Abstract only
Introduction:
Extracorporeal cardiopulmonary resuscitation (ECPR) has been associated with improved outcomes compared to conventional CPR (CCPR) in children with underlying cardiac ...disease. There are limited data on ECPR survival outcomes in the non-cardiac population.
Hypothesis:
ECPR will be associated with improved survival to discharge in children without underlying cardiac disease with prolonged CPR.
Methods:
Retrospective cohort study using the AHA Get With The Guidelines® - Resuscitation registry of children (<18 years) without cardiac disease who received ≥30 minutes of CPR for in-hospital cardiac arrest between 2000-2020. Weighted propensity scores were used to balance ECPR and CCPR groups based on hospital and patient characteristics. Multivariable logistic regression incorporating these scores tested the association of ECPR with survival to discharge. A Bayesian logistic regression model was used to estimate the probability of a positive effect from ECPR. A secondary analysis explored temporal trends in ECPR relative to the index year of 2000.
Results:
Of 875 patients, 159 received ECPR and 716 received CCPR (median age 1 year, primary diagnosis respiratory insufficiency, median CPR duration 45 minutes for full cohort). Survival to discharge was similar between the ECPR group (21.4%) compared to the CCPR group (16.2%) in both the univariable analysis (p= 0.13) and the propensity-weighted multivariable logistic regression (aOR 1.44 CI 0.85-2.44, p= 0.173. The Bayesian model estimated an 85.1% probability of a positive effect of ECPR on survival to discharge. ECPR use increased over time (test for trend p<0.001).
Conclusion:
In children without cardiac disease who required ≥30 minutes of CPR, ECPR usage significantly increased in the last 20 years. Compared to CCPR, ECPR was not associated with a statistically significant increase in survival to discharge. However, a Bayesian model estimated weak evidence of a positive survival effect of ECPR.
The objective of this study was to determine the association of the use of extracorporeal cardiopulmonary resuscitation (ECPR) with survival to hospital discharge in pediatric patients with a ...noncardiac illness category. A secondary objective was to report on trends in ECPR usage in this population for 20 years.
Retrospective multicenter cohort study.
Hospitals contributing data to the American Heart Association's Get With The Guidelines-Resuscitation registry between 2000 and 2021.
Children (<18 yr) with noncardiac illness category who received greater than or equal to 30 minutes of cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest.
None.
Propensity score weighting balanced ECPR and conventional CPR (CCPR) groups on hospital and patient characteristics. Multivariable logistic regression incorporating these scores tested the association of ECPR with survival to discharge. A Bayesian logistic regression model estimated the probability of a positive effect from ECPR. A secondary analysis explored temporal trends in ECPR utilization. Of 875 patients, 159 received ECPR and 716 received CCPR. The median age was 1.0 interquartile range: 0.2-7.0 year. Most patients (597/875; 68%) had a primary diagnosis of respiratory insufficiency. Median CPR duration was 45 35-63 minutes. ECPR use increased over time ( p < 0.001). We did not identify differences in survival to discharge between the ECPR group (21.4%) and the CCPR group (16.2%) in univariable analysis ( p = 0.13) or propensity-weighted multivariable logistic regression (adjusted odds ratio 1.42 95% CI, 0.84-2.40; p = 0.19). The Bayesian model estimated an 85.1% posterior probability of a positive effect of ECPR on survival to discharge.
ECPR usage increased substantially for the last 20 years. We failed to identify a significant association between ECPR and survival to hospital discharge, although a post hoc Bayesian analysis suggested a survival benefit (85% posterior probability).
Students presenting with varying degrees of respiratory symptoms and distress occur commonly in the school setting. It is important to develop a differential diagnosis for respiratory distress, to ...initiate stabilization of the student with life-threatening symptoms, and to triage these students to an appropriate level of care (back to the classroom, home with their guardian with follow up at their primary health care provider's office, or directly to the closest emergency department via Emergency Medical Services). This article describes the initial assessment and management of a student presenting with respiratory distress.
Abstract
Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. Although advances in the treatment of ALL have resulted in a high cure rate for this disease, high-risk ALL is ...characterized by both resistance to conventional chemotherapy and a poor prognosis. The pathogenesis of high-risk ALL is still not understood. Casein Kinase II (CK2) is an oncogenic kinase that is overexpressed in both B-cell ALL (B-ALL) and T-cell ALL (T-ALL) and is associated with poor outcome. Inhibition of CK2 results in a strong therapeutic effect in a preclinical model of leukemia. However, the mechanism by which CK2 promotes oncogenesis in leukemia is unknown. Here, we studied how CK2 regulates expression of histone demethylase KDM5B in ALL. The KDM5B gene encodes a histone demethylase that regulates levels of histone modification H3K4me3 in leukemia. Molecular inhibition of CK2 using shRNA that targets the CK2 catalytic subunit resulted in transcriptional repression of KDM5B in ALL as evidenced by qRT-PCR. A similar effect was observed when leukemia cells were treated with the CK2 inhibitor CX-4945. Inhibition of CK2 resulted in reduced expression of KDM5B with an increase in the global cellular level of H3K4me3 as evidenced by Western blot. The use of quantitative chromatin immunoprecipitation (qChIP) showed that CK2 inhibition enhances DNA binding of the Ikaros tumor suppressor to the promoter of the KDM5B gene. Ikaros is a DNA-binding protein that regulates transcription of its target genes via chromatin remodeling. Loss of Ikaros function results in high-risk ALL. Serial qChIP analysis demonstrated that the increased Ikaros binding to the KDM5B promoter following CK2 inhibition is associated with an alteration of the epigenetic signature at the DNA region that surrounds the Ikaros binding site. Specifically, enhanced Ikaros binding results in increased occupancy of the H3K27me3 histone modification, along with a reduced occupancy of the H3K9ac histone modification at the KDM5B promoter. These results are consistent with the formation of heterochromatin and transcriptional repression. We tested the effect of CK2 inhibitors on Ikaros-mediated repression of KDM5B in primary, high-risk B-ALL cells that have a deletion of one Ikaros allele. Results showed that CK2 inhibition in high-risk B-ALL restores Ikaros binding to KDM5B promoter and represses KDM5B transcription. These data suggest that the inhibition of CK2 controls expression of KDM5B and the global H3K4me3 level in ALL by regulating the function of Ikaros as a transcriptional repressor of KDM5B. This presented data demonstrates the role of the CK2-Ikaros signaling axis in the regulation of both gene expression and the global epigenetic signature in ALL, and provide a mechanistic insight into the role of CK2 in the pathogenesis of ALL.
Citation Format: Morgann Loaec, Jonathon Payne, Elanora Dovat, Chunhua Song, Kimberly J. Payne, Sinisa Dovat. Epigenetic regulation of gene expression in high-risk B-cell acute lymphoblastic leukemia by Casein Kinase II. abstract. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4463.
To evaluate pediatric cardiopulmonary resuscitation (CPR) quality during intra-hospital transport to facilitate extracorporeal membrane oxygenation (ECMO)-CPR (ECPR). We compared chest compression ...(CC) rate, depth, and fraction (CCF) between the pre-transport and intra-transport periods.
Observational study of children <18 years with either in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA) who underwent transport between two care locations within the hospital for ECPR and who had CPR mechanics data available. Descriptive patient and arrest characteristics were summarized. The primary analysis compared pre- to intra-transport CC rate, depth, and fraction. A secondary analysis compared the proportion of pre- versus intra-transport 60-s epochs meeting guideline recommendations for rate (100–120/min), depth (≥4 cm for infants; ≥5 cm for children ≥1 year), and CCF (≥0.80).
Seven patients (four IHCA; three witnessed OHCA) met eligibility criteria. Six (86%) patients survived the event and two (28%) survived to hospital discharge. Median transport CPR duration was 7 IQR 5.5, 8.5 minutes. There were no differences in pre- vs. intra-transport CC rate (115 113, 118 vs. 118 114, 127 CCs/minute; p = 0.18), depth (3.2 2.7, 4.4 vs. 3.6 2.5, 4.6 cm; p = 0.50), or CCF (0.89 0.82, 0.90 vs. 0.92 0.79, 0.97; p = 0.31). Equivalent proportions of 60-s CPR epochs met guideline recommendations between pre- and intra-transport (rate: 66% vs. 57% p = 0.22; depth: 14% vs. 19% p = 0.39; CCF: 80% vs. 75% p = 0.43).
Pediatric CPR quality was maintained during intra-hospital patient transport, suggesting that it is reasonable for ECPR systems to incorporate patient transport to facilitate ECMO cannulation.
Students presenting with varying degrees of respiratory symptoms and distress occur commonly in the school setting. It is important to develop a differential diagnosis for respiratory distress, to ...initiate stabilization of the student with life-threatening symptoms, and to triage these students to an appropriate level of care (back to the classroom, home with their guardian with follow up at their primary health care provider’s office, or directly to the closest emergency department via Emergency Medical Services). This article describes the initial assessment and management of a student presenting with respiratory distress.
Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A ...(APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs.
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