChatGPT can incorporate patient-specific information to provide high-quality answers to parental questions in the PICU. We hypothesized that ChatGPT would generate high-quality, patient-specific responses., Methods: In this cross-sectional study, we generated assessments and plans for 3 PICU patients with respiratory failure, septic shock, and status epilepticus and paired them with 8 typical parental questions. We prompted ChatGPT with instructions, an assessment and plan, and 1 question. Six PICU physicians evaluated the responses for accuracy (1-6), completeness (yes/no), empathy (1-6), and understandability (Patient Education Materials Assessment Tool, PEMAT, 0% to 100%; Flesch-Kincaid grade level). We compared answer quality among scenarios and question types using the Kruskal-Wallis and Fischer's exact tests. We used percent agreement, Cohen's Kappa, and Gwet's agreement coefficient to estimate inter-rater reliability., Results: All answers incorporated patient details, utilizing them for reasoning in 59% of sentences. Responses had high accuracy (median 5.0, [interquartile range (IQR), 4.0-6.0]), empathy (median 5.0, [IQR, 5.0-6.0]), completeness (97% of all questions), and understandability (PEMAT % median 100, [IQR, 87.5-100]; Flesch-Kincaid level 8.7). Only 4/144 reviewer scores were <4/6 in accuracy, and no response was deemed likely to cause harm. There was no difference in accuracy, completeness, empathy, or understandability among scenarios or question types. We found fair, substantial, and almost perfect agreement among reviewers for accuracy, empathy, and understandability, respectively., Conclusions: ChatGPT used patient-specific information to provide high-quality answers to parental questions in PICU clinical scenarios., (Copyright © 2024 by the American Academy of Pediatrics.)

Objectives: To describe the doses of opioids and benzodiazepines administered around the time of terminal extubation (TE) to children who died within 1 hour of TE and to identify their association with the time to death (TTD)., Design: Secondary analysis of data collected for the Death One Hour After Terminal Extubation study., Setting: Nine U.S. hospitals., Patients: Six hundred eighty patients between 0 and 21 years who died within 1 hour after TE (2010-2021)., Measurements and Main Results: Medications included total doses of opioids and benzodiazepines 24 hours before and 1 hour after TE. Correlations between drug doses and TTD in minutes were calculated, and multivariable linear regression performed to determine their association with TTD after adjusting for age, sex, last recorded oxygen saturation/F io2 ratio and Glasgow Coma Scale score, inotrope requirement in the last 24 hours, and use of muscle relaxants within 1 hour of TE. Median age of the study population was 2.1 years (interquartile range [IQR], 0.4-11.0 yr). The median TTD was 15 minutes (IQR, 8-23 min). Forty percent patients (278/680) received either opioids or benzodiazepines within 1 hour after TE, with the largest proportion receiving opioids only (23%, 159/680). Among patients who received medications, the median IV morphine equivalent within 1 hour after TE was 0.75 mg/kg/hr (IQR, 0.3-1.8 mg/kg/hr) ( n = 263), and median lorazepam equivalent was 0.22 mg/kg/hr (IQR, 0.11-0.44 mg/kg/hr) ( n = 118). The median morphine equivalent and lorazepam equivalent rates after TE were 7.5-fold and 22-fold greater than the median pre-extubation rates, respectively. No significant direct correlation was observed between either opioid or benzodiazepine doses before or after TE and TTD. After adjusting for confounding variables, regression analysis also failed to show any association between drug dose and TTD., Conclusions: Children after TE are often prescribed opioids and benzodiazepines. For patients dying within 1 hour of TE, TTD is not associated with the dose of medication administered as part of comfort care., Competing Interests: Dr. Winter’s institution received funding from the L.K. Whittier Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

In the five decades since its inception, brain death has become an accepted medical and legal concept throughout most of the world. There was initial reluctance to apply brain death criteria to children as they are believed more likely to regain neurologic function following injury. In spite of early trepidation, criteria for pediatric brain death certification were first proposed in 1987 by a multidisciplinary committee comprised of experts in the medical and legal communities. Protocols have since been developed to standardize brain death determination, but there remains substantial variability in practice throughout the world. In addition, brain death remains a topic of considerable ethical, philosophical, and legal controversy, and is often misrepresented in the media. In the present article, we discuss the history of brain death and the guidelines for its determination. We provide an overview of past and present challenges to its concept and diagnosis from biophilosophical, ethical and legal perspectives, and highlight differences between adult and pediatric brain death determination. We conclude by anticipating future directions for brain death as related to the emergence of new technologies. It is our position that providers should endorse the criteria for brain death diagnosis in children as proposed by the Society of Critical Care Medicine (SCCM), American Academy of Pediatrics (AAP), and Child Neurology Society (CNS), in order to prevent controversy and subjectivity surrounding what constitutes life versus death., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-20-350). The series “Pediatric Critical Care” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Landau-Kleffner syndrome (LKS) has been demonstrated in the past to respond to immunotherapy. Recently, some cases of LKS have been shown to be secondary to glutamate receptor (GRIN2A) mutations. Whether such cases respond to immunotherapy is not known. Here, we present the case of a 3-year-old boy with LKS found to have a GRIN2A heterozygous missense mutation, whose clinical symptoms and EEG responded to a course of combination oral steroids and monthly infusions of intravenous immunoglobulin. He then relapsed after discontinuation of this therapy, and responded again after a second course of intravenous immunoglobulin. We conclude that immunotherapy should be considered as a therapeutic option in patients with LKS who are also found to harbour GRIN2A mutations.

The transforming growth factor-β (TGF-β) signaling pathway serves critical functions in CNS development, but, apart from its proposed neuroprotective actions, its physiological role in the adult brain is unclear. We observed a prominent activation of TGF-β signaling in the adult dentate gyrus and expression of downstream Smad proteins in this neurogenic zone. Consistent with a function of TGF-β signaling in adult neurogenesis, genetic deletion of the TGF-β receptor ALK5 reduced the number, migration and dendritic arborization of newborn neurons. Conversely, constitutive activation of neuronal ALK5 in forebrain caused a marked increase in these aspects of neurogenesis and was associated with higher expression of c-Fos in newborn neurons and with stronger memory function. Our findings describe an unexpected role for ALK5-dependent TGF-β signaling as a regulator of the late stages of adult hippocampal neurogenesis, which may have implications for changes in neurogenesis during aging and disease.

Colony-stimulating factor 1 (CSF1) and interleukin-34 (IL-34) are functional ligands of the CSF1 receptor (CSF1R) and thus are key regulators of the monocyte/macrophage lineage. We discovered that systemic administration of human recombinant CSF1 ameliorates memory deficits in a transgenic mouse model of Alzheimer's disease. CSF1 and IL-34 strongly reduced excitotoxin-induced neuronal cell loss and gliosis in wild-type mice when administered systemically before or up to 6 h after injury. These effects were accompanied by maintenance of cAMP responsive element-binding protein (CREB) signaling in neurons rather than in microglia. Using lineage-tracing experiments, we discovered that a small number of neurons in the hippocampus and cortex express CSF1R under physiological conditions and that kainic acid-induced excitotoxic injury results in a profound increase in neuronal receptor expression. Selective deletion of CSF1R in forebrain neurons in mice exacerbated excitotoxin-induced death and neurodegeneration. We conclude that CSF1 and IL-34 provide powerful neuroprotective and survival signals in brain injury and neurodegeneration involving CSF1R expression on neurons.

In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions. Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise. Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines--including CCL11 (also known as eotaxin)--the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors.