Cardiac arrest: An interdisciplinary scoping review of clinical literature from 2020.

Objectives: The Interdisciplinary Cardiac Arrest Research Review (ICARE) group was formed in 2018 to conduct an annual search of peer-reviewed literature relevant to cardiac arrest. Now in its third year, the goals of the review are to highlight annual updates in the interdisciplinary world of clinical cardiac arrest research with a focus on clinically relevant and impactful clinical and population-level studies from 2020. Methods: A search of PubMed using keywords related to clinical research in cardiac arrest was conducted. Titles and abstracts were screened for relevance and sorted into 7 categories: Epidemiology & Public Health Initiatives; Prehospital Resuscitation, Technology & Care; In-Hospital Resuscitation & Post-Arrest Care; Prognostication & Outcomes; Pediatrics; Interdisciplinary Guidelines & Reviews; and a new section dedicated to the coronavirus disease 2019 (COVID-19) pandemic. Screened manuscripts underwent standardized scoring of methodological quality and impact on the respective fields by reviewer teams lead by a subject matter expert editor. Articles scoring higher than 99 percentiles by category were selected for full critique. Systematic differences between editors' and reviewers' scores were assessed using Wilcoxon signed-rank test. Results: A total of 3594 articles were identified on initial search; of these, 1026 were scored after screening for relevance and deduplication, and 51 underwent full critique. The leading category was Prehospital Resuscitation, Technology & Care representing 35% (18/51) of fully reviewed articles. Four COVID-19 related articles were included for formal review that was attributed to a relative lack of high-quality data concerning cardiac arrest and COVID-19 specifically by the end of the 2020 calendar year. No significant differences between editor and reviewer scoring were found among review articles (P = 0.697). Among original research articles, section editors scored a median 1 point (interquartile range, 0-3; P < 0.01) less than reviewers. Conclusions: Several clinically relevant studies have added to the evidence base for the management of cardiac arrest patients including methods for prognostication of neurologic outcome following arrest, airway management strategy, timing of coronary intervention, and methods to improve expeditious performance of key components of resuscitation such as chest compressions in adults and children.

Regulation of Abro1/KIAA0157 during myocardial infarction and cell death reveals a novel cardioprotective mechanism for Lys63-specific deubiquitination.

Abro1 (also known as KIAA0157) is a scaffold protein that recruits polypeptides to assemble the BRISC (BRCC36-containing isopeptidase complex) deubiquitinating (DUB) enzyme. The four subunits of BRISC enzyme include Abro1, NBA1, BRE, and BRCC36 proteins. The DUB activity of the BRISC enzyme is exclusively directed against Lys63-linked polyubiquitin that does not have a proteolytic role but regulates protein function. In this report, we identified Abro1 as a specific interactor of THAP5, a zinc finger transcription factor that is involved in G2/M control and apoptosis. Abro1 was predominantly expressed in the heart and its protein level was regulated following experimentally induced myocardial ischemia/reperfusion (MI/R) injury. Furthermore, in patients with coronary artery disease (CAD), there was a dramatic increase in Abro1 protein level in the myocardial infarction (MI) area. Increase in Abro1 leads to a significant reduction in Lys63-linked ubiquitination of specific protein targets. Reducing the Abro1 protein level exacerbated cellular damage and cell death of cardiomyocytes due to MI/R injury. Additionally, overexpression of Abro1 in a heterologous system provided significant protection against oxidative stress-induced apoptosis. In conclusion, our results demonstrate that Abro1 protein level substantially increases in myocardial injury and coronary artery disease and this up-regulation is part of a novel cardioprotective mechanism. In addition, our data suggest a potential new link between Lys63-specific ubiquitination, its modulation by the BRISC DUB enzyme, and the development and progression of heart disease.

THAP5 is a DNA-binding transcriptional repressor that is regulated in melanoma cells during DNA damage-induced cell death.

THAP5 was originally isolated as a specific interactor and substrate of the mitochondrial pro-apoptotic Omi/HtrA2 protease. It is a human zinc finger protein characterized by a restricted pattern of expression and the lack of orthologs in mouse and rat. The biological function of THAP5 is unknown but our previous studies suggest it could regulate G2/M transition in kidney cells and could be involved in human cardiomyocyte cell death associated with coronary artery disease (CAD). In this report, we expanded our studies on the properties and function of THAP5 in human melanoma cells. THAP5 was expressed in primary human melanocytes as well as in all melanoma cell lines that were tested. THAP5 protein level was significantly induced by UV irradiation or cisplatin treatment, conditions known to cause DNA damage. The induction of THAP5 correlated with a significant increase in apoptotic cell death. In addition, we show that THAP5 is a nuclear protein that could recognize and bind a specific DNA motif. THAP5 could also repress the transcription of a reporter gene in a heterologous system. Our work suggests that THAP5 is a DNA-binding protein and a transcriptional repressor. Furthermore, THAP5 has a pro-apoptotic function and it was induced in melanoma cells under conditions that promoted cell death.

Cardiac arrest: An interdisciplinary scoping review of the literature from 2019.

OBJECTIVES: The Interdisciplinary Cardiac Arrest Research Review (ICARE) group was formed in 2018 to conduct a systematic annual search of peer-reviewed literature relevant to cardiac arrest. Now in its second year, the goals of the review are to illustrate best practices in research and help reduce compartmentalization of knowledge by disseminating clinically relevant advances in the field of cardiac arrest across disciplines. METHODS: An electronic search of PubMed using keywords related to cardiac arrest was conducted. Title and abstracts retrieved by these searches were screened for relevance, classified by article type (original research or review), and sorted into 7 categories. Screened manuscripts underwent standardized scoring of overall methodological quality and impact on the categorized fields of study by reviewer teams lead by a subject-matter expert editor. Articles scoring higher than 99 percentiles by category-type were selected for full critique. Systematic differences between editors' and reviewers' scores were assessed using Wilcoxon signed-rank test. RESULTS: A total of 3348 articles were identified on initial search; of these, 1364 were scored after screening for relevance and deduplication, and forty-five underwent full critique. Epidemiology & Public Health represented 24% of fully reviewed articles with Prehospital Resuscitation, Technology & Care, and In-Hospital Resuscitation & Post-Arrest Care Categories both representing 20% of fully reviewed articles. There were no significant differences between editor and reviewer scoring. CONCLUSIONS: The sheer number of articles screened is a testament to the need for an accessible source calling attention to high-quality and impactful research and serving as a high-yield reference for clinicians and scientists seeking to follow the ever-growing body of cardiac arrest-related literature. This will promote further development of the unique and interdisciplinary field of cardiac arrest medicine.

Cardiac arrest: An interdisciplinary review of the literature from 2018.

OBJECTIVES: The Interdisciplinary Cardiac Arrest Research Review (ICARE) group was formed in 2018 to conduct a systematic annual search of peer-reviewed literature relevant to cardiac arrest (CA). The goals of the review are to illustrate best practices and help reduce knowledge silos by disseminating clinically relevant advances in the field of CA across disciplines. METHODS: An electronic search of PubMed using keywords related to CA was conducted. Title and abstracts retrieved by these searches were screened for relevancy, separated by article type (original research or review), and sorted into 7 categories. Screened manuscripts underwent standardized scoring of overall methodological quality and importance. Articles scoring higher than 99 percentiles by category-type were selected for full critique. Systematic differences between editors and reviewer scores were assessed using Wilcoxon signed-rank test. RESULTS: A total of 9119 articles were identified on initial search; of these, 1214 were scored after screening for relevance and deduplication, and 80 underwent full critique. Prognostication & Outcomes category comprised 25% and Epidemiology & Public Health 17.5% of fully reviewed articles. There were no differences between editor and reviewer scoring. CONCLUSIONS: The total number of articles demonstrates the need for an accessible source summarizing high-quality research findings to serve as a high-yield reference for clinicians and scientists seeking to absorb the ever-growing body of CA-related literature. This may promote further development of the unique and interdisciplinary field of CA medicine.

THAP5 is a human cardiac-specific inhibitor of cell cycle that is cleaved by the proapoptotic Omi/HtrA2 protease during cell death.

Omi/HtrA2 is a mitochondrial serine protease that has a dual function: while confined in the mitochondria, it promotes cell survival, but when released into the cytoplasm, it participates in caspase-dependent as well as caspase-independent cell death. To investigate the mechanism of Omi/HtrA2's function, we set out to isolate and characterize novel substrates for this protease. We have identified Thanatos-associated protein 5 (THAP5) as a specific interactor and substrate of Omi/HtrA2 in cells undergoing apoptosis. This protein is an uncharacterized member of the THAP family of proteins. THAP5 has a unique pattern of expression and is found predominantly in the human heart, although a very low expression is also seen in the human brain and muscle. THAP5 protein is localized in the nucleus and, when ectopically expressed, induces cell cycle arrest. During apoptosis, THAP5 protein is degraded, and this process can be blocked using a specific Omi/HtrA2 inhibitor, leading to reduced cell death. In patients with coronary artery disease, THAP5 protein levels substantially decrease in the myocardial infarction area, suggesting a potential role of this protein in human heart disease. This work identifies human THAP5 as a cardiac-specific nuclear protein that controls cell cycle progression. Furthermore, during apoptosis, THAP5 is cleaved and removed by the proapoptotic Omi/HtrA2 protease. Taken together, we provide evidence to support that THAP5 and its regulation by Omi/HtrA2 provide a new link between cell cycle control and apoptosis in cardiomyocytes.

The Association of Health Literacy With Preventable Emergency Department Visits: A Cross-sectional Study.

BACKGROUND: Policymakers argue that emergency department (ED) visits for conditions preventable with high-quality outpatient care contribute to waste in the healthcare system. However, access to ambulatory care is uneven, especially for vulnerable populations like minorities, the poor, and those with limited health literacy. The impact of limited health literacy on ED visits that are preventable with timely, high-quality ambulatory care is unknown. OBJECTIVE: The objective was to determine the association of health literacy with preventable ED visits. METHODS: We conducted an observational cross-sectional study of potentially preventable ED visits (outcome) among adults (≥18 years old) in an ED serving an urban community. We assessed health literacy (predictor) through structured interviews with the Rapid Estimate of Adult Literacy in Medicine (REALM). We recorded age, sex, race, employment, payer, marital and health status, and number of comorbidities through structured interviews or electronic record review. We identified potentially preventable ED visits in the 2 years before the index ED visit by applying Agency for Healthcare Research and Quality technical specifications to identify ambulatory care sensitive conditions using ED discharge diagnoses in hospital administrative data. We used Poisson regression to evaluate the number of preventable ED visits among patients with limited (REALM < 61) versus adequate (REALM ≥ 61) health literacy after adjusting for covariates. RESULTS: Of 1,201 participants, 709 (59%) were female, 370 (31%) were African American, mean age was 41.6 years, and 394 (33%) had limited health literacy. Of 4,444 total ED visits, 423 (9.5%) were potentially preventable. Of these, 260 (61%) resulted in hospital admission and 163 (39%) were treat and release. After covariates were adjusted for, patients with limited literacy had 2.3 (95% confidence interval [CI] = 1.7-3.1) times the number of potentially preventable ED visits resulting in hospital admission compared to individuals with adequate health literacy, 1.4 (95% CI = 1.0-2.0) times the number of treat-and-release visits, and 1.9 (95% CI = 1.5-2.4) times the number of total preventable ED visits. CONCLUSIONS: Our results suggest that the ED may be an important site to deploy universal literacy-sensitive precautions and to test literacy-sensitive interventions with the goal of reducing the burden of potentially preventable ED visits on patients and the healthcare system.