Loss of Katnal2 leads to ependymal ciliary hyperfunction and autism-related phenotypes in mice.

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early postnatal Katnal2 re-expression prevents ciliary, ventricular, and behavioral phenotypes in Katnal2-KO adults, suggesting a causal relationship and a potential treatment. Therefore, Katnal2 negatively regulates ependymal ciliary function and its deletion in mice leads to ependymal ciliary hyperfunction and hydrocephalus accompanying ASD-related behavioral, synaptic, and transcriptomic changes.

Physician Management and CT Ordering in the Emergency Department for Primary Headaches.

OBJECTIVE: Management of primary headache (PHA) varies across emergency departments (ED), yet there is widespread agreement that computed tomography (CT) scans are overused. This study assessed emergency physicians' (EPs) PHA management and their attitudes towards head CT ordering. METHODS: A cross-sectional study was undertaken with EPs from one Canadian center. Drivers of physicians' perceptions regarding the appropriateness of CT ordering for patients with PHA were explored. RESULTS: A total of 73 EPs (70% males; 48% with <10 years of practice) participated in the study. Most EPs (88%) did not order investigations for moderate-severe primary headaches; however, CT was the common investigation (47%) for headaches that did not improve. Computed tomography ordering was frequently motivated by the need for specialist consultation (64%) or admission (64%). A small proportion (27%) believed patients usually/frequently expected a scan. Nearly half of EPs (48%) identified patient imaging expectations/requests as a barrier to reducing CT ordering. Emergency physicians with CCFP (EM) certification were less likely to perceive CT ordering for patients with PHA as appropriate. Conversely, those who identified the possibility of missing a condition as a major barrier to limiting their CT use were more likely to perceive CT ordering for patients with PHA as appropriate. CONCLUSIONS: Emergency physicians reported consistency and evidence-based medical management. They highlighted the complexities of limiting CT ordering and both their level of training and their perceived barriers for limiting CT ordering seem to be influencing their attitudes. Further studies could elucidate these and other factors influencing their practice.

Role of sex and gender in concussion outcome differences among patients presenting to the emergency department: a systematic review.

OBJECTIVE: This systematic review aimed to identify research involving adults presenting to the emergency department (ED) with a concussion to document the reporting of sex and/or gender according to the Canadian Institutes of Health Research (CIHR) guidelines, the prevalence of sex and gender-based analysis (SGBA) and to summarise sex and/or gender-based differences in ED presentation, management and outcomes. DESIGN: Systematic review. METHODS: Electronic databases and grey literature were searched to identify studies that recruited adult patients with concussion from the ED. Two independent reviewers identified eligible studies, assessed quality and extracted data. A descriptive summary of the evidence was generated, and sex and/or gender reporting was examined for accuracy according to standardised criteria. RESULTS: Overall, 126 studies were included in the analyses. A total of 80 (64%) studies reported sex and/or gender as demographic information, of which 51 (64%) included sex and/or gender in their analysis; however, 2 (3%) studies focused on an SGBA. Sex was more accurately reported in alignment with CIHR definitions than gender (94% vs 12%; p<0.0001). In total, 25 studies used an SGBA for outcomes of interest. Males and females experience different causes of concussion, 60% of studies documented that females had less frequent CT scanning while in the ED, and 57% of studies reported that postconcussion syndrome was more prevalent in females and women. CONCLUSION: This systematic review highlighted that sex is reported more accurately than gender, approximately half of studies did not report either sex and/or gender as demographic information, and one-third of studies did not include SGBA. There were important sex and gender differences in the cause, ED presentation, management and outcomes of concussions. PROSPERO REGISTRATION NUMBER: CRD42021258613.

A neural probe for concurrent real-time measurement of multiple neurochemicals with electrophysiology in multiple brain regions in vivo.

Real-time monitoring of various neurochemicals with high spatial resolution in multiple brain regions in vivo can elucidate neural circuits related to various brain diseases. However, previous systems for monitoring neurochemicals have limitations in observing multiple neurochemicals without crosstalk in real time, and these methods cannot record electrical activity, which is essential for investigating neural circuits. Here, we present a real-time bimodal (RTBM) neural probe that uses monolithically integrated biosensors and multiple shanks to study the connectivity of neural circuits by measuring multiple neurochemicals and electrical neural activity in real time. Using the RTBM probe, we demonstrate concurrent measurements of four neurochemicals-glucose, lactate, choline, and glutamate without cross-talking each other-and electrical activity in real time in vivo. Additionally, we show the functional connectivity between the medial prefrontal cortex and mediodorsal thalamus through the simultaneous measurement of chemical and electrical signals. We expect that our device will contribute to not only elucidating the role of neurochemicals in neural circuits related to brain functions but also developing drugs for various brain diseases related to neurochemicals.

Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice.

Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and juvenile seizure-related death. Ank2-cKO cortical neurons show abnormally increased excitability and firing rate. These changes accompanied decreases in the total level and function of the Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels and the density of these channels in the enlengthened axon initial segment. Importantly, the Kv7 agonist, retigabine, rescued neuronal excitability, juvenile seizure-related death, and hyperactivity in Ank2-cKO mice. These results suggest that Ank2 regulates neuronal excitability by regulating the length of and Kv7 density in the AIS and that Kv7 channelopathy is involved in Ank2-related brain dysfunctions.

Adnp-mutant mice with cognitive inflexibility, CaMKIIα hyperactivity, and synaptic plasticity deficits.

ADNP syndrome, involving the ADNP transcription factor of the SWI/SNF chromatin-remodeling complex, is characterized by developmental delay, intellectual disability, and autism spectrum disorders (ASD). Although Adnp-haploinsufficient (Adnp-HT) mice display various phenotypic deficits, whether these mice display abnormal synaptic functions remain poorly understood. Here, we report synaptic plasticity deficits associated with cognitive inflexibility and CaMKIIα hyperactivity in Adnp-HT mice. These mice show impaired and inflexible contextual learning and memory, additional to social deficits, long after the juvenile-stage decrease of ADNP protein levels to ~10% of the newborn level. The adult Adnp-HT hippocampus shows hyperphosphorylated CaMKIIα and its substrates, including SynGAP1, and excessive long-term potentiation that is normalized by CaMKIIα inhibition. Therefore, Adnp haploinsufficiency in mice leads to cognitive inflexibility involving CaMKIIα hyperphosphorylation and excessive LTP in adults long after its marked expressional decrease in juveniles.

Symmetry Breaking of Human Pluripotent Stem Cells (hPSCs) in Micropattern Generates a Polarized Spinal Cord-Like Organoid (pSCO) with Dorsoventral Organization.

Axis formation and related spatial patterning are initiated by symmetry breaking during development. A geometrically confined culture of human pluripotent stem cells (hPSCs) mimics symmetry breaking and cell patterning. Using this, polarized spinal cord organoids (pSCOs) with a self-organized dorsoventral (DV) organization are generated. The application of caudalization signals promoted regionalized cell differentiation along the radial axis and protrusion morphogenesis in confined hPSC colonies. These detached colonies grew into extended spinal cord-like organoids, which established self-ordered DV patterning along the long axis through the spontaneous expression of polarized DV patterning morphogens. The proportions of dorsal/ventral domains in the pSCOs can be controlled by the changes in the initial size of micropatterns, which altered the ratio of center-edge cells in 2D. In mature pSCOs, highly synchronized neural activity is separately detected in the dorsal and ventral side, indicating functional as well as structural patterning established in the organoids. This study provides a simple and precisely controllable method to generate spatially ordered organoids for the understanding of the biological principles of cell patterning and axis formation during neural development.

Neural mechanism of acute stress regulation by trace aminergic signalling in the lateral habenula in male mice.

Stress management is necessary for vertebrate survival. Chronic stress drives depression by excitation of the lateral habenula (LHb), which silences dopaminergic neurons in the ventral tegmental area (VTA) via GABAergic neuronal projection from the rostromedial tegmental nucleus (RMTg). However, the effect of acute stress on this LHb-RMTg-VTA pathway is not clearly understood. Here, we used fluorescent in situ hybridisation and in vivo electrophysiology in mice to show that LHb aromatic L-amino acid decarboxylase-expressing neurons (D-neurons) are activated by acute stressors and suppress RMTg GABAergic neurons via trace aminergic signalling, thus activating VTA dopaminergic neurons. We show that the LHb regulates RMTg GABAergic neurons biphasically under acute stress. This study, carried out on male mice, has elucidated a molecular mechanism in the efferent LHb-RMTg-VTA pathway whereby trace aminergic signalling enables the brain to manage acute stress by preventing the hypoactivity of VTA dopaminergic neurons.

Formal and informal venous thromboembolism risk assessment and impact on prescribing of thromboprophylaxis: a retrospective cohort study.

BACKGROUND: Hospital-acquired thrombosis (HAT) is a leading cause of preventable death and disability worldwide. HAT includes any venous thromboembolic (VTE) event occurring in-hospital or within 90-days of hospitalisation. Despite availability of evidence-based guidelines for HAT risk assessment and prophylaxis, guidelines are still underutilised. AIM: To determine the proportion of patients who developed HAT that could have been potentially prevented with appropriate VTE risk assessment and prophylaxis at a large public hospital in New Zealand. Additionally, the predictors of VTE risk assessment and thromboprophylaxis were examined. METHOD: VTE patients admitted under general medicine, reablement, general surgery, or orthopaedic surgery service were identified using ICD-10-AM codes. Data were collected on patient characteristics, VTE risk factors, and the thromboprophylaxis regimen prescribed. The hospital VTE guidelines were used to determine rates of VTE risk assessment and the appropriateness of thromboprophylaxis. RESULTS: Of 1302 VTE patients, 213 HATs were identified. Of these, 116 (54%) received VTE risk assessment, and 98 (46%) received thromboprophylaxis. Patients who received VTE risk assessment were 15 times more likely to receive thromboprophylaxis (odds ratio [OR] = 15.4; 95% CI 7.65-30.98) and 2.8 times more likely to receive appropriate thromboprophylaxis (OR = 2.79; 95% CI 1.59-4.89). CONCLUSION: A large proportion of high-risk patients who were admitted to medical, general surgery and reablement services and who developed HAT did not receive VTE risk assessment and thromboprophylaxis during their index admission, demonstrating a significant gap between guideline recommendations and clinical practice. Implementing mandatory VTE risk assessment and adherence to guidelines to improve thromboprophylaxis prescription in hospitalised patients may help reduce the burden of HAT.

Logistic Regression With Machine Learning Sheds Light on the Problematic Sexual Behavior Phenotype.

OBJECTIVES: There has been a longstanding debate about whether the mechanisms involved in problematic sexual behavior (PSB) are similar to those observed in addictive disorders, or related to impulse control or to compulsivity. The aim of this report was to contribute to this debate by investigating the association between PSB, addictive disorders (internet addiction, compulsive buying), measures associated with the construct known as reward deficiency (RDS), and obsessive-compulsive disorder (OCD). METHODS: A Canadian university Office of the Registrar invited 68,846 eligible students and postdoctoral fellows. Of 4710 expressing interest in participating, 3359 completed online questionnaires, and 1801 completed the Mini-International Neuropsychiatric Interview. PSB was measured by combining those screening positive (score at least 6) on the Sexual Addiction Screening Test-Revised Core with those self-reporting PSB. Current mental health condition(s) and childhood trauma were measured by self-report. OCD was assessed by a combination of self-report and Mini-International Neuropsychiatric Interview data. RESULTS: Of 3341 participants, 407 (12.18%) screened positive on the Sexual Addiction Screening Test-Revised Core. On logistic regression, OCD, attention deficit, internet addiction, a family history of PSB, childhood trauma, compulsive buying, and male gender were associated with PSB. On multiple correspondence analysis, OCD appeared to cluster separately from the other measures, and the pattern of data differed by gender. CONCLUSIONS: In our sample, factors that have previously been associated with RDS and OCD are both associated with increased odds of PSB. The factors associated with RDS appear to contribute to a separate data cluster from OCD and to lie closer to PSB.

A Novel Oncodental Collaborative Team: Integrating Expertise for Central Line-Associated Bloodstream Infection Prevention in Pediatric Oncology Patients.

PURPOSE: Pediatric oncology and bone marrow transplant patients are at high risk of infection, and limitations to dental expertise among medical providers render patients vulnerable to central line-associated bloodstream infections from oral pathogens. Traditionally, oral health maintenance relied on patients and bedside nurses; however, routine methods are often suboptimal to prevent central line-associated bloodstream infection in high-risk patients. Limited overlap of medical and dental expertise, and limited dental resources in typical oncology units, prevent optimal oral care for children with cancer, requiring novel solutions to better integrate specialties. METHODS: Here, we outline the creation of a novel Pediatric oncodental team to address oral-systemic infection prevention strategies for high-risk patients. RESULTS: Our oncology and dental teams created a systematic approach for increasing oral surveillance and treatment in select high-risk patients. Supervised pediatric dental residents participated in scheduled oncology rounds, and a permanent oral health educator with a background in dental hygiene was also hired as a dedicated dental professional within our oncology department. CONCLUSION: Our pediatric oncodental team aims to sustain optimal oral complication prevention strategies to reduce the risk of infection, provide education on the significance of the oral-systemic link in cancer care, and improve access and continuity of care.

Effect of a High-Sensitivity Troponin I and Associated Diagnostic Protocol on Emergency Department Length of Stay: A Retrospective Cohort Study.

Background: The objective of this study was to assess the introduction of a high-sensitivity troponin I (hs-TnI) assay and its associated accelerated protocol on emergency department (ED) length of stay (LOS) for patients presenting with chest pain, compared to an accelerated diagnostic protocol using conventional troponin (TnI) testing. Methods: We conducted a retrospective cohort study of all adults with a primary presenting complaint of chest pain of cardiac origin and a Canadian Triage and Acuity Scale score of 2 or 3, between November 8, 2019 and November 9, 2021, to a tertiary-care urban Canadian ED. The primary outcome was ED LOS. Secondary outcomes included consultation proportions and major adverse cardiac events within 30 days of the index ED visit. Results: A total of 2640 patients presenting with chest pain were included, with 1333 in the TnI group and 1307 in the hs-TnI group. Median ED LOS decreased significantly, from 392 minutes for the TnI group, and 371 minutes for the hs-TnI group (median difference = 21 minutes; 95% confidence interval: 5.3, 36.7). The numbers of consultations and admissions were not statistically different between study periods. The major adverse cardiac events outcomes did not change following the implementation of the hs-TnI test (13.6% vs 13.1%; P = 0.71). Conclusions: The implementation of an accelerated chest pain protocol using an hs-TnI assay in a tertiary-care Canadian ED was associated with a modest reduction of LOS for all patients, and a substantial reduction of LOS for patients undergoing serial troponin testing. This strategy was safe, with no increase in adverse outcomes.

Contexte: Cette étude visait à évaluer l'introduction du dosage de la troponine I de haute sensibilité (hs-TnI) et le protocole accéléré qui lui est associé sur la durée des séjours aux urgences dans le cas des patients qui consultent pour une douleur thoracique, comparativement à un protocole diagnostique accéléré faisant appel à un test de troponine classique (TnI). Méthodologie: Nous avons mené une étude de cohorte rétrospective portant sur tous les adultes qui se sont présentés aux urgences d'un établissement urbain de soins tertiaires canadien entre le 8 novembre 2019 et le 9 novembre 2021 principalement pour une douleur thoracique d'origine cardiaque et dont le score était de 2 ou 3 à l'Échelle canadienne de triage et de gravité (ETG). Le principal critère d'évaluation était la durée du séjour au service des urgences. Les critères d'évaluation secondaires comprenaient la fréquence des consultations et les événements cardiaques indésirables majeurs dans les 30 jours ayant suivi la visite de référence aux urgences. Résultats: Au total, 2640 patients qui s'étaient présentés aux urgences pour une douleur thoracique ont été inclus, 1333 se trouvant dans le groupe TnI et 1307 dans le groupe hs-TnI. La durée médiane du séjour aux urgences a diminué considérablement, passant de 392 minutes dans le groupe TnI à 371 minutes dans le groupe hs-TnI (différence médiane de 21 minutes; intervalle de confiance [IC] à 95 % : 5,3-36,7). Les consultations et les admissions n'ont pas affiché de différence statistique entre les périodes de l'étude. Les événements cardiaques indésirables majeurs n'ont pas varié après l'introduction du dosage de la hs-TnI (13,6 % vs 13,1 %; p = 0,71). Conclusions: L'adoption d'un protocole accéléré pour la douleur thoracique à l'aide du dosage de la hs-TnI au service des urgences d'un établissement de soins tertiaires canadien a été associée à une légère réduction de la durée du séjour pour l'ensemble des patients et à une réduction substantielle de cette durée pour les patients soumis à des analyses de la troponine en série. De plus, cette stratégie était sûre sans hausse des événements indésirables.

Sports-Related Concussions in Adults Presenting to Canadian Emergency Departments.

OBJECTIVE: To document the occurrence and recovery outcomes of sports-related concussions (SRCs) presenting to the Emergency Department (ED) in a community-based sample. DESIGN: A prospective observational cohort study was conducted in 3 Canadian hospitals. SETTING: Emergency Department. PATIENTS: Adults (≥17 years) presenting with a concussion to participating EDs with a Glasgow Coma Scale score ≥13 were recruited. INTERVENTIONS: Patient demographics (eg, age and sex), clinical characteristics (eg, history of depression or anxiety), injury characteristics (eg, injury mechanisms and loss of consciousness and duration), and ED management and outcomes (eg, imaging, consultations, and ED length of stay) were collected. MAIN OUTCOME MEASURES: Patients' self-reported persistent concussion symptoms, return to physical activity status, and health-related quality of life at 30 and 90 days after ED discharge. RESULTS: Overall, 248 patients were enrolled, and 25% had a SRC. Patients with SRCs were younger and reported more physical activity before the event. Although most of the patients with SRCs returned to their normal physical activities at 30 days, postconcussive symptoms persisted in 40% at 90 days of follow-up. After adjustment, there was no significant association between SRCs and persistent symptoms; however, patients with concussion from motor vehicle collisions were more likely to have persistent symptoms. CONCLUSION: Although physically active individuals may recover faster after a concussion, patients returning to their physical activities before full resolution of symptoms are at higher risk of persistent symptoms and further injury. Patient-clinician communications and tailored recommendations should be encouraged to guide appropriate acute management of concussions.

Postnatal age-differential ASD-like transcriptomic, synaptic, and behavioral deficits in Myt1l-mutant mice.

Myelin transcription factor 1 like (Myt1l), a zinc-finger transcription factor, promotes neuronal differentiation and is implicated in autism spectrum disorder (ASD) and intellectual disability. However, it remains unclear whether Myt1l promotes neuronal differentiation in vivo and its deficiency in mice leads to disease-related phenotypes. Here, we report that Myt1l-heterozygous mutant (Myt1l-HT) mice display postnatal age-differential ASD-related phenotypes: newborn Myt1l-HT mice, with strong Myt1l expression, show ASD-like transcriptomic changes involving decreased synaptic gene expression and prefrontal excitatory synaptic transmission and altered righting reflex. Juvenile Myt1l-HT mice, with markedly decreased Myt1l expression, display reverse ASD-like transcriptomes, increased prefrontal excitatory transmission, and largely normal behaviors. Adult Myt1l-HT mice show ASD-like transcriptomes involving astrocytic and microglial gene upregulation, increased prefrontal inhibitory transmission, and behavioral deficits. Therefore, Myt1l haploinsufficiency leads to ASD-related phenotypes in newborn mice, which are temporarily normalized in juveniles but re-appear in adults, pointing to continuing phenotypic changes long after a marked decrease of Myt1l expression in juveniles.

Adult re-expression of IRSp53 rescues NMDA receptor function and social behavior in IRSp53-mutant mice.

IRSp53 (or BAIAP2) is an abundant excitatory postsynaptic scaffolding/adaptor protein that is involved in actin regulation and has been implicated in autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder. IRSp53 deletion in mice leads to enhanced NMDA receptor (NMDAR) function and social deficits that are responsive to NMDAR inhibition. However, it remains unclear whether IRSp53 re-expression in the adult IRSp53-mutant mouse brain after the completion of brain development could reverse these synaptic and behavioral dysfunctions. Here we employed a brain-blood barrier (BBB)-penetrant adeno-associated virus (AAV) known as PHP.eB to drive adult IRSp53 re-expression in IRSp53-mutant mice. The adult IRSp53 re-expression normalized social deficits without affecting hyperactivity or anxiety-like behavior. In addition, adult IRSp53 re-expression normalized NMDAR-mediated excitatory synaptic transmission in the medial prefrontal cortex. Our results suggest that adult IRSp53 re-expression can normalize synaptic and behavioral deficits in IRSp53-mutant mice and that BBB-penetrant adult gene re-expression has therapeutic potential.

Early postnatal serotonin modulation prevents adult-stage deficits in Arid1b-deficient mice through synaptic transcriptional reprogramming.

Autism spectrum disorder is characterized by early postnatal symptoms, although little is known about the mechanistic deviations that produce them and whether correcting them has long-lasting preventive effects on adult-stage deficits. ARID1B, a chromatin remodeler implicated in neurodevelopmental disorders, including autism spectrum disorder, exhibits strong embryonic- and early postnatal-stage expression. We report here that Arid1b-happloinsufficient (Arid1b+/-) mice display autistic-like behaviors at juvenile and adult stages accompanied by persistent decreases in excitatory synaptic density and transmission. Chronic treatment of Arid1b+/- mice with fluoxetine, a selective serotonin-reuptake inhibitor, during the first three postnatal weeks prevents synaptic and behavioral deficits in adults. Mechanistically, these rescues accompany transcriptomic changes, including upregulation of FMRP targets and normalization of HDAC4/MEF2A-related transcriptional regulation of the synaptic proteins, SynGAP1 and Arc. These results suggest that chronic modulation of serotonergic receptors during critical early postnatal periods prevents synaptic and behavioral deficits in adult Arid1b+/- mice through transcriptional reprogramming.

A prospective study of patients with low back pain attending a Canadian emergency department: Why they came and what happened?

Low back pain is a common presentation to emergency departments, but the reasons why people choose to attend the emergency department have not been explored. We aimed to fill this gap with this study to understand why persons with low back pain choose to attend the emergency department. Between July 4, 2017 and October 1, 2018, consecutive patients with a complaint of low back pain presenting to the University of Alberta Hospital emergency department were screened. Those enrolled completed a 13-item questionnaire to assess reasons and expectations related to their presentation. Demographics, acuity and disposition were obtained electronically. Factors associated with admission were examined in a logistic regression model. After screening 812 patients, 209 participants met the study criteria. The most common Canadian Triage and Acuity Scale score was 3 (73.2%). Overall, 37 (17.7%) received at least one consultation, 89.0% of participants were discharged home, 9.6% were admitted and 1.4% were transferred. Participants had a median pain intensity of 8/10 and a median daily functioning of 3/10. When asked, 64.6% attended for pain control while 44.5% stated ease of access. Most participants expected to obtain pain medication (67%) and advice (56%). Few attended because of cost savings (3.8%). After adjustment, only advanced age and ambulance arrival were significantly associated with admission. In conclusion, most low back pain patients came to the emergency department for pain control yet few were admitted and the majority did not receive a consultation. Timely alternatives for management of low back pain in the emergency department appear needed, yet are lacking.

Screening tools to identify patients with unmet palliative care needs in the emergency department: A systematic review.

OBJECTIVES: This systematic review identified and assessed psychometric properties of the available screening tools to identify patients with unmet palliative care (PC) needs in the emergency department (ED). METHODS: A comprehensive search of electronic databases and the gray literature was conducted. Two independent reviewers completed study screening and inclusion, data extraction, and quality assessment. A descriptive summary of the results was reported using median of medians and interquartile ranges (IQRs). RESULTS: A total of 35 studies were included, involving the assessment of 14 unique screening tools. The most commonly used screening tool was the surprise question (SQ; n = 12 studies), followed by the Palliative Care and Rapid Emergency Screening (P-CaRES) tool (n = 8), and the screening for palliative and end-of-life care needs in the emergency department (SPEED) instrument (n = 4). Twelve of the included studies reported on the psychometric properties of the screening tools, of which eight of these studies assessed the performance of the SQ to predict patient mortality. Overall, the median sensitivity (63%, IQR 38%-78%) and specificity (75%, IQR 57%-84%) of the SQ to predict mortality at 1 or 12 months was moderate. While the median positive predictive value of the SQ was low (32%, IQR 16%-40%), the median negative predictive value was high (91%, IQR 88%-95%). Across the studies, the proportion of patients identified as having unmet PC based on the criteria of the screening tools ranged from 5% to 83%. CONCLUSIONS: This review identified 14 unique screening tools used to identify adult patients with unmet PC needs in the ED. One screening tool, the SQ, was found to have moderate sensitivity and specificity to accurately predict future patient mortality. Additional research is needed to better understand the clinical value of this and the other available tools prior to their widespread implementation.