Evidence from preclinical and clinical studies suggests that human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) may be useful in treating heart failure and acute myocardial infarction (MI). However, the effects of stem cell therapy on patients with heart failure remain the subject of ongoing controversy, and the safety and effectiveness of HUC-MSCs therapy have not yet been proven. To date, there has been no systematic overview and meta-analysis of clinical studies using HUC-MSCs therapy for heart failure and MI. The purpose of this study is to assess the safety and efficacy of HUC-MSC therapy versus a placebo in patients with heart failure and MI.While preparing this systematic review and meta-analysis, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A computer literature search of PubMed was performed. We considered randomized controlled trials (RCTs) that reported data on the safety and efficacy of HUC-MSC transplantation in patients with heart failure and MI. Two investigators independently searched the literature, extracted data, and rated the quality of the included research. Pooled data were analyzed using the fixed-effect model or the random-effect model in Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The primary outcome was ejection fraction (EF), whereas the secondary outcomes were readmission and mortality rates.Three RCTs (201 patients) were included in this meta-analysis. The overall effect did not favor either of the two groups in terms of risk of readmission  = 0.22-1.15, p = 0.10) as well as mortality rate . However, there was an improvement in EF in patients who received HUC-MSCs compared to placebo after 12 months of transplantation (mean difference (MD) = 3.21, 95% CI = 2.91-3.51, p < 0.00001). At the six-month follow-up period, there was no significant improvement in EF , p = 0.43), indicating that the duration of follow-up can shape the response to therapy.Our findings indicate that HUC-MSC transplantation can improve EF but has no meaningful effect on readmission or mortality rates. Existing evidence is insufficient to confirm the efficacy of HUC-MSCs for broader therapeutic applications. Therefore, additional double-blind RCTs with larger sample sizes are required. Cardiovascular diseases (CVDs) are a global health burden of grave proportions ,2. CVDs There is growing evidence that cell types such as bone marrow mononuclear cells, mesenchymal stem cells (MSCs), and cardiac stem cells (CSCs) influence the injured heart via paracrine or regenerative pathways -11. HumaDue to their capacity for self-renewal and multi-lineage differentiation into a variety of regenerative-promoting specialized cell types, HUC-MSCs have been intensively researched in this context ,19. RelaClinical trials involving HUC-MSCs in the treatment of CVDs are controversial but encouraging. Some have yielded neutral results. Others were undertaken with small sample sizes. Moreover, several questions, such as the appropriate dose of stem cells that must be injected, the optimal mode of cell delivery, and the optimal delivery schedule to enhance recovery of heart function after myocardial infarction (MI) or heart failure, remain unanswered. Consequently, a meta-analysis was performed to determine the true impact of these cells. There is a lack of clinical evidence about the efficacy of HUC-MSC transplantation for patients with heart disease. This meta-analysis aims to synthesize evidence from published randomized controlled trials (RCTs) about the safety and efficacy of HUC-MSC transplantation for patients with heart failure and MI.MethodologyThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards were adhered to in the development of this review and meta-analysis.Inclusion and Exclusion CriteriaStudies satisfying the following criteria were included in the present study: (1) parallel, randomized, controlled trials investigating the safety and efficacy of HUC-MSCs for cardiac repair such as heart failure and MI; (2) studies whose population included adult patients with symptomatic cardiac disease; (3) studies with HUC-MSC transplantation intervention; (4) studies with a control group taking placebo; and (5) studies reporting the mean change in left ventricular ejection fraction (LVEF), infarct size, six-minute walk distance, and functional status, adverse effects from baseline to the end of the follow-up period. We excluded studies that were not accessible in the English language, as well as thesis papers, conference abstracts, and studies for which the data were not retrievable for extraction and analysis.Literature Search StrategyA literature search of PubMed was conducted up to December 2022. For the sensitive search strategy, we used “clinical trial” as a filter for our search. We also used the MeSH database and the following search queries: “umbilical cord-derived mesenchymal stromal cells AND heart” OR “umbilical cord-derived mesenchymal stem cells AND ischemic heart disease” OR “Wharton’s jelly-derived mesenchymal stem cells AND acute myocardial infarction” OR “umbilical cord-derived mesenchymal stem cell AND coronary artery disease” OR “umbilical cord-derived mesenchymal stem cell AND heart failure.”The titles and abstracts of the retrieved citations were checked by two authors. The process of eligibility screening was conducted in a two-step manner. The initial stage involved the screening of abstracts to determine their eligibility. Subsequently, the second stage entailed retrieving and screening full-text articles of the acceptable abstracts to ascertain their suitability for inclusion in the meta-analysis.Data ExtractionThe data extraction process was conducted by two authors independently via an online data extraction form. The data that were extracted encompassed the following components: (1) the design of the study; (2) the population that was studied; (3) the domains related to the risk of bias; and (4) the outcomes of the investigation, which comprised the mean change in the LVEF, the size of the infarct, the distance covered in a six-minute walk, the functional status, and any adverse effects seen. Disagreements were addressed through the authoritative input of the senior author.Quality AssessmentQuality assessment of the retrieved RCTs was conducted according to the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0, which was last updated in March 2011. The quality assessment table supplied in Part 2, Chapter 8.5 of the same handbook was utilized for this purpose. The Cochrane risk of bias assessment tool encompasses several domains that are crucial for evaluating the quality of a study. These domains include sequence generation, allocation sequence concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other possible sources of bias. The evaluation conducted by the authors is categorized as “Low risk,” “High risk,” or “Unclear risk” in terms of bias.Subgroup AnalysisFor the outcome of LVEF improvement, data are presented in two subgroups according to the follow-up period after HUC-MSCs transplantation: the first subgroup at 12-month follow-up and the second subgroup at six-month follow-up.Assessment of Heterogeneity2) and chi-square tests. The chi-square test was utilized to assess the presence of statistically significant heterogeneity, while the I2 statistic was employed to quantify the extent of heterogeneity in the effect size. The assessment and interpretation of heterogeneity were conducted following the guidelines outlined in the Cochrane Handbook of Systematic Reviews and Meta-analysis (Chapter 9). In this manual, a critical value of less than 0.1 indicates considerable heterogeneity for the chi-square test. The I2 test is interpreted as follows: a range of 0-40% may not be of great importance, 30-60% may indicate moderate heterogeneity, and 50-90% may suggest substantial heterogeneity. The utilization of the random-effect model was implemented in cases where significant heterogeneity existed.The evaluation of heterogeneity encompassed a comprehensive examination of the forest plots, alongside the application of statistical measures such as I-square (IData SynthesisImprovement in ejection fraction (EF) was pooled as mean difference (MD) in a meta-analysis model in a random-effect model while readmission and mortality were pooled as risk ratio (RR) using the Mantel-Haenszel (M-H) method. The random-effect model was used due to the heterogeneity of some included studies while the fixed-effect model was used under the assumption that the included studies were homogeneous and comparable in terms of study design, quality, and measures of treatment effect. We used Review Manager 5.3 for Windows.Publication BiasAccording to Egger and colleagues ,31, publResultsSearch ResultsA search conducted on PubMed utilizing the NCBI filter “clinical trial” yielded a total of nine clinical studies. After conducting the title and abstract screening process, six articles met the criteria for full-text screening. Among the available options, three clinical trials encompassing a combined cohort of 201 individuals were deemed suitable for inclusion in the final analysis. Three of the trials were excluded because the composition of the intervention and control groups did not meet the inclusion criteria outlined in our meta-analysis, as depicted in the PRISMA flow diagram 2 = 0%). In the six-month follow-up subgroup, the overall effect did not favor the HUC-MSC group over the placebo group ; the pooled studies were heterogenous .Left ventricular ejection fraction: Subgroup analysis of the two subgroups was performed according to the follow-up period after HUC-MSC transplantation Figure . In the 2 = 0%).Readmission: There was no statistically significant difference in readmission between the HUC-MSC group and the placebo group  .Mortality: There was no statistically significant difference in mortality between the HUC-MSC group and placebo group  Figure ; the pooDiscussionSummary of Main ResultsAlthough numerous preclinical studies have demonstrated the advantages of HUC-MSC treatment for animal models with heart failure or MI ,29, few While the improvement in LVEF is a significant finding in the context of stem cell therapy for heart failure and MI, it is essential to bridge the gap between statistical significance and the clinical implications of this improvement. The clinical relevance of an increased LVEF should be assessed not only in terms of statistical values but also in its impact on patients’ lives.Symptom alleviation: An increase in LVEF may correspond to a reduction in symptoms experienced by patients, such as breathlessness, fatigue, or exercise intolerance. It is crucial to investigate whether the improvement in LVEF translates into a noticeable reduction in these symptoms, which can significantly enhance a patient’s quality of life.Quality of life: A paramount measure of clinical relevance is the impact on the overall quality of life. Assess whether patients who received HUC-MSC therapy report an improved quality of life, including their ability to perform daily activities, engage in social interactions, and experience an enhanced sense of well-being. Measuring quality of life may require standardized questionnaires or interviews.Functional outcomes: In addition to LVEF, evaluating functional outcomes is vital. Patients’ capacity to perform physical tasks, such as the six-minute walk test, should be explored. An increase in LVEF might manifest as enhanced physical abilities, indicating a genuine clinical benefit.Hospitalization rates: Examine whether there is any impact on hospitalization rates. A decrease in hospital readmissions could indicate that patients are experiencing fewer severe cardiac events, reflecting a tangible improvement in their health and a reduction in the economic burden of healthcare.Long-term outcomes: Consider the long-term implications of improved LVEF. Determine whether this improvement translates into a better long-term prognosis, including reduced mortality and fewer adverse cardiac events. Assess the durability of the benefits and their continued impact on patients’ lives.Duration of Follow-Up2 = 0%).The duration of follow-up following HUC-MSC transplantation varied between trials and appeared to have a significant impact on the therapeutic outcome. Gao et al. reported their findings at a 12-month follow-up while Zhao et al. reported at a six-month follow-up ,33. BartQuality of EvidenceBecause it is based on RCTs, the quality of this evidence is reliable. The techniques of search and the eligibility criteria were established. To prepare for this study, we used the PRISMA checklist and followed the Cochrane Handbook for Systematic Reviews of Interventions strictly.LimitationsThe limitations of this meta-analysis include limited data, with only three small-scale RCTs involving a total of 201 patients, potentially limiting the generalizability of findings. Heterogeneous follow-up durations across the included studies (six months and 12 months) resulted in varying results and made it challenging to draw definitive conclusions. A small number of studies prevented a reliable assessment of publication bias, potentially affecting the accuracy of the overall conclusions. The risk of bias in some included studies across different domains could introduce bias into the meta-analysis. Additionally, the analysis primarily focused on LVEF, readmission rates, and mortality rates, neglecting other crucial clinical outcomes such as quality of life and symptom improvement. Variations in patient characteristics across the included studies may impact treatment responses, and this heterogeneity was not extensively discussed. The longest follow-up period in the studies was 12 months, limiting the assessment of long-term effects and safety considerations, and the findings may not apply to a broader range of patients with heart failure and MI due to the specific characteristics of the study populations.The economic considerations associated with stem cell therapy in the treatment of heart failure and acute MI are multifaceted. Stem cell interventions pose significant economic implications that warrant careful examination for feasibility and broader implementation. Key economic factors include the costs of cell acquisition and processing, where sophisticated laboratory techniques and quality control measures contribute substantially. Additionally, treatment administration costs, encompassing expertise, medical facilities, and specialized equipment, add to the economic considerations. Post-treatment, follow-up, and monitoring expenses play a crucial role in involving medical appointments, diagnostic tests, and potential imaging studies. Comparative cost-effectiveness analysis against standard treatments is vital for informed decision-making.Future directionsAs this meta-analysis contributes valuable insights into the efficacy of HUC-MSC therapy for heart failure and acute MI, it also points toward several promising avenues for future research. Future studies should extend the follow-up duration beyond the 12-month mark to assess the durability and sustainability of observed improvements and determine whether the initial increase in LVEF results in long-term clinical benefits, such as reduced mortality and fewer cardiac events. Investigating the impact of HUC-MSC therapy on specific patient subgroups, including different age groups, genders, comorbidity profiles, or disease severity, can guide more personalized treatment approaches. Incorporating robust quality-of-life assessments is essential to provide a comprehensive view of how HUC-MSC therapy affects patients’ daily lives, well-being, and overall satisfaction. Assessing the therapy’s impact on functional outcomes beyond LVEF, such as exercise tolerance, cardiac function, and the ability to perform daily activities, can shed light on the practical significance of LVEF improvements. Exploring the potential synergy of HUC-MSC therapy with other interventions, determining optimal dosage and timing, delving deeper into the mechanisms through which HUC-MSCs exert their effects, and monitoring patients for long-term safety and adverse effects are important research avenues. Focusing on patient-centered outcomes that matter most to patients and developing clinical guidelines and standardized protocols for HUC-MSC therapy will ensure consistency in treatment approaches and address ethical considerations as stem cell therapies evolve.Preclinical research utilizing HUC-MSCs to treat heart failure or MI has yielded provocative results, paving the path for their use in clinical trials. Our meta-analysis reveals that HUC-MSCs can enhance LVEF in patients with heart failure 12 months after transplantation. However, additional large-scale, randomized, double-blind studies are required to establish the safety and efficacy of HUC-MSC therapy in patients with heart failure and MI and to demonstrate whether statistical significance translates into clinical benefit.


Three coronaviruses have emerged in the past two decades . They represent ideal examples of the One Health concept Hemida, . This coAl-Khalaifah et al. explored the relationship between avian CoV and relation with mammalian SARS-CoV2. The authors found that the avian and mammalian coronaviruses exhibit genetic and antigenic distinctions, making it improbable for poultry to serve as a vector for transmitting these coronaviruses. Fortunately, no substantiated evidence has indicated the potential cross-species transmission from human to bird despite the established transmission of SARS-CoV-2 from bats to humans.Identifying the potential reservoir/es of SARS-CoV-2 is essential to prevent future infections and safeguard our food supply's security and stability. We approved and published four research articles for the current Research Topic. Zong et al.).The impact of bacterial coinfection with COVID-19 infection was assessed in the hospital. The study was the result of contradicting findings from the various studies that pointed out that the proportions of bacterial coinfection were very low . They are analyzing microbial abundance and the metabolic profiling of patients enhanced microbiome profiling's predictive potential for clinical outcomes. This underscores the oropharyngeal microbiome's potential diagnostic and therapeutic applications in combating respiratory viruses like SARS-CoV-2.In another study, investigators established a link between COVID-19 respiratory illness and oropharyngeal microbiome severity. Authors have found that metabolic pathways associated with bacterial products may influence disease course positively . Results showed that the SARS-CoV-2 RNA decayed faster at 20°C than at 4°C and was detectable for at least 29 days, indicating evidence for the persistence of viral RNA in site-specific raw sewage water. This is particularly important for laboratories with limited resources and throughput, and sample storage is unavoidable. The study indicates an urgent need for attention to the examination of the decay of SARS-CoV-2 RNA at higher concentration levels and higher temperatures for a longer time.The persistence of SARS-CoV-2 and Pepper mild mottle virus (PMMoV) RNA in raw sewage from university dorms was investigated using real-time quantitative PCR (The vigilant monitoring of common diseases with pandemic potentials, such as influenza and coronaviruses, is highly encouraged. Adaptation of the One Health-based control strategies would be among the critical measures to mitigate the risk of any potential future pandemics (Hemida and Alnaeem, MH: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Validation, Visualization, Writing – original draft, Writing – review & editing. DE: Conceptualization, Data curation, Investigation, Methodology, Writing – original draft, Writing – review & editing. YM: Conceptualization, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft, Writing – review & editing.


Amphimedon queenslandica. Although sponges do not possess a nervous system, A. queenslandica expresses rhodopsin class G-protein-coupled receptors that are structurally similar to dopamine and trace amine receptors. When sponge larvae, which express these receptors, are exposed to agonists and antagonists of bilaterian dopamine and trace amine receptors, we observe marked changes in larval phototactic swimming behaviour, consistent with the sponge being competent to recognise and respond to symbiont-derived trace amine signals. These results indicate that monoamines synthesised by bacterial symbionts may be able to influence the physiology of the host sponge.Interkingdom signalling within a holobiont allows host and symbionts to communicate and to regulate each other’s physiological and developmental states. Here we show that a suite of signalling molecules that function as neurotransmitters and neuromodulators in most animals with nervous systems, specifically dopamine and trace amines, are produced exclusively by the bacterial symbionts of the demosponge  Gut miceceptors . Througheceptors .These observed interactions between bacterial and human cells in the gut and elsewhere raises the possibility that neurotransmitter signalling was co-opted from a more ancestral animal-bacterial symbiont signalling system that predates the origin of the nerve cell . This hyTo further investigate the hypothesis that neurosignalling evolved from an ancestral animal-bacterial signalling system, here we seek evidence from sponges (phylum Porifera), one of the earliest-diverging phyletic lineages of extant animals . SpongesAmphimedon queenslandica requires the production of its precursor, arginine, by its horizontally-inherited symbiotic bacteria , rat (Rattus norvegicus) and fruit fly (Drosophila melanogaster) sequences using web-based Clustal Omega (Transmembrane (TM) domains were identified in potential dopamine (DRD) or trace amine (TAAR)-like receptor coding sequences using TMHMM Server v. 2.0 . GPCR toal Omega , so thatA. queenslandica DRD- and TAAR-like genes were characterized using previously published developmental and cell type RNA-Seq data sets  (The expression of A435744) . All rawA435744) . Raw expA435744) . ReplicaA435744) .Amphimedon queenlandica were collected from Heron Island Reef, southern Great Barrier Reef, Australia  and maintained in a closed aquarium system as described in −2 s−1 at the bright and dark ends, respectively , because the time course of movement through the experimental chamber was unlikely to be linear, and the smooth splines used by BGAMs can flexibly model nonlinear relationships. The response variable was the number of larvae in each quartile at each observation time, leading to a cumulative logit model. We modelled the relationship between the number of larvae in each quartile over time, for each agonist and antagonist  treatment, plus a control in which no drug was added. We fitted 4 models, which consisted of a common time course for all drug treatments versus a treatment-specific time course, and equidistant thresholds versus flexible thresholds. The hypothesis of equidistant thresholds determines whether the quartile widths, as perceived by the larvae, are all equal. As this was how the experimental chamber was constructed, we expected this to be the case. Each experimental run was treated as a random effect. All models were fitted using the brms package for R , 2018.All models were run with the same default improper flat priors, 4 chains each with 4,000 iterations  for a total of 12,000 post-warm up draws. The leave-one-out (LOO) information criterion was computed for all models, and posterior model weights based on the LOOIC were examined to determine the relative support for each model. For the two best models, we performed posterior-predictive plots to determine whether the models could produce data that “looked like” the observed data. Model diagnostics and plotting was conducted using brms , 2018.AqS1, AqS2 and AqS3, can comprise over 95% of total bacterial abundance in A. queenslandica larvae  and His192  and Aqu2.1.23882 (AquDRD5-like)   and Aq-Rho-C (for AquDRD1)   that areAR-like) , has higAquDRD1-like (Aqu2.1.30477) encodes seven TM domains, with the 7th domain being predicted based on hydrophobicity and topology of the C-terminal region from Ile-249 to Tyr-273  encodes five TM domains, and assessment of 1.5 kb flanking sequence in each direction did not uncover additional TMs. AquDRD5-like nonetheless possesses hallmarks of dopamine receptors, including Asp in TM3, two Ser in TM5, and a N-glycosylation site at the N-terminus. It is unclear whether the AquDRD5-like coding sequence is incomplete and if this gene model encodes a functional receptor. AquTAAR-like (Aqu2.1.16444) encodes seven TM domains, and has a sequence and structure most similar to different members of the TAAR-like receptor family. Tyr-273 . AquDRD1er DRD1s . Mammalier DRD1s . AquDRD5AquDRD1-, AquDRD5- and AquTAAR-like expression through development and in the adult reveals that AquDRD1-like is the most highly and widely expressed of the three genes  postlarvae and when choanocyte chambers begin to form later in metamorphosis  cells, which play a major role in larval swimming direction   .We first determined the stage of larval development that has the highest sensitivity to light by subjecting three different aged cohorts  to a light gradient . This anWe then compared the normal phototactic and swimming behaviours of 4–6 hpe larvae with similar aged larvae exposed to DRD and TAAR agonists and antagonists . Of the The time courses of larval movement between quartiles  show thaThe DRD agonist rotigotine hydrochloride and the DRD antagonist flupenthixol dihydrochloride both had only a very mild effect on larval phototactic swimming behaviour compared to the FSW control, and indeed were similar to each other –D. The tAmphimedon queenslandica appears to be able to respond to bacterial-derived dopamine and trace amines, which are known to function as neurotransmitters and neuromodulators in other animals. This sponge has an estimated 130 rhodopsin class GPCRs (Rh-GPCRs), many of which comprise sponge-specific clades  and thus appears incapable of decarboxylating L-DOPA and aromatic amino acids to produce dopamine and trace amines. The gene encoding this ancient enzyme is missing from other, but not all, demosponges . In contrast, two of three primary vertically-inherited bacterial symbionts in A. queenslandica, AqS1 and AqS2, possess and express aadc and hdc genes  and one putative TAAR-like (AquTAAR-like) genes in A. queenslandica genome based on sequence and transmembrane-loop similarities to bilaterian DRDs and TAARs. These sequence and structural similarities to bilaterian DRDs and TAARs probably evolved independently. TAARs have only been reported in vertebrates  appear to have been present in the shared ancestor of animals, fungi and other opisthokonts, and have independently expanded in sponges . The A. nd TAARs , althougtebrates , consistreceptor . Amino aA. queenslandica can be influenced by dopamine and trace amines potentially originating from its vertically-inherited bacterial symbionts, we subjected swimming larvae to known bilaterian agonists and antagonists of DRD and TAAR-likes. The expression of AquDRD1-, AquDRD5- and AquTAAR-like in posterior pole pigment ring cells and tissues, which are responsible for directing larvae away from the light : the ctenophores; sponges; and parahoxozoans  . MinimalRecognisable nervous systems exist in ctenophores and parahoxozoans, although neural cell structure and composition differs markedly between representatives of these lineages . SpongesA. queenslandica larval behaviour, potentially via Rh-GPCRs and their downstream signal transducers, indicates that these known neurotransmitters and neuromodulators can be interkingdom signals even in an animal without neurons. This raises the possibility that symbiont-host communication in stem metazoans contributed to the origin of the disparate nervous systems and aneural signalling systems present in the three basal lineages. This interkingdom signalling may have emerged as an outcome of another deeply ancient system for detecting extracellular signals, the innate immune system, which discriminates self from nonself, and symbionts from pathogens and food  can be found in the article/SD and BD conceptualized this project and the methodological strategies, except for statistical methods that were conceptualized by SB. XX and AV conducted all bioinformatic analyses and experimental assays, with assistance from HY. SB conducted all statistical analyses. AV, SD, BD, XX, and SB prepared the original draft of text and figures. BD and SD finalised the drafts. All authors read and approved the final manuscript.


The target audiences for this team-based learning are emergency medicine and emergency medicine-pediatric resident physicians.Pediatric seizure is a common presenting complaint in the emergency department. It is said that over 470,000 children have a diagnosed seizure disorderBy the end of this TBL session, learners should be able to:Define features of simple versus complex febrile seizureDiscuss which patients with seizure may require further diagnostic workupSummarize a discharge discussion for a patient with simple febrile seizuresIdentify a differential diagnosis for pediatric patients presenting with seizureDefine features of status epilepticusReview an algorithm for the pharmacologic management of status epilepticusIndicate medication dosing and routes of various benzodiazepine treatmentsObtain a thorough history in an infant patient with seizures to recognize hyponatremia due to improperly prepared formulaChoose the appropriate treatment for a patient with a hyponatremic seizureDescribe the anatomy of a ventriculoperitoneal (VP) shuntRelate a differential diagnosis of VP shunt malfunctionCompare and contrast the neuroimaging options for a patient with a VP shuntThis team-based learning is a classic TBL because it contains learner responsible content (LRC), an individual readiness assessment test (iRAT), a multiple-choice group RAT (gRAT) with immediate feedback assessment technique (IF/AT), and a group application exercise (GAE).We received formative feedback through conversations with learners afterwards, who stated they enjoyed the activity and felt it was highly useful for their learning; in addition, instructors discussed after the session and made changes accordingly.We collected verbal feedback from instructors and learners after the session. Learners and instructors felt that it was very successful with limited modifications, in particular, the need for more time to complete the activity. Therefore, we suggest a 90 minute rather than 60-minute timeframe to adequately cover all material.Pediatric seizure is a common complaint in the emergency department. It can be a difficult subject for the emergency medicine resident to master based on the variety of presentations. Indeed, the cause, management, and disposition may vary greatly; the etiology may range from benign to life-threatening, sometimes requiring minimal and at other times an extensive workup, with an ultimate disposition of either discharge home or admission to a pediatric intensive care unit. Therefore, team-based learning is well-suited to work through some of the complexities of such cases, and we found this educational session to be highly effective.Pediatric seizure, simple febrile seizure, complex febrile seizure, status epilepticus, hyponatremic seizure, ventriculoperitoneal (VP) shunt, team-based learning. Learner Audience:Interns, junior residents, senior residentsTime Required for Implementation:Instructor Preparation: 60–90 minutesLearner Responsible Content: 0–60 minutesIn Class Time: 90 minutesRecommended Number of Learners per Instructor:While this cTBL can be taught with only one instructor, ideally, there will be additional facilitators to interact with small groups during the group application exercise.Therefore, it is recommended to have 1 instructor per every 10–20 learners.Topics:Pediatric seizure, simple febrile seizure, complex febrile seizure, status epilepticus, hyponatremic seizure, ventriculoperitoneal (VP) shunt, team-based learning.Objectives:By the end of this TBL session, learners should be able to:Define features of simple versus complex febrile seizureDiscuss which patients with seizure may require further diagnostic workupSummarize a discharge discussion for a patient with simple febrile seizuresIdentify a differential diagnosis for pediatric patient presenting with seizureDefine features of status epilepticusReview an algorithm for the pharmacologic management of status epilepticusIndicate medication dosing and routes of various benzodiazepine treatmentsObtain a thorough history in an infant patient with seizures to recognize hyponatremia due to improperly prepared formulaChoose the appropriate treatment for a patient with a hyponatremic seizureDescribe the anatomy of a ventriculoperitoneal (VP) shuntRelate a differential diagnosis of VP shunt malfunctionCompare and contrast the neuroimaging options for a patient with a VP shuntPediatric seizure is a common complaint in the emergency department. It can be a difficult subject for the emergency medicine resident to master based on the variety of presentations. Indeed, the cause, management, and disposition may vary greatly; the etiology may range from benign to life-threatening, sometimes requiring minimal and at other times an extensive workup, with an ultimate disposition of either discharge home or admission to a pediatric intensive care unit. Therefore, team-based learning is well-suited to work through some of the complexities of such cases, including simple versus complex febrile seizures , a pediatric patient in status epilepticus , the treatment of an infant with a hyponatremic seizure who ultimately is receiving watered-down infant formula (objectives 8 and 9), and unique situations which may predispose a patient to seizure, such as a ventriculoperitoneal shunt . Building from simple definition to more complex decisions, including a treatment algorithm and disposition, these cases provide emergency medicine resident physicians with dedicated practice on managing these cases.https://emergencymedicinecases.com/emergency-management-of-pediatric-seizures/. Published November 2015. Accessed May 30, 2019.Richer L, Mikrogianakis A, Helman A. Episode 73: Emergency Management of Pediatric Seizures. Emergency Medicine Cases. Pediatrics. 2008;121(6):1281–1286.Clinical Report of the American Academy of Pediatrics. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. http://www.emdocs.net/complications-csf-shunts-ed-presentations-evaluation-management/. Published November 2017. Accessed May 31, 2019.Grenga P, Bodkin R, Rotoli J, Silberstein H. Complications of CSF Shunts: ED Presentations, Evaluation and Management. emDocs. Prior to the session, learners should review the following materials:https://emergencymedicinecases.com/emergency-management-of-pediatric-seizures/. Published November 2015. Accessed May 30, 2019.Richer, L, Mikrogianakis, A, Helman A. Episode 73: Emergency Management of Pediatric Seizures. Emergency Medicine Cases. http://www.emdocs.net/complications-csf-shunts-ed-presentations-evaluation-management/. Published November 2017. Accessed May 31, 2019.Grenga P, Bodkin R, Rotoli J, Silberstein H. Complications of CSF Shunts: ED Presentations, Evaluation and Management. emDocs. Our team-based learning was conducted in the format suggested below. While no formal assessment was collected, we received formative feedback through conversations with learners afterwards, who stated they enjoyed the activity and felt it was useful for their learning. Based on the instructor discussions after the activity, it was felt to be successful with limited modifications such as the need for more time; therefore, we suggest a 90 minute rather than 60-minute timeframe to adequately cover all material. Additionally, it is highly recommended that you have each group start with a different case, thus ensuring all cases are covered and each group participates in group discussion.Instructions for implementation:Prior to the session, the instructor should prepare materials:One individual readiness assessment test (iRAT) per learnerOne group readiness assessment test (gRAT) per 3–5 learners (one per group)One group application exercise (GAE) per 3–5 learners (one per group)Copies of all materials, including the keys, for each instructorYou will need approximately 90 minutes to conduct the session. We suggest the following timeline:Introduce session (1 minute)The instructor hands out the iRAT to all learners and have them complete it individually (5–10 minutes)See gRAT section for how to prepare a gRAT.The instructor assigns learners into groups of 3–5. Ideally, a mix of level of learners is best . Groups complete the gRAT (5–10 minutes). The instructor briefly reviews answers for the gRAT (5–10 minutes); a suggested format is to call on groups one at a time to give their answer. Note: this is NOT a time for in-depth discussion of questions, but rather just pre-assessment review of answers. Assure learners that material will be covered in greater detail during cases.Groups complete the GAE (30 minutes); again, we suggest having all groups complete all cases whenever possible; however, you may assign some groups to start at case 1, some groups to start at case 2, some groups to start at case 3, etc., so that all cases are covered when time is called.Review answers from the GAE (30 minutes); a suggested format is to call on groups one at a time to answer each question. Note that the instructor materials provide enhanced answers in case of questions, and not all material will need to be covered.Hand out post-test learning sheet.


Stimulation of the peripheral visual field has been previously reported as beneficial for cognitive performance in ADHD. This study assesses the safety and efficacy of a novel intervention involving peripheral visual stimuli in managing attention deficit hyperactivity disorder (ADHD).One hundred and eight adults, 18–40 years old, with ADHD, were enrolled in a two-month open-label study. The intervention  consisted of standard eyeglasses with personalized peripheral visual stimuli embedded on the lenses. Participants were assessed at baseline and at the end of the study with self-report measures of ADHD symptoms , and executive functions . A computerized test of continuous performance  was tested at baseline with standard eyeglasses and at the end of study using Neuro-glasses. The Clinical Global Impression-Improvement scale (CGI-I) was assessed at the intervention endpoint. Safety was monitored by documentation of adverse events.p = 0.037) and metacognitive functions concerning self-management and performance monitoring . A continuous-performance test (CPT-3) indicated significant improvement in detectability  and reduced commission errors (p = 0.004), suggesting that the Neuro-glasses have positive effects on response inhibition. Sixty-two percent of the participants met the response criteria assessed by a clinician (CGI-I). No major adverse events were reported.The efficacy analysis included 97 participants. Significant improvements were demonstrated in self-reported measures of inattentive symptoms (ASRS inattentive index; Neuro-glasses may offer a safe and effective approach to managing adult ADHD. Results encourage future controlled efficacy studies to confirm current findings in adults and possibly children with ADHD.Clinical trial registration: https://www.clinicaltrials.gov/, Identifier NCT05777785. Attention deficit hyperactivity disorder (ADHD) poses a significant public health problem estimated to affect up to 11% of children worldwide . SymptomAlthough ADHD has a wide range of adverse outcomes, it is one of the most treatable neurobehavioral disorders. Stimulants, such as amphetamines and methylphenidates, are a common ADHD treatment with documented safety and efficacy , 6. NeveIn this study, we use novel glasses, i.e., Neuro-glasses, as an intervention for treating adults with ADHD. It is worth noting that ADHD has been found to be associated with various visual problems and oculomotor abnormalities . A recenPeripheral vision provides essential information concerning our surroundings. It has a survival function as it guides and relates us to the world around us, showing high sensitivity to movement and brightness changes in the visual scene , 14. AltGiven the key role of peripheral vision in monitoring the environment and facilitating rapid detection of changes in the visual scene, it is expected to affect the allocation of attentional resources. Peripheral vision allows us to react quickly and shift attention to adjust our visually guided behavior to the visual scene. Without sufficient peripheral vision providing the visual context in which objects exist, it is difficult to distinguish relevant from nonrelevant information , 17–19. Previous studies have shown that peripheral stimuli external to a task often influence performance , 19–21. The beneficial effect of glasses using peripheral visual stimulation was previously reported in patients with chronic dizziness . It was Eligible participants included adults aged 18 to 40 with a documented history of ADHD diagnosis. The upper age limit was predetermined to avoid age-related cognitive and visual decline. Exclusion criteria were: 1) any psychiatric or neurological comorbidity , 2) concomitant use of ADHD medications  4 weeks before entering the study, and 3) undergoing neurofeedback or cognitive training treatment.This was a two-month, open-label study in which eligible ADHD-diagnosed adults were provided with a pair of Neuro-glasses featuring a personalized visual stimuli pattern for each participant. A baseline assessment of the participants’ ADHD clinical profile pre-intervention included the Adult ADHD Self-Report Scale ASRS;  and the A follow-up assessment at the end of the intervention re-assessed ADHD performance on the ASRS and BRIEF-A questionaries. In addition, participants completed the CPT-3 test while wearing their Neuro-glasses.The Clinical Global Impression-Improvement CGI-I;  rating s™, supplied by VIZO Specs Ltd.) consisted of a standard eyeglasses frame and standard optic lenses with semi-transparent marking stimuli, a few millimeters in size, embedded on the lenses  sampling at 150 Hz with a 23.8-inch display mounted on top  and viewed at 60 cm distance. The tests were carried out using E-Prime 3.0  running on a standard personal computer . Eye-tracking parameters such as oculomotor reaction time and pupil size, as well as behavioral measures of time and accuracy, were collected and processed by VIZO’s proprietary cloud-based system to determine the optimal number and size of the stimuli and their positioning in the peripheral visual field.The outcome measures provide a broad assessment of ADHD symptoms, executive functions, global functioning, and measures of attention and impulsivity. The assessment involved self-report questionnaires, clinician evaluation, and a task-oriented computerized assessment.The Adult ADHD Self-Report Scale ASRS;  is a selThe Behavior Rating Inventory of Executive Function Adult Version BRIEF-A;  is a staThe Clinical Global Impression-Improvement CGI-I;  providesThe Conners’ Continuous Performance Test-3 CPT-3;  is a comTo assess adherence, participants were instructed to document their daily usage of the eyeglasses . Potential side effects and adverse events were assessed by the study investigators during the follow-up assessment.t-tests were used to test the effect of the Neuro-glasses intervention, comparing the baseline and end-of-intervention performances. Normality distribution of data was assessed using the Shapiro–Wilk test. Due to the exploratory nature of the study, no corrections for multiple testing were applied. The safety analysis included all available data on the intent-to-treat (ITT) population.Paired samples Mixed model ANOVA was used to explore any potential effect of covariates such as gender, age, eyeglasses, learning disabilities, treatment naïve, and ASRS total score. None of the covariates were found significant, thus were not included in the final model.D) using a paired t-test with a 0.05 two-sided significance level. Assuming a 20% attrition rate over the course of the study, 108 participants were targeted for inclusion  = 0.12, p = 0.037]. Self-reports on the ASRS total score approached significance , showing a 4% reduction in ADHD symptoms post-intervention. No significant effect was found on the ASRS hyperactive subscale . Improvement in the BRIEF-A was evident for the Metacognitive Index . There were no significant effects for the BRIEF-A Behavior Regulation index or the Global Executive Composite .t (92) = 2.25, p = 0.027) and reduced incorrect responses to non-targets  = 2.92, p = 0.004). All other CPT-3 measures were less sensitive to intervention-based changes in performance . Sixty-two percent of the participants met the response criteria, having much or very much symptomatic improvement after using the Neuro-glasses.No significant covariate effect was observed for demographic or baseline parameters such as gender, age, eyeglasses, learning disabilities, treatment naïve, and ASRS total score.This study provides preliminary support for the safety and efficacy of a peripheral visual stimulation-based device in managing ADHD in adults. Reduction in ADHD symptoms was demonstrated by the ASRS inattentive subscale, reflecting the rated adult’s difficulty in maintaining attention for long periods, organizing/planning, paying attention to details, and committing reckless mistakes . No signDespite the small effect sizes, the results are encouraging, given that the level of ADHD symptom manifestation in the study population was relatively mild, as reflected by the average ASRS baseline score. The clinical meaningfulness of the findings is further supported by the 62% of participants who positively responded to the intervention, as assessed by the CGI-I.Assessment of the intervention adherence rate revealed that most participants (63%) wore the Neuro-glasses for at least 4 hours daily, whereas only 7% reported wearing the Neuro-glasses occasionally for up to 2 hours daily. These findings, together with the relatively low dropout rate (<10%), are of high importance, as they indicate that the intervention was well tolerated and accepted by ADHD adults. Moreover, the high adherence rate suggests that the effect of the Neuro-glasses is notable and meaningful for the user.The current pilot study confirms that the Neuro-glasses hold minimal risks, as no clinically significant adverse events were associated with the intervention. Reports involved minor events of headache, dizziness, and eyestrain that were all transient, relatively mild and had not resulted in any discontinuations of the intervention.The etiology of ADHD is related to various genetic and environmental factors . Though The Neuro-glasses presumably attenuate ADHD symptoms by stimulating the visual periphery. However, it is still unclear what is the mechanism underlying their effect. A possible explanation is that the Neuro-glasses might operate via the arousal system. Arousal is crucial for survival, as it regulates consciousness, attention, alertness, motivation, and information processing. Arousal regulation reflects the competence of the brain to deal with ongoing situational demands. Its dysregulation has been linked to psychiatric and physiological disorders and cognitive impairments . RelevanWhile the Neuro-glasses are not an optical device by definition, they may operate via visual correction. A large body of evidence associates ADHD and problems of vision . ADHD paWhile the results of this study are encouraging, we acknowledge certain important limitations. First, this is an uncontrolled study. Thus, we cannot rule out the contribution of placebo effects. Second, given the exploratory nature of the study, no primary endpoint was predetermined. Third, the current study population does not represent the high prevalence of comorbidities in the ADHD population and their effect on attention symptoms since ADHD adults having any psychiatric or neurological comorbidity were excluded from the study. Fourth, this study does not control for the possible confounding effects of visual problems and emotional or motivational factors that may affect the conclusive assessment of improvement. Fifth, due to the study design, it is essential to recognize that with regards to the CPT specifically, we cannot rule out a possible acute impact of wearing the Neuro-glasses, as opposed to effects caused by their regular use.To conclude, Neuro-glasses provide a non-pharmacologically safe approach to managing ADHD in adults. These preliminary encouraging findings merit further research including future controlled studies evaluating the efficacy of a peripheral visual stimulation-based intervention in adults and possibly children with ADHD. Moreover, the current study provides important insights into the utility of visual stimulation as an intervention for treating ADHD and potentially for additional psychiatric and neurological disorders involving dysregulation of arousal levels.The original data collected in the study is included in the article. Further inquiries can be directed to the corresponding author.The studies involving humans were approved by Max Stern Yezreel Valley College Institutional Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.YR: Conceptualization, Methodology, Project administration, Resources, Supervision, Writing – original draft. CG: Conceptualization, Investigation, Writing – review & editing. GV: Conceptualization, Investigation, Writing – review & editing. CB-M: Data curation, Formal analysis, Methodology, Project administration, Writing – review & editing. DG: Conceptualization, Data curation, Methodology, Software, Writing – review & editing. NM-K: Supervision, Writing – original draft. ZE: Conceptualization, Investigation, Supervision, Writing – review & editing.


Complex burns are highly morbid injuries that can cause severe disfigurement and can be devastating to one’s quality of life and psychosocial well-being. Currently, there are no simple, single-stage procedures available for extensive or multifocal burns to address full-thickness trilaminar defects. Our team has previously demonstrated the viability of an adipose-first reconstruction to address hypodermal defects. In this study, we demonstrate the efficacy of a combined adipose plus finely minced skin to achieve a single-stage trilaminar skin reconstruction.Full-thickness burns were created on female Yorkshire swine. After 48-hours, escharectomies were performed to the level of fascia. The wounds were layered with adipose harvested from female Yorkshire swine. In one group, autologous split-thickness skin grafts were cut into pixel size (0.3x0.3 mm) grafts and layered on top of the adipose. Pigs were maintained for 4-weeks with weekly photography, ultrasound, followed by endpoint histology and tension measurements.At the end of the 4-week period, adipose combined with pixel graft demonstrated improved epithelialization and less contracture (p< 0.01). Thickness and mobility measurements were consistent in both groups. This findings were similar to our previous approaches using adipose following surgical debridement. Tissue pliability in the pixel grafting group was maintained to a high degree. Cross sections were performed which showed the persistence of fat graft at the base of the wounds.Immediate, single-stage trilaminar reconstruction of full-thickness complex burns reduces contracture, mitigates adhesion, and restores normal soft-tissue thickness, therefore, presenting a paradigm changing approach in the current practice of burn injuries to the mobile surfaces.Our results support the therapeutic potential of adipose-based soft-tissue reconstruction of burns to both enhance hypodermal augmentation and mitigate fibrotic complications including contracture and adhesions. Our data suggest that this approach is compatible with the standard of care skin grafting, and in fact provides improved epidermal thickness and pliability.


Rapid treatment is critical in managing acute ischemic stroke (AIS) to improve patient outcomes. Various strategies have been used to optimize this treatment process, including the Acute Stroke Protocol (ASP) activation, and minimizing the duration of key performance metrices, such as door-to-needle time (DNT), CT-to-needle time (CTNT), CT-to-groin puncture time (CTGP), and door-to-groin puncture time (DGPT). However, identifying the delay-causing sub-tasks within the ASP could yield novel insights, facilitating optimization strategies for the AIS treatment process.This two-phase prospective observational time and motion study aimed to identify sub-tasks and compare their respective durations involved in the treatment process for AIS patients within ASPs. The study compared sub-task durations between “routine working hours” and “evenings and weekends” (after-hours), as well as between stroke neurologists and non-stroke neurologists. Additionally, the established performance metrices of AIS were compared among the aforementioned groups.P < 0.05) were observed when were performed by a non-stroke neurologist and during after-hours operations. Furthermore, certain sub-tasks were exclusively performed during after-hours or when the treatment was provided by a non-stroke neurologist. Consequently, DNT, CTNT, and CTGP were significantly prolonged for both non-stroke neurologists and off-hours treatment. DGPT was significantly longer only when the ASP was conducted by non-stroke neurologists.Phase 1 identified and categorized 34 sub-tasks into five broad categories, while Phase 2 analyzed the ASP for 389 patients. Among the 185 patients included in the study, 57 received revascularization treatment, with 30 receiving intravenous (IV) thrombolysis only, 20 receiving endovascular thrombectomy (EVT) only, and 7 receiving both IV thrombolysis and EVT. Significant delays were observed in sub-tasks including triage, registration, patient history sharing, treatment decisions, preparation of patients, preparation of thrombolytic agents, and angiosuite preparation. The majority of these significant delays (The study identified several sub-tasks that lead to significant delays during the execution of the ASP. These findings provide a premise to design targeted quality improvement interventions to optimize the ASP for these specific delay-causing sub-tasks, particularly for non-stroke neurologists and after-hours. This approach has the potential to significantly enhance the efficiency of the AIS treatment process. Providing rapid and efficient treatment is crucial for managing acute ischemic stroke (AIS) and improving patient outcomes. Quality improvement studies in AIS have focused on identifying, establishing, and improving key process indices, including door-to-CT (DTCT), door-to-needle time (DNT), CT-to-needle time (CTNT), CT-to-groin puncture time (CTGP), and door-to-groin puncture time (DGPT) –9. TheseA novel approach could be to break-down the AIS treatment process into smaller steps, which we will refer to as “sub-tasks”. In healthcare, no formal definition for “sub-tasks” exists, but they can be seen as small, specific actions or components within a larger task or process. These sub-tasks contribute to the overall completion of the task and can be identified, measured, and optimized to make the process more efficient. Within the context of the AIS treatment process, key tasks that is used in studies aimed to lower treatment times include DTCT, CTNT, and CTGP times. These tasks can then be broken down into smaller tasks (sub-tasks) such as patient triage, registration, blood sample collection, sharing medical history, neurological evaluation, and transport to the radiology department, among others. The approach of identifying sub-tasks and quantifying their durations, followed by the identification of sub-tasks resulting in delays may provide valuable insights into the AIS treatment process, which may inform new improvement strategies and ultimately lead to better patient outcomes.Observational “time and motion study” is a method from industrial engineering that may aid in identifying and documenting sub-tasks and their durations. This method involves observing and measuring tasks within a process using a stopwatch to establish the corresponding times for the sub-tasks. Observational time and motion studies have previously been utilized to enhance overall emergency department (ED) workflow and minimize wait times –18. HoweThe objectives of this study encompassed three main aspects. Firstly, it aimed to identify sub-tasks involved in the AIS treatment process. Secondly, it measured and recorded the durations of these sub-tasks to further determine potential sub-tasks causing treatment delays. This objective involved comparing sub-task durations between “routine working hours” and “evenings and weekends” (after-hours), as well as between stroke neurologists and non-stroke neurologists. Finally, the study aimed to assess the impact of these delay-causing sub-tasks on key process metrices of the ASP process, such as DNT and DGPT, among the abovementioned groups.A two-phase prospective observational time and motion study was undertaken to evaluate the AIS treatment process. The research protocol of this study received an exemption from the Nova Scotia Health Authority Research Ethical Board due to its focus on quality improvement. Instead, the study was approved by the Nova Scotia Health Authority Quality Improvement and Safety Council. Since the study was a quality improvement initiative and did not collect patient-level data, consent was not required from patients or their next of kin, either in written or verbal form.The study was conducted in the Emergency Department (ED) at the Queen Elizabeth II Health Science Center (QEII) in Halifax, Nova Scotia (NS), Canada. QEII is the only comprehensive stroke center in the province of Nova Scotia. This hospital offers intravenous (IV) thrombolysis treatment to patients within its catchment area and provides endovascular thrombectomy (EVT) treatment to patients residing in the provinces of NS and Prince Edward Island (PE). Both NS and PE are relatively small in terms of area and population, with NS having a population of one million and PEI having a population of 173,000. QEII is a large urban tertiary care teaching hospital. The center was staffed with two stroke neurologists and 19 non-stroke neurologists during the study period, and has 24/7 on-site CT (computed tomography) services, along with interventional neuroradiologists.The study focused on adult patients who were presented at the ED with an acute suspected stroke, resulting in the activation of the ASP. The study included only patients who had ASP activation before their arrival. Patients who had an in-hospital stroke and those who arrived within 10 min of pre-notification were not eligible. These exclusions were due to the unavailability of the on-site observer, who had to reach the location after receiving the pre-notification. The patient population encompassed those with ischemic stroke, hemorrhagic stroke, transient ischemic attack (TIA), or stroke mimic.The AIS treatment process begins with the ASP activation by either the attending neurologist or the ED charge physician, either before or after the patient's ED arrival. A multidisciplinary stroke team, including a neurologist, neurology resident, stroke nurse (during routine hours), CT technician, and radiologist/radiology resident, is notified during this pre-notification period using a pager notification system. In the ED triage area, the patient is assessed by the ED nurse, neurologist, and neurology resident. Neurological examination, National Institutes of Health Stroke Score (NIHSS) assessment, and data collection from paramedics ensue.The patient is then transported to the CT Scanner for brain imaging, starting with a plain CT head potentially followed by CT angiography (CTA), and CT perfusion (CTP). After imaging, patients may be further evaluated in the Diagnostic Radiology Department or the ED, depending on the neurologist's decision. Upon AIS confirmation, eligibility for IV thrombolysis and EVT is determined. While consent may be sought, emergency consent is typically applicable per Canadian guidelines. Treatment pathways vary based on IV thrombolysis, EVT, or both, and the time of day. During routine hours, IV thrombolysis occurs in the Radiology Department, while EVT patients await their turn in the Interventional Radiology Department angiosuite. After hours, patients return to the ED for IV thrombolysis and then proceed to the angiosuite for EVT, unless urgent issues necessitate ED treatment.All patients were observed between 7 am and 11 pm, with “routine working hours” observations conducted on weekdays from 8 am to 4 pm, and all other observations considered during “after-hours”. The rationale for considering the observation time from 7 am to 11 pm stemmed from the limited availability of the only observer, who meticulously documented the execution of each ASP.In phase 1 of this study, conducted from November 1, 2021 to November 16, 2021, a single observer closely observed the AIS treatment process carried out by the stroke team. The observer, GK, is a Ph.D. candidate affiliated with a healthcare optimization laboratory dedicated to enhancing AIS treatment delivery. The observer aimed primarily to identify and document the sub-tasks within the AIS treatment process. Sub-tasks were identified based on reviews and opinions of stroke experts. Initially, five major tasks of the treatment process were defined based on the current literature: (1) Arrival to Imaging (Prior to Imaging), (2) Image Acquisition, (3) Treatment Decision, (4) Preparations for Thrombolysis, and (5) Preparation for EVT.“Arrival to imaging” included the temporal duration from the suspected AIS patient's arrival at the ED to their transfer to the radiology department for imaging.“Image acquisition” denoted the interval commencing upon arrival at the radiology department and culminating in the acquisition of CT imaging.“Treatment decision” included the temporal duration between the acquisition of CT imaging and the determination to initiate thrombolytic therapy, based on CT imaging and AIS treatment guidelines.“Preparations for thrombolysis” referred to the duration extending from the treatment decision to the actual administration of thrombolytic therapy.“Preparation for EVT” signified the time elapsed from the administration of thrombolytic therapy to the initiation of groin puncture for the purpose of performing EVT.Finally, in this phase of our study, sub-tasks carried out to complete each of these major tasks were meticulously identified and documented, relying upon the reviews and insights of stroke experts.During the second observation phase—November 17, 2021 to June 15, 2022, the ASP workflow was closely monitored by the same observer to document all sub-tasks and their relevant information on a standard treatment process report form. The observer shadowed the workflow and recorded the following variables:Mode of arrival: whether the patient arrived using EMS or as a walk-in.Type of neurologist: if the ASP was conducted by a stroke neurologist or a non-stroke neurologist.Time of day: whether the patient arrived during routine working hours or after-hours.Diagnosis: determined after CT image acquisition, categorized as AIS, hemorrhage, stroke mimic, or unknown.Treatment types: whether the patient received IV thrombolysis, EVT or both.Start and end times of each sub-task: recorded for each suspected AIS patient.If any new sub-tasks were observed during this phase, they were documented and recorded, along with any interruptions.The outcome of the phase 1 study involved the identification and documentation of all the sub-tasks necessary to complete each major task within the ASP. The phase 2 study outcomes included differences in median durations of sub-tasks, comparing routine working hours with after-hours and stroke neurologists with non-stroke neurologists. Additionally, the study outcomes for the key process metrices of the ASP included differences in median durations of process metrices, including DTCT, CTNT, CTGP, DNT, and DTGP times.Descriptive statistics were used to describe the baseline characteristics of the participants. Also, the baseline characteristics were compared between routine working hours and after-hours as well as between non-stroke neurologists and stroke neurologists, and the Chi-Square test was employed to analyze these categorical variables. Further, for each sub-task, the median duration and Interquartile Range (IQR) were calculated, and comparisons were made between the aforementioned groups using the Mann-Whitney U Test. Finally, the study also calculated the median DTCT, CTNT, CTGP, DNT, and DTGP time, with comparisons made between the above-mentioned groups using the Mann-Whitney U Test. These final comparisons were carried out to gain a comprehensive understanding of the effects of sub-tasks on the key process metrices of the ASP. The statistical analyses were conducted using Minitab version 21 .Arrival to Imaging (Prior to Imaging), Image Acquisition, Treatment Decision, Preparations for Thrombolysis, and Preparation for EVT. We further classified the sub-tasks within each category based on their order of occurrence and location. In addition to the sub-tasks identified during Phase 1, some were also observed during Phase 2, resulting in a total of 34 sub-tasks related to ASP being recorded at the study center. Some sub-tasks were merged due to patient-related reasons, hospital staff-related factors, or study center-related constraints. This combining of sub-tasks was considered beneficial for assessment and comparison purposes.During the phase 1 observational study, we identified the sub-tasks involved in the ASP guiding the treatment of AIS. Our observations led us to categorize the steps during ASP flow into five primary steps: A total of 389 patients with suspected AIS and an ASP activation were assessed. Amongst them, 204 (52.4%) were excluded due to various reasons as mentioned in Out of the 120 patients diagnosed with stroke, 93 (77.5%) had AIS, 14 (11.7%) had TIAs, and 13 (10.8%) had hemorrhagic strokes. Out of the 65 patients who did not have a stroke diagnosis, 3 (4.6%) were diagnosed with migraine, 5 (7.7%) were diagnosed with seizure, and 57 (87.7%) had an unclear diagnosis even after CT imaging; they were subsequently transferred to the ED for further assessment. Of the 93 patients diagnosed with ischemic stroke, 57 (61.3%) received treatment at the study center. The treatment modalities were distributed as follows among the treated patients: IV thrombolysis only , EVT only , and both IV thrombolysis and EVT .Additional information regarding the baseline characteristics of the observed patients and their treatment process, categorized based on both the time of day and the assessing neurologist, can be explored in arrival to imaging stage, it was observed that sub-tasks “triage and registration”  took significantly longer time during off-hours, while sub-tasks “sharing patient's medical history”  took longer when the attending was a non-stroke neurologist. Conversely, during the image acquisition stage, none of the sub-tasks caused delays in treatment process, regardless of the time of day or the attending neurologist.During the treatment decision stage, the sub-task “treatment decision time” took significantly longer both during off-hours  and when the ASP was carried out by a non-stroke neurologist . Further, the frequencies of sub-tasks “re-evaluation of the treatment decision,” “consent conversation,” and “laboratory results wait” were skewed toward non-stroke neurologists , and it was observed that stroke neurologists typically do not perform these sub-tasks. However, these sub-tasks did not reach a statistical significance due to them being performed in small numbers by stroke neurologists.During the preparations for thrombolysis stage, the sub-task “preparing patient and mixing thrombolytic agent” took significantly longer both during off-hours  and when the attending was a non-stroke neurologist . Further, the sub-task “ED room arrangement” was exclusively observed during non-stroke neurologist treatment, and the majority (88.9%) of these arrangements occurred after-hours. Again, statistical significance cannot be established for this sub-task due to skewed distribution of the frequencies among the groups.During the preparations for EVT stage, the sub-task “preparing angiosuite” took significantly longer both during off-hours  and when the attending was a non-stroke neurologist .During the U = 61.5; P < 0.001; Z = −3.33), DNT , and CTGP time  were significantly longer during after-hours. Similarly, CTNT , DNT , CTGP time , and DTGP time  were significantly longer when a non-stroke neurologist carried out the ASP. In this study, the median times for overall key process metrices of the ASP process were determined. The median DTCT time was 14 min , CTNT was 24 min , DNT was 37 min , CTGP time was 61.5 min , and DTGP time was 74 min . Further, group-wise comparisons of these process metrices were performed. For the routine working hours vs. after-hours comparisons, CTNT (median time in minutes, 15 vs. 27; This study shows that applying an observational time and motion study to first identify and then quantify tasks has value in recognizing areas for improvement to reduce treatment time for AIS patients. Time and motion studies have been used in emergency departments to better understand workflow , 19–21; sub-task in a single center, which is likely the most appropriate level to evaluate processes using time and motion studies. Each center often develops its own unique processes that are difficult to generalize across various centers. Therefore, the use of time and motion studies to identify areas for improvement can be extended to other individual centers, including smaller community and rural hospitals, which present distinct challenges, particularly concerning on-site resources and the need for tele-stroke services to make treatment decisions (This study identified and quantified each specific task or ecisions .The results of this time and motion study showed that the study center had significant delays during off-hours. Poor patient outcomes , 24 and Additionally, this time and motion study revealed that non-stroke neurologists performed additional non-value-added tasks and took longer task completion times in comparison to their stroke-trained colleagues. Specifically, non-stroke neurologists took longer in obtaining patient history and making treatment decisions. Further, specific sub-tasks, such as the re-evaluation of the treatment decision, consent conversation, laboratory results wait, and ED room arrangement, were either exclusively conducted or disproportionately performed by non-stroke neurologists, resulting in extended treatment times. This result is important, as there are currently very few studies that show that stroke trained neurologists perform more efficiently in the treatment of AIS patients. Challenges in the recruitment and retention of stroke neurology workforce has been identified , which iWe believe that our study provides a frontier for future research aimed at improving the ASP process. Using our methodology as a foundation, stroke centers may identify their specific set of delay-causing sub-tasks at their respective facilities. Comprehensive stroke centers may utilize our approach to identify delay-causing sub-tasks in both IV thrombolysis and EVT treatment processes while primary stroke centers may focus on identifying optimization targets for IV thrombolysis at their centers. Based on their relevance and contextual conditions, potential strategies to optimize these delay-causing sub-tasks might include training sessions for efficient sub-task execution, parallel execution, or even considering the omission of certain non-value-adding sub-tasks.Some limitations should be taken into consideration when interpreting the results of the current study. Firstly, it was not feasible to observe all patients arriving with an ASP activation, and the observations were limited to patients with an ETA exceeding 10 min. Additionally, the sample size was relatively small, which affected the observations for some sub-tasks that were recorded in low frequencies. Furthermore, the observations were limited to a specific time frame, from 7 am to 11 pm, and therefore, the sub-tasks identified in this study are limited to activities that occurred during the observation time frame. Finally, the study was conducted during the COVID-19 pandemic, which imposed health regulations and restrictions that may have slightly affected the AIS treatment process.The aim of the current study was to identify the sub-tasks that are associated with AIS treatment and determine their impact on the overall ASP process. The study center recorded several sub-tasks related to ASP, highlighting the complexity of the ASP process. During phase 2, the study identified multiple individual or combined sub-tasks that caused delays in the treatment process, both when a non-stroke neurologist was involved or when the ASP was carried out after-hours. Moreover, the study identified several sub-tasks that were exclusively performed during specific treatment situations. These delay-causing sub-tasks resulted in longer CTNT, DNT, and CTGP time for both non-stroke neurologists and after-hours ASPs. Furthermore, when a non-stroke neurologist conducted the ASP, the DTGP time was longer.The study provides valuable insights into the sub-tasks associated with AIS treatment and their impact on the overall ASP process. Although there are some limitations, our study offers a distinctive approach by identifying areas of concern and subsequently designing targeted quality improvement interventions that could cater to the unique challenges of individual stroke centers. Further research is required to validate the findings in different settings and establish a foundation for the generalizability of targeted interventions aimed at reducing treatment delays.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Nova Scotia Health Authority Quality Improvement and Safety Council. Written informed consent from the patients OR patients legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.GK: study design, data collection, data analysis, preparation of figures and tables, and preparation of drafts of manuscript. MK: data analysis, preparation of figures and tables, and preparation of drafts of manuscript. NK: study design, editing, formatting, funding the project, supervising the work, and revision of manuscript for intellectual content. GG: input to study design and revision of manuscript for intellectual content. All authors contributed to the article and approved the submitted version.


Endovascular embolization (EE) has been used for the treatment of blood vessel abnormalities, including aneurysms, AVMs, tumors, etc. The aim of this process is to occlude the affected vessel using biocompatible embolic agents. Two types of embolic agents, solid and liquid, are used for endovascular embolization. Liquid embolic agents are usually injectable and delivered into the vascular malformation sites using a catheter guided by X-ray imaging . After injection, the liquid embolic agent transforms into a solid implant in situ based on a variety of mechanisms, including polymerization, precipitation, and cross-linking, through ionic or thermal process. Until now, several polymers have been designed successfully for the development of liquid embolic agents. Both natural and synthetic polymers have been used for this purpose. In this review, we discuss embolization procedures with liquid embolic agents in different clinical applications, as well as in pre-clinical research studies. Endovascular embolization (EE) is a minimally invasive surgical procedure for the treatment of blood vessel abnormalities in various regions of the body. Endovascular treatment decreases hospitalization time and speeds up recovery as compared to open surgery . EE can Liquid embolic agents are usually injectable and delivered into the vascular malformation sites using a catheter guided by X-ray imaging . After the injection, the liquid embolic agents transform into a solid implant in situ, based on a variety of mechanisms, including polymerization, precipitation, and cross-linking, through ionic or thermal processes . The bioEmbolic materials are classified into solid embolic agents or liquid embolic agents. Solid embolic agents include metal coils and plugs, which are mostly used for the treatment of focal vascular abnormalities . StudiesHigh-flow vascular malformations occur when blood flows from a feeding artery directly to a draining vein, bypassing the capillary bed . BecauseThe goal of endovascular embolization of AVMs is the closure of the whole nidus without occluding other surrounding normal and important vessels ,13. AlthAVFs remain challenging when embolization is not accompanied by resection in that their high-flow nature may cause embolic materials to migrate into the distal draining veins, potentially resulting in unintentional pulmonary embolization ,12. SimiHypervascular tumors consist of abnormally large numbers of blood vessels feeding into or contained within the tumor . These tAneurysms are dilatations or bulges caused in weakened vessel walls, which can rupture and cause internal bleeding if the tension on the weakened wall increases . AneurysThe most common complications after endovascular aneurysm repair are type I and type II endoleaks, characterized by the persistent perfusion within the aneurysmal sac. Type I endoleaks result from an inadequate seal and can be seen either at the proximal end of the graft (type Ia) or at the distal end of the graft (type Ib) . The occIn general, liquid embolic agents can be classified in two categories: polymerizing liquid embolics and precipitating liquid embolics. In the case of polymerizing liquid embolics, monomer or prepolymer solutions polymerize in the presence of an initiator  into a covalently crosslinked solid material. Polymerizing liquid embolics also include several in situ gelling systems which are thermo-responsive and undergo sol-to-gel phase transition at body temperature. For the precipitating embolics, a solution of preformed polymer in a water-miscible solvent is injected in the body. After injection, the solvent diffuses out and the embolic material precipitates into a solid matrix. The use of cyanoacrylate (CA) glues for polymerization in the presence of blood was proposed in the 1970s . N-butylNBCA monomer is a clear liquid which polymerizes to an adhesive, nonbiodegradable rigid material upon activation by contact with any ionic substances  ,28 via aNBCA is not radiopaque, so it is opacified by mixing ethiodol, tantalum, or tungsten powder to monitor its flow during injection . In ordeResearchers have worked with NBCA for decades as an embolic agent. In two early studies, reported in 1978 and 1981, NCBA was reported to be successfully used for the occlusion of the renal artery of dog ,39 and rIn 2005, Denys et al. used NBCA for the preoperative embolization of portal vein for partial hepatectomy in patients . Later, Fibrin is a protein polymer formed from the catalytic action of thrombin on fibrinogen . Fibrin In 1999, Nagino et al. reported a study on 16 patients who underwent preoperative right trisegment portal vein embolization with fibrin glue (Beriplast) for right hepatic trisegmentectomy without any complications . In the Copolymers of poly(N-isopropyl acrylamide) (NIPAAm) are a waterborne in situ gelling polymer system that can be used for endovascular embolization. Although poly(NIPAAm) itself is non-degradable, NIPAAm-based copolymers are ideal as embolic agents as they can be functionalized into degradable  and radiIn 1996, Matsumaru et al. investigated a NIPAAm-based copolymer, poly(N-isopropylacrylamide-co-N-n-propylacrylamide), as an embolic agent for intravascular neurosurgery . This maIn 2006, Lee et al. synthesized a NIPAAm-based copolymer poly(NIPAAm-co-HEMA-acrylate) which was mixed stoichiometrically with pentaerythritol tetrakis 3-mercaptopropionate (QT) in 0.1 N PBS solution at pH 7.4 to form a physical–chemical hydrogel  via MichIn 2009, Dai et al. developed thermoresponsive BAB-type HEMA/NIPAAm triblock copolymers . At higher temperatures, the aqueous solution of BAB copolymers containing shorter PNIPAAm blocks (BAB1-6) failed to form a stable gel. On the other hand, a relatively stable gel was achieved with BAB copolymers, having longer PNIPAAm blocks (BAB1-8) . FurtherIn 2011, Zhao et al. explored a NIPAAm-based copolymer p(N-isopropylacrylamide-co-butyl methylacrylate) (PIB) nanogel, mixed with iohexol (PIB-I-6150), as a novel blood-vessel-embolic material in the transcatheter arterial embolization (TAE) therapy of liver tumors. Their performance was compared with those of Lipiodol and PVA particles  . The in In 2012, Bearat et al. reported a comparative study of the properties between a pair of NIPAAm-based simultaneously physically and chemically gelling polymer systems. The synthesized polymer gelling systems includes poly(NIPAAm-co-cysteamine) with poly(NIPAAm-co-HEMA-acrylate) (NC-NHA) and poly(NIPAAm-co-cysteamine) with poly(NIPAAm-cysteamine-co-vinylsulfone) (NC-NCVS). Some differences were noted in terms of the rheological and kinetic studies . The NC–Vernon et al. developed a novel liquid embolic polymerizing system using poly(propylene glycol) diacrylate (PPODA) and pentaerythritol tetrakis (3-mercaptopropionate) (QT) for the occlusion of AVMs . Both PPIn 2010, Riley et al. investigated this PPODA-QT-based in situ gelling system formulated with injectable contrast agents for intracranial aneurysm embolization . For thiIn a study performed in 2013, Soodak et al. developed a poly(ethylene glycol) diacrylate (PEGDA)-QT gelling system using PEGDA of different molecular weights (PEGDA575 and PEGDA700), and investigated their characteristics in . Data inShear-thinning biomaterials were developed through collaborations with the Mayo Clinic, Harvard-MIT . These nTheratarget produces a silk elastin hydrogel with low viscosity. This polymer system is designed to treat hypervascular tumors that are unresponsive to systematic chemotherapy. The polymeric treatment is delivered in a transcatheter arterial chemoembolization (TACE) procedure. This silk-elastin-like protein polymer (SELP) is part of an injectable liquid-to-solid transformation used for the treatment of hypervascular tumors. The system provides localized delivery of chemotherapeutics to deep penetration and occlusion of the surrounding feeding vasculature. The low-viscosity chemoembolic system is also compatible with many smaller-gage catheters for access to targeted vessels . Silk elThe Instylla Hydrogel System is used for the embolization of tumors and organs with a hydrophilic hydrogel derived from functionalized glycol capable of rapid formation ,93,94. UAn initial report investigating the use of calcium alginate (CA) as an endovascular liquid embolic was provided by Becker et al. in 2001 . By 2002Around the same time, other groups were also investigating alginate for endovascular embolization. In 2003, Raymond et al. explored the potential use of alginate for endovascular treatment of aneurysm while providing simultaneous drug delivery of platelet-derived growth factor-BB (PDGF-BB) or transforming growth factor-β1 (TGF-β1) . In thisBy 2005, Becker et al. reported a longer-term swine RM model . In 8 ofIn 2007, Becker et al. conducted a preliminary study to use CA as an embolic agent in a swine side-wall aneurysm model . In 10 aIn a more recent study in 2020, Fan et al. investigated an injectable and radiopaque liquid metal  and Indium (In))/calcium alginate hydrogel for endovascular embolization and tumor embolotherapy . LM drop® (marketed by Evonik) has been used as a coating material for orally administered tablets since 1954 [Eudragitnce 1954 , which hnce 1954 ,103. Eudnce 1954 . Inside nce 1954 . In 1998nce 1954 . For thince 1954 . After ence 1954 . During Although Eudragit-E has been used for endovascular embolization of brain AVMs for some time, it is currently not widely used because of safety and feasibility. The 10% Eudragit-E mixture is not supplied in ready-to-use vials and its use needs to be approved by an Institutional Review Board as well as prior informed consent from patients and their family . AccordiSquid and Squid Peri  are non-adhesive, precipitating liquid embolic agents composed of ethylene vinyl alcohol copolymer (EVOH) in dimethyl sulfoxide (DMSO) solvent with suspended micronized Tantalum powder for radiopacity . Squid aSquid has been used as a liquid embolic agent for AVM, AV fistulas, and tumors. In 2014, Akmangit et al. reported a study with 28 patients with AVMs and AV fistula, who were treated with Squid 18 and Squid 12 . No techOnyx (Medtronic Inc.) is a poly (EVA) copolymer-based liquid embolic system which is dissolved in DMSO ,82. Onyx−1 [Onyx is marketed in different formulations, including Onyx 18, Onyx 34, and Onyx 500, with viscosities of 18 mPa s, 34 mPa s, and 500 mPa s, respectively . Low-vis−1 . Additio−1 ,123.® has been used successfully for the treatment of cerebral AVMs [In 1990, Taki et al. developed an EVA-based embolic agent which was clinically applied in three cases of AVM embolization successfully . Since tral AVMs ,127,128,ral AVMs ,131,132,ral AVMs ,133,134,ral AVMs ,135,136,ral AVMs , bleedinral AVMs ,139, endral AVMs ,149,150,ral AVMs ,152,153.Onyx has been widely used in the treatment of cerebral AVMs. In 2011, Xu et al. reported their experiences in the treatment of brain AVMs with Onyx embolization on 86 patients . They coIn 2004, Numan et al. reported endovascular transcatheter embolization of congenital peripheral VMs in nine patients, concluding that Onyx is a promising embolic agent and advantageous over conventional embolic agents . In 2017In 2010, Wang et al. reported the endovascular embolization of congenital brain arteriovenous fistulas (BAVF) with a combination of Onyx and detachable coils/balloon-assisted coils in 15 patients . After tIn 2005, Weber et al. reported the treatment of 22 unruptured wide-necked intracranial aneurysms with Onyx-500, resulting in a 91% occlusion rate without permanent severe morbidity and mortality . In 2015In 2003, Lupattelli et al. reported the successful Onyx embolization of a renal artery aneurysm, where complete exclusion was achieved immediately without any distal embolization or intra-aneurysmal flow . In 2007In 2010, Jaratua et al. reported Onyx embolization in a patient for the treatment of ruptured splenic artery aneurysm where complete embolization of the aneurysm and the stoppage of the active bleeding was observed . In the Onyx has been used as a monotherapy for the treatment of type II endoleaks since 2001 . In 2001Onyx has been widely used for the treatment of type II endoleaks, but there are a few reports of its use in type I endoleaks. In 2010, Grisafi et al. reported a successful Onyx embolization of a type I endoleak in one patient who declined the option for surgical repair . In 2011Onyx has been widely used for preoperative endovascular embolization. In 2008, Gore et al. published a review of preoperative embolization of cranial and spinal tumors using Onyx, performed over a 19-month period on 10 patients, and concluded Onyx to be advantageous due to its deep penetration ability, causing extensive tumor infarction, embolizing extensive portions of the tumors, and the safety of catheter withdrawal after the process . In 2012In some cases, Onyx embolization was performed for the management of hemoptysis. In 2010, Khalil et al. shared their preliminary experience of systemic arterial embolization with Onyx in 15 patients with hemoptysis, where it was controlled in 14 cases . In 2021Several comparative clinical studies between Onyx and NBCA were reported to investigate the superior efficacy of these materials for embolization. In 2010, Loh et al. reported a randomized trial of Onyx and NBCA for embolization of cerebral AVMs in 117 patients . In totaPHIL™  is a non-adhesive liquid embolic agent comprised of a biocompatible copolymer, poly(lactide-co-glycolide), and poly(hydroxyethyl methacrylate) (PHEMA), covalently bonded to an iodine component for radiopacity and dissolved in DMSO ,159. It PHIL produces faster plug formation, which may decrease procedure time . It alsoIn 2017, Vollherbst et al. performed a comparative study between ONYX and PHIL where an in vitro AVM model was embolized with these two embolic agents . The resIn 2018, Varadharajan et al. presented their preliminary experience using PHIL for the endovascular embolization of vascular shunts of eleven patients who had experienced satisfactory embolization results without recanalization for 6 months . The autAs early as 2006, iodine-containing polyvinyl alcohol systems have been investigated as liquid embolics for EE. Dudeck et al. evaluated the use of intrinsically radiopaque iodine containing polyvinyl alcohol as a liquid embolic in a swine model of side-wall, wide-neck aneurysms ,169. In This review article has discussed liquid embolic agents used for transcatheter endovascular embolization. A few liquid embolic agents, such as Eudragit-E, are currently no longer being used due to safety and feasibility issues. At present, a few precipitating liquid embolic agents, such as Onyx and Phil, are widely used for the purpose of endovascular embolization. Researchers are working to develop alternatives to these embolic agents, which are delivered with the undesirable, toxic DMSO solvent that can cause significant inflammatory response in patients. Furthermore, newer liquid embolic materials do not require toxic solvents such as DMSO which require special catheters for delivery. Therefore, several in situ gelling-type liquid embolic systems are being engineered and developed. Successful in vivo and pre-clinical studies show the promising future of these liquid embolic systems for endovascular embolization. These newer materials are also designed to be biocompatible with fewer imaging artifacts as compared to Onyx, and excitingly targeted to influence and allow regrowth of the endothelium over the aneurysmal orifice.